A dysbiotic gut microbiome suppresses antibody mediated-protection against Vibrio cholerae.
Ontology highlight
ABSTRACT:
SUBMITTER: Macbeth JC
PROVIDER: S-EPMC8633975 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Evolutionary arms races are broadly prevalent among organisms including bacteria, which have evolved defensive strategies against various attackers. A common microbial aggression mechanism is the type VI secretion system (T6SS), a contact-dependent bacterial weapon used to deliver toxic effector proteins into adjacent target cells. Sibling cells constitutively express immunity proteins that neutralize effectors. However, less is known about factors that protect non-sibling bacteria from T6SS attacks independently of cognate immunity proteins. In this study, we observe that human Escherichia coli commensal strains sensitive to T6SS attacks from Vibrio cholerae are protected when co-cultured with glucose. We confirm that glucose does not impair V. cholerae T6SS activity. Instead, we find that cells lacking the cAMP receptor protein (CRP), which regulates expression of hundreds of genes in response to glucose, survive significantly better against V. cholerae T6SS attacks even in the absence of glucose. Finally, we show that the glucose-mediated T6SS protection varies with different targets and killers. Our findings highlight the first example of an extracellular small molecule modulating a genetically controlled response for protection against T6SS attacks. This discovery may have major implications for microbial interactions during pathogen-host colonization and survival of bacteria in environmental communities.
| S-EPMC7858629 | biostudies-literature
Project description:Zinc is an essential trace metal required for numerous cellular processes in all forms of life. In order to maintain zinc homeostasis, bacteria have developed several transport systems to regulate its uptake. In this study, we investigated zinc transport systems in the enteric pathogen Vibrio cholerae, the causative agent of cholera. Bioinformatic analysis predicts that two gene clusters, VC2081 to VC2083 (annotated as zinc utilization genes znuABC) and VC2551 to VC2555 (annotated as zinc-regulated genes zrgABCDE), are regulated by the putative zinc uptake regulator Zur. Using promoter reporter and biochemical assays, we confirmed that Zur represses znuABC and zrgABCDE promoters in a Zn(2+)-dependent manner. Under Zn(2+)-limiting conditions, we found that mutations in either the znuABC or zrgABCDE gene cluster affect bacterial growth, with znuABC mutants displaying a more severe growth defect, suggesting that both ZnuABC and ZrgABCDE are involved in Zn(2+) uptake and that ZnuABC plays the predominant role. Furthermore, we reveal that ZnuABC and ZrgABCDE are important for V. cholerae colonization in both infant and adult mouse models, particularly in the presence of other intestinal microbiota. Collectively, our studies indicate that these two zinc transporter systems play vital roles in maintaining zinc homeostasis during V. cholerae growth and pathogenesis.
| S-EPMC4567617 | biostudies-literature
Project description:Recent Ebola virus disease epidemics have highlighted the need for effective vaccines and therapeutics to prevent future outbreaks. Antibodies are clearly critical for control of this deadly disease; however, the specific mechanisms of action of protective antibodies have yet to be defined. In this Perspective we discuss the antibody features that correlate with in vivo protection during infection with Ebola virus, based on the results of a systematic and comprehensive study of antibodies directed against this virus. Although neutralization activity mediated by the Fab domains of the antibody is strongly correlated with protection, recruitment of immune effector functions by the Fc domain has also emerged as a complementary, and sometimes alternative, route to protection. For a subset of antibodies, Fc-mediated clearance and killing of infected cells seems to be the main driver of protection after exposure and mirrors observations in vaccination studies. Continued analysis of antibodies that achieve protection partially or wholly through Fc-mediated functions, the precise functions required, the intersection with specificity and the importance of these functions in different animal models is needed to identify and begin to capitalize on Fc-mediated protection in vaccines and therapeutics alike.
| S-EPMC6814399 | biostudies-literature
Project description:BackgroundCholera is an acute, diarrheal disease caused by Vibrio cholerae O1 or 139 that is associated with a high global burden.MethodsWe analyzed the estimated duration of immunity following cholera infection from available published studies. We searched PubMed and Web of Science for studies of the long-term immunity following cholera infection. We identified 22 eligible studies and categorized them as either observational, challenge, or serological.ResultsWe found strong evidence of protection at 3 years after infection in observational and challenge studies. However, serological studies show that elevated humoral markers of potential correlates of protection returned to baseline within 1 year. Additionally, a subclinical cholera infection may confer lower protection than a clinical one, as suggested by 3 studies that found that, albeit with small sample sizes, most participants with a subclinical infection from an initial challenge with cholera had a symptomatic infection when rechallenged with a homologous biotype.ConclusionsThis review underscores the need to elucidate potential differences in the protection provided by clinical and subclinical cholera infections. Further, more studies are warranted to bridge the gap between the correlates of protection and cholera immunity. Understanding the duration of natural immunity to cholera can help guide control strategies and policy.
| S-EPMC8136710 | biostudies-literature
Project description:Increasing evidence suggests that antibodies (Abs) can have protective roles in M. tuberculosis (Mtb) infection but knowledge of the most relevant protective antigens and epitopes in humans is limited. Using novel glycan arrays, we establish that human serum IgG induced against the M. tuberculosis (Mtb) capsular polysacharide arabinomannan (AM) in natural Mtb infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide (OS) motifs within AM and its functions between BCG vaccination and/or controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We show that anti-AM IgG from asymptomatic but not diseased individuals is protective, and provide data suggesting a role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our human data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.
