Temperature is one of the most important factors in all living organisms for survival. Being a unicellular organism, bacterium requires sensitive sensing and defense mechanisms to tolerate changes in temperature. During a temperature shift, the structure and composition of various cellular molecules including nucleic acids, proteins, and membranes are affected. In addition, numerous genes are induced during heat or cold shocks to overcome the cellular stresses, which are known as heat- and cold-shock proteins. In this review, we describe the cellular phenomena that occur with temperature change and bacterial responses from a molecular perspective, mainly in Escherichia coli.

Bacterial cells are covered with various glycopolymers such as peptidoglycan (PG), lipopolysaccharides (LPS), teichoic acids, and capsules. Among these glycopolymers, PG assembly is the target of some of our most effective antibiotics, consistent with its essentiality and uniqueness to bacterial cells. Biosynthesis of other surface glycopolymers have also been acknowledged as potential targets for developing therapies to control bacterial infections, because of their importance for bacterial survival in the host environment. Moreover, biosynthesis of most surface glycopolymers are closely related to PG assembly because the same lipid carrier is shared for glycopolymer syntheses. In this review, I provide an overview of PG assembly and antibiotics that target this pathway. Then, I discuss the implications of a common lipid carrier being used for assembly of PG and other surface glycopolymers in antibiotic development.

The metal cofactors are essential for the function of many enzymes. The host restricts the metal acquisition of pathogens for their immunity and the pathogens have evolved many ways to obtain metal ions for their survival and growth. Salmonella enterica serovar Typhimurium also needs several metal cofactors for its survival, and manganese has been found to contribute to Salmonella pathogenesis. Manganese helps Salmonella withstand oxidative and nitrosative stresses. In addition, manganese affects glycolysis and the reductive TCA, which leads to the inhibition of energetic and biosynthetic metabolism. Therefore, manganese homeostasis is crucial for full virulence of Salmonella. Here, we summarize the current information about three importers and two exporters of manganese that have been identified in Salmonella. MntH, SitABCD, and ZupT have been shown to participate in manganese uptake. mntH and sitABCD are upregulated by low manganese concentration, oxidative stress, and host NRAMP1 level. mntH also contains a Mn2+-dependent riboswitch in its 5' UTR. Regulation of zupT expression requires further investigation. MntP and YiiP have been identified as manganese efflux proteins. mntP is transcriptionally activated by MntR at high manganese levels and repressed its activity by MntS at low manganese levels. Regulation of yiiP requires further analysis, but it has been shown that yiiP expression is not dependent on MntS. Besides these five transporters, there might be additional transporters that need to be identified.

Sialic acids consist of nine-carbon keto sugars that are commonly found at the terminal end of mucins. This positional feature of sialic acids contributes to host cell interactions but is also exploited by some pathogenic bacteria in evasion of host immune system. Moreover, many commensals and pathogens use sialic acids as an alternative energy source to survive within the mucus-covered host environments, such as the intestine, vagina, and oral cavity. Among the various biological events mediated by sialic acids, this review will focus on the processes necessary for the catabolic utilization of sialic acid in bacteria. First of all, transportation of sialic acid should be preceded before its catabolism. There are four types of transporters that are used for sialic acid uptake; the major facilitator superfamily (MFS), the tripartite ATP-independent periplasmic C4-dicarboxilate (TRAP) multicomponent transport system, the ATP binding cassette (ABC) transporter, and the sodium solute symporter (SSS). After being moved by these transporters, sialic acid is degraded into an intermediate of glycolysis through the well-conserved catabolic pathway. The genes encoding the catabolic enzymes and transporters are clustered into an operon(s), and their expression is tightly controlled by specific transcriptional regulators. In addition to these mechanisms, we will cover some researches about sialic acid utilization by oral pathogens.

Antibiotic treatment failure threatens our ability to control bacterial infections that can cause chronic diseases. Persister bacteria are a subpopulation of physiological variants that becomes highly tolerant to antibiotics. Membrane proteins play crucial roles in all living organisms to regulate cellular physiology. Although a diverse membrane component involved in persistence can result in antibiotic treatment failure, the regulations of antibiotic persistence by membrane proteins has not been fully understood. In this review, we summarize the recent advances in our understanding with regards to membrane proteins in Gram-negative bacteria as a regulator for antibiotic persistence, highlighting various physiological mechanisms in bacteria.

The active and inactive structures of the Escherichia coli cAMP receptor protein (CRP), a model bacterial transcription factor, are compared to generate a paradigm in the cAMP-induced activation of CRP. The resulting paradigm is shown to be consistent with numerous biochemical studies of CRP and CRP*, a group of CRP mutants displaying cAMP-free activity. The cAMP affinity of CRP is dictated by two factors: (i) the effectiveness of the cAMP pocket and (ii) the protein equilibrium of apo-CRP. How these two factors interplay in determining the cAMP affinity and cAMP specificity of CRP and CRP* mutants are discussed. Both the current understanding and knowledge gaps of CRP-DNA interactions are also described. This review ends with a list of several important CRP issues that need to be addressed in the future.

Pure cultivation of microbes is still limited by the challenges of microbial uncultivability, with most microbial strains unable to be cultivated under standard laboratory conditions. The experience accumulated from advanced techniques such as in situ cultivation has identified that microbial interactions exist in natural habitats but are absent in laboratory cultures. These microbial interactions are likely one of the key factors in isolating previously uncultured microbes. The need for better knowledge of the mechanisms operating in microbial interactions has led to various experiments that have utilized microbial interactions in different approaches to microbial cultivation. These new attempts to understand microbial interactions not only present a new perspective on microbial uncultivability but also provide an opportunity to access uncultured phylogenetically novel microbes with their potential biotechnology applications. In this review, we focus on studies of the mechanisms of microbial interaction where the growth of other microbes is affected. Additionally, we review some successful applications of microbial interactions in cultivation methods, an approach that can play an important role in the bioprospecting of untapped microbial resources.

