scholarly journals Characterization of the Immune Response to Vibrio cholerae Infection in a Natural Host Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Dustin A. Farr ◽  
Dhrubajyoti Nag ◽  
Jeffrey H. Withey
Keyword(s):  
Immune Response ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Natural Host ◽  
Zebrafish Model ◽  
Mucin Production ◽  
Immunological Markers ◽  
Contaminated Food ◽  
Life Threatening ◽  
El Tor

The gram-negative bacterium Vibrio cholerae causes the life-threatening diarrheal disease cholera, which is spread through the ingestion of contaminated food or water. Cholera epidemics occur largely in developing countries that lack proper infrastructure to treat sewage and provide clean water. Numerous vertebrate fish species have been found to be natural V. cholerae hosts. Based on these findings, zebrafish (Danio rerio) have been developed as a natural host model for V. cholerae. Diarrheal symptoms similar to those seen in humans are seen in zebrafish as early as 6 hours after exposure. Our understanding of basic zebrafish immunology is currently rudimentary, and no research has been done to date exploring the immune response of zebrafish to V. cholerae infection. In the present study, zebrafish were infected with either pandemic El Tor or non-pandemic, environmental V. cholerae strains and select immunological markers were assessed to determine cellular immunity and humoral immunity. Significant increases in the gene expression of two transcription factors, T-bet and GATA3, were observed in response to infection with both V. cholerae strains, as were levels of mucosal related antibodies. Additionally, the cytokine IL-13 was shown to be significantly elevated and paralleled the mucin output in zebrafish excretions, strengthening our knowledge of IL-13 induced mucin production in cholera. The data presented here further solidify the relevancy of the zebrafish model in studying V. cholerae, as well as expanding its utility in the field of cholera immunology.

scholarly journals Zebrafish as a Natural Host Model for Vibrio cholerae Colonization and Transmission

2013 ◽  
Vol 80 (5) ◽  
pp. 1710-1717 ◽  
Author(s):  
Donna L. Runft ◽  
Kristie C. Mitchell ◽  
Basel H. Abuaita ◽  
Jonathan P. Allen ◽  
Sarah Bajer ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Intestinal Tract ◽  
Diarrheal Disease ◽  
Close Contact ◽  
Natural Habitat ◽  
Natural Host ◽  
Aquatic Life ◽  
Content Type ◽  
Environmental Survival ◽  
El Tor

ABSTRACTThe human diarrheal disease cholera is caused by the aquatic bacteriumVibrio cholerae.V. choleraein the environment is associated with several varieties of aquatic life, including insect egg masses, shellfish, and vertebrate fish. Here we describe a novel animal model forV. cholerae, the zebrafish. PandemicV. choleraestrains specifically colonize the zebrafish intestinal tract after exposure in water with no manipulation of the animal required. Colonization occurs in close contact with the intestinal epithelium and mimics colonization observed in mammals. Zebrafish that are colonized byV. choleraetransmit the bacteria to naive fish, which then become colonized. Striking differences in colonization betweenV. choleraeclassical and El Tor biotypes were apparent. The zebrafish natural habitat in Asia heavily overlaps areas where cholera is endemic, suggesting that zebrafish andV. choleraeevolved in close contact with each other. Thus, the zebrafish provides a natural host model for the study ofV. choleraecolonization, transmission, and environmental survival.

scholarly journals Neutrophils Are Essential for Containment of Vibrio cholerae to the Intestine during the Proinflammatory Phase of Infection

2012 ◽  
Vol 80 (8) ◽  
pp. 2905-2913 ◽  
Author(s):  
Jessica Queen ◽  
Karla J. Fullner Satchell
Keyword(s):  
Immune Response ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Innate Immune ◽  
Infection Model ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Live Attenuated Vaccine ◽  
Content Type

ABSTRACTCholera is classically considered a noninflammatory diarrheal disease, in comparison to invasive enteric organisms, although there is a low-level proinflammatory response during early infection withVibrio choleraeand a strong proinflammatory reaction to live attenuated vaccine strains. Using an adult mouse intestinal infection model, this study examines the contribution of neutrophils to host defense to infection. Nontoxigenic El Tor O1V. choleraeinfection is characterized by the upregulation of interleukin-6 (IL-6), IL-10, and macrophage inflammatory protein 2 alpha in the intestine, indicating an acute innate immune response. Depletion of neutrophils from mice with anti-Ly6G IA8 monoclonal antibody led to decreased survival of mice. The role of neutrophils in protection of the host is to limit the infection to the intestine and control bacterial spread to extraintestinal organs. In the absence of neutrophils, the infection spread to the spleen and led to increased systemic levels of IL-1β and tumor necrosis factor alpha, suggesting the decreased survival in neutropenic mice is due to systemic shock. Neutrophils were found not to contribute to either clearance of colonizing bacteria or to alter the local immune response. However, when genes for secreted accessory toxins were deleted, the colonizing bacteria were cleared from the intestine, and this clearance is dependent upon neutrophils. Thus, the requirement for accessory toxins in virulence is negated in neutropenic mice, which is consistent with a role of accessory toxins in the evasion of innate immune cells in the intestine. Overall, these data support that neutrophils impact disease progression and suggest that neutrophil effectiveness can be manipulated through the deletion of accessory toxins.