2019-12-10 | GSE141679 | GEO
Project description:Vibrio cholerae O1 is one of two serogroups responsible for epidemic cholera, a severe watery diarrhea that occurs after the bacterium colonizes the human small intestine and secretes a potent ADP-ribosylating toxin. Immunity to cholera is associated with intestinal anti-lipopolysaccharide (LPS) antibodies, which are known to inhibit V. cholerae motility and promote bacterial cell-cell crosslinking and aggregation. Here we report that V. cholerae O1 classical and El Tor biotypes produce an extracellular matrix (ECM) when forcibly immobilized and agglutinated by ZAC-3 IgG, an intestinally-derived monoclonal antibody (MAb) against the core/lipid A region of LPS. ECM secretion, as demonstrated by crystal violet staining and scanning electron microscopy, occurred within 30 minutes of antibody exposure and peaked by 3 hours. Non-motile mutants of V. cholerae did not secrete ECM following ZAC-3 IgG exposure, even though they were susceptible to agglutination. The ECM was enriched in O-specific polysaccharide (OSP) but not Vibrio polysaccharide (VPS). Finally, we demonstrate that ECM production by V. cholerae in response to ZAC-3 IgG was associated with bacterial resistant to a secondary complement-mediated attack. In summary, we propose that V. cholerae O1, upon encountering anti-LPS antibodies in the intestinal lumen, secretes an ECM (or O-antigen capsule) possibly as a strategy to shield itself from additional host immune factors and to exit an otherwise inhospitable host environment.
| S-EPMC5749738 | biostudies-literature
Project description:It is clear that antibodies can play a pivotal role in preventing the transmission of HIV-1 and large efforts to identify an effective antibody-based vaccine to quell the epidemic. Shortly after HIV-1 was discovered as the cause of AIDS, the search for epitopes recognized by neutralizing antibodies became the driving strategy for an antibody-based vaccine. Neutralization escape variants were discovered shortly thereafter, and, after almost three decades of investigation, it is now known that autologous neutralizing antibody responses and their selection of neutralization resistant HIV-1 variants can lead to broadly neutralizing antibodies in some infected individuals. This observation drives an intensive effort to identify a vaccine to elicit broadly neutralizing antibodies. In contrast, there has been less systematic study of antibody specificities that must rely mainly or exclusively on other protective mechanisms, although non-human primate (NHP) studies as well as the RV144 vaccine trial indicate that non-neutralizing antibodies can contribute to protection. Here we propose a novel strategy to identify new epitope targets recognized by these antibodies for which viral escape is unlikely or impossible.
| S-EPMC5642910 | biostudies-literature
Project description:SignificanceIn a polymicrobial battlefield where different species compete for nutrients and colonization niches, antimicrobial compounds are the sword and shield of commensal microbes in competition with invading pathogens and each other. The identification of an Escherichia coli-produced genotoxin, colibactin, and its specific targeted killing of enteric pathogens and commensals, including Vibrio cholerae and Bacteroides fragilis, sheds light on our understanding of intermicrobial interactions in the mammalian gut. Our findings elucidate the mechanisms through which genotoxins shape microbial communities and provide a platform for probing the larger role of enteric multibacterial interactions regarding infection and disease outcomes.
| S-EPMC8931321 | biostudies-literature
Project description:Humans live in symbiosis with a diverse community of microorganisms, which has evolved to carry out many specific tasks that benefit the host, including protection against invading pathogens. Within the chemical diversity of the gastrointestinal tract, small molecules likely constitute chemical cues for the communication between the microbiota and pathogens. Therefore, we sought to investigate if molecules produced by the human gut microbiota show biological activity against the human pathogen Vibrio cholerae. To probe the effects of the gut metabolome on V. cholerae, we investigated its response to small-molecule extracts from human feces, from a complex bacterial community cultivated in vitro, and from culture supernatants of Enterocloster citroniae, Bacteroides thetaiotaomicron, and Bacteroides vulgatus. Using RNA sequencing, we determined the impact of the human gut metabolome on V. cholerae global gene expression. Among the genes downregulated in the presence of the fecal extract, the most overrepresented functional category was cell motility, which accounted for 39% of repressed genes. Repression of V. cholerae motility by the fecal extract was confirmed phenotypically, and E. citroniae extracts reproduced this phenotype. A complex in vitro microbial community led to increased motility, as did extracts from B. vulgatus, a species present in this community. Accordingly, mucin penetration was also repressed by fecal and E. citroniae extracts, suggesting that the phenotypes observed may have implications for host colonization. Together with previous studies, this work shows that small molecules from the gut metabolome may have a widespread, significant impact on microbe-microbe interactions established in the gut environment.
| S-EPMC8143261 | biostudies-literature
Project description:Background:Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood. Methods:We prospectively studied household contacts of patients with cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. Results:We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. Conclusion:These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.
| S-EPMC6047457 | biostudies-literature