Vaccines are one of the most powerful tools for preventing infectious diseases. To effectively fight pathogens, vaccines should induce potent and long-lasting immune responses that are specific to the pathogens. However, not all vaccines can induce effective immune responses, and the responses vary greatly among individuals and populations. Although several factors, such as age, host genetics, nutritional status, and region, affect the effectiveness of vaccines, increasing data have suggested that the gut microbiota is critically associated with vaccine-induced immune responses. In this review, I discuss how gut microbiota affects vaccine effectiveness based on the clinical and preclinical data, and summarize possible underlying mechanisms related to the adjuvant effects of microbiota. A better understanding of the link between vaccine-induced immune responses and the gut microbiota using high-throughput technology and sophisticated system vaccinology approaches could provide crucial insights for designing effective personalized preventive and therapeutic vaccination strategies.

Mycobacterium tuberculosis is the causative agent of tuberculosis. M. tuberculosis can survive in a dormant state within the granuloma, avoiding the host-mounting immune attack. M. tuberculosis bacilli in this state show increased tolerance to antibiotics and stress conditions, and thus the transition of M. tuberculosis to the nonreplicating dormant state acts as an obstacle to tuberculosis treatment. M. tuberculosis in the granuloma encounters hostile environments such as hypoxia, nitric oxide, reactive oxygen species, low pH, and nutrient deprivation, etc., which are expected to inhibit respiration of M. tuberculosis. To adapt to and survive in respiration-inhibitory conditions, it is required for M. tuberculosis to reprogram its metabolism and physiology. In order to get clues to the mechanism underlying the entry of M. tuberculosis to the dormant state, it is important to understand the mycobacterial regulatory systems that are involved in the regulation of gene expression in response to respiration inhibition. In this review, we briefly summarize the information regarding the regulatory systems implicated in upregulation of gene expression in mycobacteria exposed to respiration-inhibitory conditions. The regulatory systems covered in this review encompass the DosSR (DevSR) two-component system, SigF partner switching system, MprBA-SigE-SigB signaling pathway, cAMP receptor protein, and stringent response.

The disposal of sewage in significant quantities poses a health hazard to aquatic ecosystems. These effluents can contain a wide range of pathogens, making faecal contamination a leading source of waterborne diseases around the world. Yet monitoring bacteria or viruses in aquatic environments is time consuming and expensive. The standard indicators of faecal pollution all have limitations, including difficulty in determining the source due to lack of host specificity, poor connection with the presence of non-bacterial pathogens, or low environmental persistence. Innovative monitoring techniques are sorely needed to provide more accurate and targeted solutions. Viruses are a promising alternative to faecal indicator bacteria for monitoring, as they are more persistent in ambient water, more abundant in faeces, and are extremely host-specific. Given the range of viruses found in diverse contexts, it is not easy to find one "ideal" viral indicator of faecal pollution; however, several are of interest. In parallel, the ongoing development of molecular techniques coupled with metagenomics and bioinformatics should enable improved ways to detect faecal contamination using viruses. This review examines the evolution of faecal contamination monitoring with the following aims (i) to identify the characteristics of the main viral indicators of faecal contamination, including human enteric viruses, bacteriophages, CRESS and plant viruses, (ii) to assess how these have been used to monitor water pollution in recent years, (iii) to evaluate the reliability of recent detection methods of such viruses, and (iv) to tentatively determine which viruses may be most effective as markers of faecal pollution.

The global public health burden of bacterial antimicrobial resistance (AMR) is intensified by Gram-negative bacteria, which have an additional membrane, the outer membrane (OM), outside of the peptidoglycan (PG) cell wall. Bacterial two-component systems (TCSs) aid in maintaining envelope integrity through a phosphorylation cascade by controlling gene expression through sensor kinases and response regulators. In Escherichia coli, the major TCSs defending cells from envelope stress and adaptation are Rcs and Cpx, which are aided by OM lipoproteins RcsF and NlpE as sensors, respectively. In this review, we focus on these two OM sensors. β-Barrel assembly machinery (BAM) inserts transmembrane OM proteins (OMPs) into the OM. BAM co-assembles RcsF, the Rcs sensor, with OMPs, forming the RcsF-OMP complex. Researchers have presented two models for stress sensing in the Rcs pathway. The first model suggests that LPS perturbation stress disassembles the RcsF-OMP complex, freeing RcsF to activate Rcs. The second model proposes that BAM cannot assemble RcsF into OMPs when the OM or PG is under specific stresses, and thus, the unassembled RcsF activates Rcs. These two models may not be mutually exclusive. Here, we evaluate these two models critically in order to elucidate the stress sensing mechanism. NlpE, the Cpx sensor, has an N-terminal (NTD) and a C-terminal domain (CTD). A defect in lipoprotein trafficking results in NlpE retention in the inner membrane, provoking the Cpx response. Signaling requires the NlpE NTD, but not the NlpE CTD; however, OM-anchored NlpE senses adherence to a hydrophobic surface, with the NlpE CTD playing a key role in this function.

Tubulysins are bioactive secondary metabolites produced by myxobacteria that promote microtubule disassembly. Microtubules are required for protozoa such as Tetrahymena to form cilia and flagella. To study the role of tubulysins in myxobacteria, we co-cultured myxobacteria and Tetrahymena. When 4000 Tetrahymena thermophila and 5.0 × 108 myxobacteria were added to 1 ml of CYSE medium and co-cultured for 48 h, the population of T. thermophila increased to more than 75,000. However, co-culturing tubulysin-producing myxobacteria, including Archangium gephyra KYC5002, with T. thermophila caused the population of T. thermophila to decrease from 4000 to less than 83 within 48 h. Almost no dead bodies of T. thermophila were observed in the culture medium. Co-culturing of T. thermophila and the A. gephyra KYC5002 strain with inactivation of the tubulysin biosynthesis gene led to the population of T. thermophila increasing to 46,667. These results show that in nature, most myxobacteria are preyed upon by T. thermophila, but some myxobacteria prey on and kill T. thermophila using tubulysins. Adding purified tubulysin A to T. thermophila changed the cell shape from ovoid to spherical and caused cell surface cilia to disappear.

In this study, effects of ultrasonic treatment on Haematococcus pluvialis (H. pluvialis) were investigated. It has been confirmed that the ultrasonic stimulation acted as stress resources in the red cyst stage H. pluvialis cells containing astaxanthin, resulting in additional astaxanthin production. With the increase in production of astaxanthin, the average diameter of H. pluvialis cells increased accordingly. In addition, to determine how ultrasonic stimulation had an effect on the further biosynthesis of astaxanthin, genes related to astaxanthin synthesis and cellular ROS level were measured. As a result, it was confirmed that astaxanthin biosynthesis related genes and cellular ROS levels were increased, and thus ultrasonic stimulation acts as an oxidative stimulus. These results support the notion on the effect of the ultrasonic treatment, and we believe our novel approach based on the ultrasonic treatment would help to enhance the astaxanthin production from H. pluvialis.

The morphological switch from the yeast to hyphal form is a key virulence attribute of the opportunistic fungal pathogen, Candida albicans. Our recent report showed that deletion of the newly identified apoptotic factor, CaNma111 or CaYbh3, leads to hyperfilamentation and increased virulence in a mouse infection model. CaNma111 and CaYbh3 are homologs of the pro-apoptotic protease, HtrA2/Omi, and BH3-only protein, respectively. In this study, we examined the effects of CaNMA111 and CaYBH3 deletion mutations on the expression levels of the hypha-specific transcription factors, Cph1 (a hyphal activator), Nrg1 (a hyphal repressor), and Tup1 (a hyphal repressor). The protein levels of Nrg1 were decreased in Caybh3/Caybh3 cells while those of Tup1 were decreased in both Canma111/Canma111 and Caybh3/Caybh3 cells. These effects on Nrg1 and Tup1 proteins were retained during serum-induced filamentation and appear to explain the hyperfilamentation phenotypes of the CaNMA111 and CaYBH3 deletion mutants. Treatment with the apoptosis-inducing dose of farnesol decreased the Nrg1 protein levels in the wild-type strain and more evidently in Canma111/Canma111 and Caybh3/Caybh3 mutant strains. Together, our results suggest that CaNma111 and CaYbh3 are key regulators of Nrg1 and Tup1 protein levels in C. albicans.

In the post-genomic era, phylogenomics is a powerful and routinely-used tool to discover evolutionary relationships between microorganisms. Inferring phylogenomic trees by concatenating core gene sequences into a supermatrix is the standard method. The previously released up-to-date bacterial core gene (UBCG) tool provides a pipeline to infer phylogenomic trees using single-copy core genes for the Bacteria domain. In this study, we established up-to-date archaeal core gene (UACG), comprising 128 genes suitable for inferring archaeal phylogenomic trees. To test the gene set, we selected the Haloarcula genus and scrutinized its phylogeny. The phylogeny inferred using the UACG tool was consistent with the orthoANIu dendrogram, whereas the 16S rRNA gene phylogeny showed high intragenomic heterogeneity resulting in phylogenetic discrepancies. The software tool using the UACG set is available at https://www.ezbiocloud.net/tools/uacg .

Escherichia coli is a preferred strain for recombinant protein production, however, it is often plagued by phage infection during experimental studies and industrial fermentation. While the existing methods of obtaining phage-resistant strains by natural mutation are not efficient enough and time-consuming. Herein, a high-throughput method by combining Tn5 transposon mutation and phage screening was used to produce Escherichia coli BL21 (DE3) phage-resistant strains. Mutant strains PR281-7, PR338-8, PR339-3, PR340-8, and PR347-9 were obtained, and they could effectively resist phage infection. Meanwhile, they had good growth ability, did not contain pseudolysogenic strains, and were controllable. The resultant phage-resistant strains maintained the capabilities of producing recombinant proteins since no difference in mCherry red fluorescent protein expression was found in phage-resistant strains. Comparative genomics showed that PR281-7, PR338-8, PR339-3, and PR340-8 mutated in ecpE, nohD, nrdR, and livM genes, respectively. In this work, a strategy was successfully developed to obtain phage-resistant strains with excellent protein expression characteristics by Tn5 transposon mutation. This study provides a new reference to solve the phage contamination problem.

The existence of biogeography for microorganisms is a raising topic in ecology and researchers are employing better distinctions between single species, including the most rare ones, to reveal potential hidden patterns. An important volume of evidence supporting heterogeneous distributions for bacteria, archaea and protists is accumulating, and more recently a few efforts have targeted microscopic fungi. We propose an insight into this latter kingdom by looking at a group of soil nematode-trapping fungi whose species are well-known and easily recognizable. We chose a pure culture approach because of its reliable isolation procedures for this specific group. After morphologically and molecularly identifying all species collected from 2250 samples distributed in 228 locations across Yunnan province of China, we analyzed occurrence frequencies and mapped species, genera, and richness. Results showed an apparent cosmopolitan tendency for this group of fungi, including species richness among sites. However, only four species were widespread across the region, while non-random heterogeneous distributions were observed for the remaining 40 species, both in terms of statistical distribution of species richness reflected by a significant variance-to-mean ratio, as well as in terms of visually discernible spatial clusters of rare species and genera on the map. Moreover, several species were restricted to only one location, raising the question of whether endemicity exists for this microbial group. Finally, environmental heterogeneity showed a marginal contribution in explaining restricted distributions, suggesting that other factors such as geographical isolation and dispersal capabilities should be explored. These findings contribute to our understanding of the cryptic geographic distribution of microorganisms and encourage further research in this direction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence in 2019 led to global health crises and the persistent risk of viral mutations. To combat SARS-CoV-2 variants, researchers have explored new approaches to identifying potential targets for coronaviruses. This study aimed to identify SARS-CoV-2 inhibitors using drug repurposing. In silico studies and network pharmacology were conducted to validate targets and coronavirus-associated diseases to select potential candidates, and in vitro assays were performed to evaluate the antiviral effects of the candidate drugs to elucidate the mechanisms of the viruses at the molecular level and determine the effective antiviral drugs for them. Plaque and cytopathic effect reduction were evaluated, and real-time quantitative reverse transcription was used to evaluate the antiviral activity of the candidate drugs against SARS-CoV-2 variants in vitro. Finally, a comparison was made between the molecular docking binding affinities of fenofibrate and remdesivir (positive control) to conventional and identified targets validated from protein-protein interaction (PPI). Seven candidate drugs were obtained based on the biological targets of the coronavirus, and potential targets were identified by constructing complex disease targets and PPI networks. Among the candidates, fenofibrate exhibited the strongest inhibition effect 1 h after Vero E6 cell infection with SARS-CoV-2 variants. This study identified potential targets for coronavirus disease (COVID-19) and SARS-CoV-2 and suggested fenofibrate as a potential therapy for COVID-19.

Toxin-antitoxin (TA) systems are widespread in bacteria and archaea plasmids and genomes to regulate DNA replication, gene transcription, or protein translation. Higher eukaryotic and prokaryotic nucleotide-binding (HEPN) and minimal nucleotidyltransferase (MNT) domains are prevalent in prokaryotic genomes and constitute TA pairs. However, three gene pairs (MTH304/305, 408/409, and 463/464) of Methanothermobacter thermautotropicus ΔH HEPN-MNT family have not been studied as TA systems. Among these candidates, our study characterizes the MTH463/MTH464 TA system. MTH463 expression inhibited Escherichia coli growth, whereas MTH464 did not and blocked MTH463 instead. Using site-directed MTH463 mutagenesis, we determined that amino acids R99G, H104A, and Y106A from the R[ɸX]4-6H motif are involved with MTH463 cell toxicity. Furthermore, we established that purified MTH463 could degrade MS2 phage RNA, whereas purified MTH464 neutralized MTH463 activity in vitro. Our results indicate that the endonuclease toxin MTH463 (encoding a HEPN domain) and its cognate antitoxin MTH464 (encoding the MNT domain) may act as a type II TA system in M. thermautotropicus ΔH. This study provides initial and essential information studying TA system functions, primarily archaea HEPN-MNT family.

Fibroblast growth factor 11 (FGF11) is a member of the intracellular FGF family, which shows different signal transmission compared with other FGF superfamily members. The molecular function of FGF11 is not clearly understood. In this study, we identified the inhibitory effect of FGF11 on hepatitis B virus (HBV) gene expression through transcriptional suppression. FGF11 decreased the mRNA and protein expression of HBV genes in liver cells. While the nuclear receptor FXRα1 increased HBV promoter transactivation, FGF11 decreased the FXRα-mediated gene induction of the HBV promoter by the FXRα agonist. Reduced endogenous levels of FXRα by siRNA and the dominant negative mutant protein (aa 1-187 without ligand binding domain) of FXRα expression indicated that HBV gene suppression by FGF11 is dependent on FXRα inhibition. In addition, FGF11 interacts with FXRα protein and reduces FXRα protein stability. These results indicate that FGF11 inhibits HBV replicative expression through the liver cell-specific transcription factor, FXRα, and suppresses HBV promoter activity. Our findings may contribute to the establishment of better regimens for the treatment of chronic HBV infections by including FGF11 to alter the bile acid mediated FXR pathway.

Norovirus is one of the leading causes of acute gastroenteritis outbreaks worldwide. This study aimed to identify the epidemiological characteristics of norovirus outbreaks and to provide evidence for public health entities. Specimens and epidemiological survey data were collected to determine if there were differences in the attack rate of norovirus in terms of the year, season, transmission route, exposure setting, and region and to determine whether there were relationships between the reporting interval, the number of illnesses in a single outbreak and the duration of the outbreak. Norovirus outbreaks were reported throughout the year, with seasonal characteristics (i.e., high rates in spring and winter). Among all regions in Shenyang with the exception of Huanggu and Liaozhong, norovirus outbreaks had been reported, and the primary genotype was GII.2[P16]. Vomiting was the most common symptom. The main places of occurrence were childcare institutions and schools. The person-to-person route was the main transmission route. The median duration of norovirus was 3 days (IQR [interquartile range]: 2-6 days), the median reporting interval was 2 days (IQR: 1-4 days), the median number of illnesses in a single outbreak was 16 (IQR: 10-25); there was a positive correlation between these parameters. Norovirus surveillance and genotyping studies still need to be further strengthened to increase knowledge regarding the pathogens and their variant characteristics, to better characterize the patterns of norovirus outbreaks and to provide information for outbreak prevention. Norovirus outbreaks should be detected, reported and handled early. Public health entities and the government should develop corresponding measures for different seasons, transmission routes, exposure settings, and regions.

Microbial communities played a vital role in maintaining homeostasis of ocular surface. However, no studies explored the myopia-associated conjunctiva microbiota changes until now. In this study, conjunctival sac swab specimens were collected from 12 eyes of low myopia (LM), and 14 eyes of high myopia (HM) patients. The V3-V4 region of the 16S rRNA gene was amplified and then sequenced. Statistical analysis was performed to investigate differences in the taxonomy and diversity between two groups. Compared to LM, higher Ocular Surface Disease Index (OSDI) scores were observed in HM group. The Shannon index of the HM was lower than that of the LM group (P = 0.017). Principle coordinate analysis and Partial Least Squares Discrimination Analysis showed distinct microbiome composition between two groups. At the phylum level, there were higher relative abundances of Proteobacteria (68.27% vs 38.51%) and lower abundances of Actinobacteria (3.71% vs 9.19%) in HM, compared to LM group (P = 0.031, 0.010, respectively). At the genus level, the abundances of Acinetobacter in HM (18.16%) were significantly higher than the LM (6.52%) group (P = 0.011). Actinobacteria levels were negatively correlated with the myopic spherical equivalent and OSDI scores. Moreover, positive correlations were found between Proteobacteria levels and OSDI scores, Acinetobacter levels were positively correlated with myopic spherical equivalent and OSDI scores. In conclusion, HM Patients have bacterial microbiota imbalance in the conjunctival sac, compared with LM patients. Proteobacteria, Actinobacteria, Acinetobacter may play roles in the HM associated ocular surface irritation.

Basal stem rot incidence caused by a white-rot fungus, Ganoderma boninense, is the major disease of oil palm in Southeast Asia. The rate of disease transmission and host damage are affected by variations in pathogen aggressiveness. Several other studies have used the disease severity index (DSI) to determine G. boninense aggressiveness levels while verifying disease using a culture-based method, which might not provide accurate results or be feasible in all cases. To differentiate G. boninense aggressiveness, we employed the DSI and vegetative growth measurement of infected oil palm seedlings. Disease confirmation was performed through scanning electron microscopy and molecular identification of fungal DNA from both infected tissue and fungi isolated from Ganoderma selective medium. Two-month-old oil palm seedlings were artificially inoculated with G. boninense isolates (2, 4A, 5A, 5B, and 7A) sampled from Miri (Lambir) and Mukah (Sungai Meris and Sungai Liuk), Sarawak. The isolates were categorized into three groups: highly aggressive (4A and 5B), moderately aggressive (5A and 7A), and less aggressive (2). Isolate 5B was identified as the most aggressive, and it was the only one to result in seedling mortality. Out of the five vegetative growth parameters measured, only the bole size between treatments was not affected. The integration of both conventional and molecular approaches in disease confirmation allows for precise detection.

Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.

Silver nanoparticles (AgNPs) exhibit strong antibacterial activity and do not easily induce drug resistance; however, the poor stability and biocompatibility in solution limit their widespread application. In this study, AgNPs were modified with Polygonatum sibiricum Polysaccharide (PSP) to synthesize PSP@AgNPs with good stability, biocompatibility, and antibacterial activity. When PSP@AgNP synthesis was performed under a reaction time of 70 min, a reaction temperature of 35 °C, and an AgNO3-to-PSP volume ratio of 1:1, the synthesized PSP@AgNPs were more regular and uniform than AgNPs, and their particle size was around 10 nm. PSP@AgNPs exhibited lower cytotoxicity and hemolysis, and stronger bacteriostatic activity. PSP@AgNPs damage the integrity and internal structure of cells, resulting in the leakage of intracellular nucleic acids and proteins. The rate of cell membrane damage in Escherichia coli and Staphylococcus aureus treated with PSP@AgNPs increased by 38.52% and 43.75%, respectively, compared with that of AgNPs. PSP@AgNPs inhibit the activities of key enzymes related to antioxidant, energy and substance metabolism in cells. The inhibitory effects on the activities of superoxide dismutase (SOD), catalase (CAT), adenosine triphosphate enzyme (ATPase), malate dehydrogenase (MDH), and succinate dehydrogenase (SDH) in E. coli and S. aureus cells were significantly higher than those of AgNPs. In addition, compared with AgNPs, PSP@AgNPs promote faster healing of infected wounds. Therefore, PSP@AgNPs represent potential antibacterial agents against wound infections.

Soil-borne diseases are closely related to rhizosphere microecosystem. While, plant species and genotypes are important factors affected rhizosphere microecosystem. In this study, the rhizosphere soil microbial community and metabolites of susceptible and resistant tobacco cultivars were investigated. The results showed that there were significant differences in the rhizosphere microbial community and metabolites between susceptible cultivar Yunyan87 and resistant cultivar Fandi3. Furthermore, the rhizosphere soil of Fandi3 showed a higher microbial diversity than that of Yunyan87. The abundance of R. solanacearum was much higher in the rhizosphere soil of Yunyan87 than in the rhizosphere soil of Fandi3, resulting in a higher disease incidence and index. While the abundance of beneficial bacteria in the rhizosphere soil of Fandi3 were higher than that of Yunyan87. Additionally, there were significant differences in metabolites between Yunyan87 and Fandi3 cultivars, and 4-hydroxybenzaldehyde, 3-hydroxy-4-methoxybenzoic acid, vamillic aldehyde, benzoic acid, 4-hydroxybenzyl alcohol, p-hydroxybenzoic acid and phthalic acid were notably high in Yunyan87. Redundancy analysis (RDA) indicated that the rhizosphere microbial community of Fandi3 and Yunyan87 were highly correlated with various environmental factors and metabolites. Overall, susceptible and resistant tobacco cultivars had different impact on rhizosphere microbial community and metabolites. The results expand our understanding of the roles of tobacco cultivars in plant-micro-ecosystem interactions, and provide a basis for the control of tobacco bacterial wilt.

Lipolanthine is a subclass of lanthipeptide that has the modification of lipid moiety at the N-terminus. A cryptic biosynthetic gene cluster comprising four genes (sinA, sinKC, sinD, and sinE) involved in the biosynthesis of lipolanthine was identified in the genome of an actinobacterium Sinosporangium siamense. Heterologous coexpression of a precursor peptide coding gene sinA and lanthipeptide synthetase coding gene sinKC in the host Escherichia coli strain BL21(DE3) resulted in the synthesis of a new lanthipeptide, sinosporapeptin. It contained unusual amino acids, including one labionin and two dehydrobutyrine residues, as determined using NMR and MS analyses. Another coexpression experiment with two additional genes of decarboxylase (sinD) and N-acetyl transferase (sinE) resulted in the production of a lipolanthine-like modified sinosporapeptin.

The name Flavihumibacter fluminis Park et al. 2022, which was effectively published but invalidated, is an illegitimate homonymic epithet of Flavihumibacter fluminis Guo et al. 2023. The low 16S rRNA gene sequence similarity and genomic relatedness between the type strains IMCC34837T and RY-1T of the two homonymic species indicated that they are different species. To avoid further confusion, we propose a new name Flavihumibacter fluvii sp. nov. to replace the effectively published but invalidated homonymic epithet Flavihumibacter fluminis Park et al. 2022.

Norovirus (NoV) is the most common viral cause of acute gastroenteritis worldwide. Vitamin A has demonstrated the potential to protect against gastrointestinal infections. However, the effects of vitamin A on human norovirus (HuNoV) infections remain poorly understood. This study aimed to investigate how vitamin A administration affects NoV replication. We demonstrated that treatment with retinol or retinoic acid (RA) inhibited NoV replication in vitro based on their effects on HuNoV replicon-bearing cells and murine norovirus-1 (MNV-1) replication in murine cells. MNV replication in vitro showed significant transcriptomic changes, which were partially reversed by retinol treatment. RNAi knockdown of CCL6, a chemokine gene that was downregulated by MNV infection but upregulated by retinol administration, resulted in increased MNV replication in vitro. This suggested a role of CCL6 in the host response to MNV infections. Similar gene expression patterns were observed in the murine intestine after oral administration of RA and/or MNV-1.CW1. CCL6 directly decreased HuNoV replication in HG23 cells, and might indirectly regulate the immune response against NoV infection. Finally, relative replication levels of MNV-1.CW1 and MNV-1.CR6 were significantly increased in CCL6 knockout RAW 264.7 cells. This study is the first to comprehensively profile transcriptomes in response to NoV infection and vitamin A treatment in vitro, and thus may provide new insights into dietary prophylaxis and NoV infections.

Ulcerative colitis, a major form of inflammatory bowel disease (IBD) associated with chronic colonic inflammation, may be induced via overreactive innate and adaptive immune responses. Restoration of gut microbiota abundance and diversity is important to control the pathogenesis. Lactobacillus spp., well-known probiotics, ameliorate IBD symptoms via various mechanisms, including modulation of cytokine production, restoration of gut tight junction activity and normal mucosal thickness, and alterations in the gut microbiota. Here, we studied the effects of oral administration of Lactobacillus rhamnosus (L. rhamnosus) KBL2290 from the feces of a healthy Korean individual to mice with DSS-induced colitis. Compared to the dextran sulfate sodium (DSS) + phosphate-buffered saline control group, the DSS + L. rhamnosus KBL2290 group evidenced significant improvements in colitis symptoms, including restoration of body weight and colon length, and decreases in the disease activity and histological scores, particularly reduced levels of pro-inflammatory cytokines and an elevated level of anti-inflammatory interleukin-10. Lactobacillus rhamnosus KBL2290 modulated the levels of mRNAs encoding chemokines and markers of inflammation; increased regulatory T cell numbers; and restored tight junction activity in the mouse colon. The relative abundances of genera Akkermansia, Lactococcus, Bilophila, and Prevotella increased significantly, as did the levels of butyrate and propionate (the major short-chain fatty acids). Therefore, oral L. rhamnosus KBL2290 may be a useful novel probiotic.

The Fusarium graminearum species complex (FGSC) can produce various mycotoxins and is a major concern for food quantity and quality worldwide. In this study, we determined the effects of water activity (aw), temperature, incubation time and their interactions on mycotoxin accumulation and the expression levels of biosynthetic genes in FGSC strains from maize samples in China. The highest deoxynivalenol (DON), 3-acetyldeoxynivalenol(3ADON) and 15-acetyldeoxynivalenol (15ADON) levels of the F. boothii and F. graminearum strains were observed at 0.98 aw/30 °C or 0.99 aw/25 °C. F. asiaticum and F. meridionale reached maximum nivalenol (NIV) and 4-acetylnivalenol (4ANIV) contents at 0.99 aw and 30 °C. With the extension of the incubation time, the concentrations of DON and NIV gradually increased, while those of their derivatives decreased. F. boothii, F. meridionale and one F. asiaticum strain had the highest zearalenone (ZEN) values at 0.95 aw and 25 °C, while the optimum conditions for the other F. asiaticum strain and F. graminearum were 0.99 aw and 30 °C. Four genes associated with trichothecene and zearalenone synthesis were significantly induced under higher water stress in the early stage of production. The results indicated independence of mycotoxin production and gene expression, as maximum amounts of these toxic metabolites were observed at higher aw in most cases. This study provides useful information for the monitoring and prevention of such toxins entering the maize production chain.

Ship biofouling is one of the main vectors for the introduction and global spread of non-indigenous organisms. Diatoms were the early colonizers of ship hulls; however, their community composition on ships is poorly understood. Herein, we investigated the diatom community on the hull samples collected from two Korean research vessels Isabu (IRV) and Onnuri (ORV) on September 2 and November 10, 2021, respectively. IRV showed low cell density (345 cells/cm2) compared to ORV (778 cells/cm2). We morphologically identified more than 15 species of diatoms from the two research vessels (RVs). The microalgae in both RVs were identified as Amphora, Cymbella, Caloneis, Halamphora, Navicula, Nitzschia, and Plagiogramma. Of them, the genus Halamphora was found to be predominant. However, both RVs had a varied dominant species with a significant difference in body size; Halamphora oceanica dominated at IRV, and Halamphora sp. at ORV, respectively. Molecular cloning showed similar results to morphological analysis, in which Halamphora species dominated in both RVs. The hull-attached species were distinct from species found in the water column. These results revealed diatoms communities that are associated with ship hull-fouling at an early stage of biofilm formation. Moreover, ships arriving from different regions could show some variation in species composition on their hull surfaces, with the potential for non-indigenous species introduction.

Two novel Gram-stain-positive, aerobic, non-motile, and yellow-pigmented, irregular rod-shaped bacteria (JY.X269 and JY.X270T) were isolated from the near-surface sediments of river in Qinghai Province, P. R. China (32°37'13″N, 96°05'37″E) in July 2019. Both strains were shown to grow at 15-35 °C and pH 7.0-10.0, and in the presence of 0-6.0% (w/v) NaCl. The 16S rRNA gene sequence analysis showed that the isolates were closely related to Ornithinimicrobium cavernae CFH 30183 T (98.6-98.8% 16S rRNA gene sequence similarity), O. ciconiae H23M54T (98.5-98.6%) and O. murale 01-Gi-040T (98.3-98.5%). The phylogenetic and phylogenomic trees based on the 16S rRNA gene and 537 core gene sequences, respectively, revealed that the two strains formed a distinct cluster with the above three species. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between our two isolates (JY.X269 and JY.X270T) and other Ornithinimicrobium species were within the ranges of 19.0-23.9% and 70.8-80.4%, respectively, all below the respective recommended 70.0% and 95-96% cutoff point. Furthermore, the major cellular fatty acids (> 10.0%) of strains JY.X269 and JY.X270T were iso-C15:0, iso-C16:0, and summed feature 9. Strain JY.X270T contained MK-8(H4) and ornithine as the predominant menaquinone and diagnostic diamino acid component within the cell wall teichoic acids. β-cryptoxanthin (C40H56O) can be extracted from strain JY.X270T, and its content is 6.3 µg/ml. Based on results from the phylogenetic, chemotaxonomic, and phenotypic analyses, the two strains could be classified as a novel species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium cryptoxanthini sp. nov. is proposed (type strain JY.X270T = CGMCC 1.19147T = JCM 34882T).

We previously showed that both high-mobility group box-1 (HMGB1) and natural killer (NK) cells contribute to respiratory syncytial virus (RSV)-induced persistent airway inflammation and airway hyperresponsiveness (AHR). Meanwhile, Chemokine (C-X-C motif) ligand 12 (CXCL12) and its specific receptor (chemokine receptor 4, CXCR4) play important roles in recruitment of immune cells. CXCL12 has been reported to form a complex with HMGB1 that binds to CXCR4 and increases inflammatory cell migration. The relationship between HMGB1, NK cells and chemokines in RSV-infected model remains unclear. An anti-HMGB1 neutralizing antibody and inhibitor of CXCR4 (AMD3100) was administered to observe changes of NK cells and airway disorders in nude mice and BALB/c mice. Results showed that the mRNA expression and protein levels of HMGB1 were elevated in late stage of RSV infection and persistent airway inflammation and AHR were diminished after administration of anti-HMGB1 antibodies, with an associated significant decrease in CXCR4+ NK cells. In addition, CXCL12 and CXCR4 were reduced after HMGB1 blockade. Treatment with AMD3100 significantly suppressed the recruitment of NK cells and alleviated the airway disorders. Thus, CXCL12/CXCR4 axis is involved in the recruitment of NK cells by HMGB1, contributing to persistent airway inflammation and AHR during the late stage of RSV infection.

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that can infect humans in contact with infected pigs or their byproducts. It can employ different types of genes to defend against oxidative stress and ensure its survival. The thioredoxin (Trx) system is a key antioxidant system that contributes adversity adaptation and pathogenicity. SS2 has been shown to encode putative thioredoxin genes, but the biological roles, coding sequence, and underlying mechanisms remains uncharacterized. Here, we demonstrated that SSU05_0237-ORF, from a clinical SS2 strain, ZJ081101, encodes a protein of 104 amino acids with a canonical CGPC active motif and an identity 70-85% similar to the thioredoxin A (TrxA) in other microorganisms. Recombinant TrxA efficiently catalyzed the thiol-disulfide oxidoreduction of insulin. The deletion of TrxA led to a significantly slow growth and markedly compromised tolerance of the pathogen to temperature stress, as well as impaired adhesion ability to pig intestinal epithelial cells (IPEC-J2). However, it was not involved in H2O2 and paraquat-induced oxidative stress. Compared with the wild-type strain, the ΔTrxA strain was more susceptible to killing by macrophages through increasing NO production. Treatment with TrxA mutant strain also significantly attenuated cytotoxic effects on RAW 264.7 cells by inhibiting inflammatory response and apoptosis. Knockdown of pentraxin 3 in RAW 264.7 cells was more vulnerable to phagocytic activity, and TrxA promoted SS2 survival in phagocytic cells depending on pentraxin 3 activity compared with the wild-type strain. Moreover, a co-inoculation experiment in mice revealed that TrxA mutant strain is far more easily cleared from the body than the wild type strain in the period from 8-24 h, and exhibits significantly attenuated oxidative stress and liver injury. In summary, we reveal the important role of TrxA in the pathogenesis of SS2.

Three novel bacterial strains, 321T, 335T, and 353T, were isolated from the intestines of Aegosoma sinicum larvae collected from Paju-Si, South Korea. The strains were Gram-negative, obligate aerobe and had rod-shaped cells with a single flagellum. The three strains belonged to the genus Luteibacter in the family Rhodanobacteraceae and shared < 99.2% similarity in their 16S rRNA gene sequence and < 83.56% similarity in thier whole genome sequence. Strains 321T, 335T, and 353T formed a monophyletic clade with Luteibacter yeojuensis KACC 11405T, L. anthropi KACC 17855T, and L. rhizovicinus KACC 12830T, with sequence similarities of 98.77-98.91%, 98.44-98.58%, and 97.88-98.02%, respectively. Further genomic analyses, including the construction of the Up-to-date Bacterial Core Gene (UBCG) tree and assessment of other genome-related indices, indicated that these strains were novel species belonging to the genus Luteibacter. All three strains contained ubiquinone Q8 as their major isoprenoid quinone and iso-C15:0 and summed feature 9 (C16:0 10-methyl and/or iso-C17:1 ω9c) as their major cellular fatty acids. Phosphatidylethanolamine and diphosphatidylglycerol were the major polar lipids in all the strains. The genomic DNA G + C contents of strains 321T, 335T, and 353T were 66.0, 64.5, and 64.5 mol%, respectively. Based on multiphasic classification, strains 321T, 335T, and 353T were classified into the genus Luteibacter as the type strains of novel species, for which the names Luteibacter aegosomatis sp. nov., Luteibacter aegosomaticola sp. nov., and Luteibacter aegosomatissinici sp. nov. are proposed, respectively.

Eleven bacterial strains were isolated from freshwater environments and identified as Flavobacterium based on 16S rRNA gene sequence analyses. Complete genome sequences of the 11 strains ranged from 3.45 to 5.83 Mb with G + C contents of 33.41-37.31%. The average nucleotide identity (ANI) values showed that strains IMCC34515T and IMCC34518 belonged to the same species, while the other nine strains represented each separate species. The ANI values between the strains and their closest Flavobacterium species exhibited ≤ 91.76%, indicating they represent each novel species. All strains had similar characteristics such as being Gram-stain-negative, rod-shaped, and contained iso-C15:0 as the predominant fatty acid, menaquinone-6 as the respiratory quinone, and phosphatidylethanolamine and aminolipids as major polar lipids. Genomic, phylogenetic, and phenotypic characterization confirmed that the 11 strains were distinct from previously recognized Flavobacterium species. Therefore, Flavobacterium praedii sp. nov. (IMCC34515T = KACC 22282 T = NBRC 114937 T), Flavobacterium marginilacus sp. nov. (IMCC34673T = KACC 22284 T = NBRC 114940 T), Flavobacterium aestivum sp. nov. (IMCC34774T = KACC 22285 T = NBRC 114941 T), Flavobacterium flavigenum sp. nov. (IMCC34775T = KACC 22286 T = NBRC 114942 T), Flavobacterium luteolum sp. nov. (IMCC34776T = KACC 22287 T = NBRC 114943 T), Flavobacterium gelatinilyticum sp. nov. (IMCC34777T = KACC 22288 T = NBRC 114944 T), Flavobacterium aquiphilum sp. nov. (IMCC34779T = KACC 22289 T = NBRC 114945 T), Flavobacterium limnophilum sp. nov. (IMCC36791T = KACC 22290 T = NBRC 114947 T), Flavobacterium lacustre sp. nov. (IMCC36792T = KACC 22291 T = NBRC 114948 T), and Flavobacterium eburneipallidum sp. nov. (IMCC36793T = KACC 22292 T = NBRC 114949 T) are proposed as novel species.

Subtercola boreus K300T is a novel psychrophilic strain that was isolated from permanently cold groundwater in Finland and has also been found in several places in Antarctica including lake, soil, and rocks. We performed genomic and transcriptomic analyses of 5 strains from Antarctica and a type strain to understand their adaptation to different environments. Interestingly, the isolates from rocks showed a low growth rate and smaller genome size than strains from the other isolation sources (lake, soil, and groundwater). Based on these habitat-dependent characteristics, the strains could be classified into two ecotypes, which showed differences in energy production, signal transduction, and transcription in the clusters of orthologous groups of proteins (COGs) functional category. In addition, expression pattern changes revealed differences in metabolic processes, including uric acid metabolism, DNA repair, major facilitator superfamily (MFS) transporters, and xylose degradation, depending on the nutritional status of their habitats. These findings provide crucial insights into the environmental adaptation of bacteria, highlighting genetic diversity and regulatory mechanisms that enable them to thrive in the cryosphere.