scholarly journals The Sodium-Driven Flagellar Motor Controls Exopolysaccharide Expression in Vibrio cholerae

2004 ◽  
Vol 186 (15) ◽  
pp. 4864-4874 ◽  
Author(s):  
Crystal M. Lauriano ◽  
Chandradipa Ghosh ◽  
Nidia E. Correa ◽  
Karl E. Klose
Keyword(s):  
Vibrio Cholerae ◽  
Gene Transcription ◽  
Biofilm Formation ◽  
Diarrheal Disease ◽  
Response Regulator ◽  
Gene Clusters ◽  
Signaling Cascade ◽  
Genes Encoding ◽  
Life Threatening

ABSTRACT Vibrio cholerae causes the life-threatening diarrheal disease cholera. This organism persists in aquatic environments in areas of endemicity, and it is believed that the ability of the bacteria to form biofilms in the environment contributes to their persistence. Expression of an exopolysaccharide (EPS), encoded by two vps gene clusters, is essential for biofilm formation and causes a rugose colonial phenotype. We previously reported that the lack of a flagellum induces V. cholerae EPS expression. To uncover the signaling pathway that links the lack of a flagellum to EPS expression, we introduced into a rugose flaA strain second-site mutations that would cause reversion back to the smooth phenotype. Interestingly, mutation of the genes encoding the sodium-driven motor (mot) in a nonflagellated strain reduces EPS expression, biofilm formation, and vps gene transcription, as does the addition of phenamil, which specifically inhibits the sodium-driven motor. Mutation of vpsR, which encodes a response regulator, also reduces EPS expression, biofilm formation, and vps gene transcription in nonflagellated cells. Complementation of a vpsR strain with a constitutive vpsR allele likely to mimic the phosphorylated state (D59E) restores EPS expression and biofilm formation, while complementation with an allele predicted to remain unphosphorylated (D59A) does not. Our results demonstrate the involvement of the sodium-driven motor and suggest the involvement of phospho-VpsR in the signaling cascade that induces EPS expression. A nonflagellated strain expressing EPS is defective for intestinal colonization in the suckling mouse model of cholera and expresses reduced amounts of cholera toxin and toxin-coregulated pili in vitro. Wild-type levels of virulence factor expression and colonization could be restored by a second mutation within the vps gene cluster that eliminated EPS biosynthesis. These results demonstrate a complex relationship between the flagellum-dependent EPS signaling cascade and virulence.

scholarly journals 2,3-Butanediol Synthesis and the Emergence of the Vibrio cholerae El Tor Biotype

2006 ◽  
Vol 74 (12) ◽  
pp. 6547-6556 ◽  
Author(s):  
Sang Sun Yoon ◽  
John J. Mekalanos
Keyword(s):  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Sharp Decrease ◽  
Aquatic Environments ◽  
Environmental Niche ◽  
Medium Ph ◽  
Toxigenic Strains ◽  
El Tor ◽  
By Products ◽  
Evolutionary Fitness

ABSTRACT Vibrio cholerae is an aquatic bacterium that causes the severe diarrheal disease cholera. V. cholerae strains of the O1 serogroup exist as two biotypes, classical and El Tor. Toxigenic strains of the El Tor biotype emerged to cause the seventh pandemic of cholera in 1961 and subsequently displaced strains of the classical biotype both in the environment and as a cause of cholera within a decade. The factors that drove emergence of the El Tor biotype and the displacement of the classical biotype are unknown. Here, we show a unique difference in carbohydrate metabolism between these two biotypes. When grown with added carbohydrates, classical biotype strains generated a sharp decrease in medium pH, resulting in loss of viability. However, growth of El Tor biotype strain N16961 was enhanced due to its ability to produce 2,3-butanediol, a neutral fermentation end product, and suppress the accumulation of organic acids. An N16961 mutant (SSY01) defective in 2,3-butanediol synthesis showed the same defect in growth that classical biotype strains show in media rich in carbohydrates. Importantly, the SSY01 mutant was attenuated in its ability to colonize the intestines of infant mice, suggesting that host carbohydrates may be available to V. cholerae within the intestinal environment. Similarly, the SSY01 mutant failed to develop biofilms when utilizing N-acetyl-d-glucosamine as a carbon source. Because growth on N-acetyl-d-glucosamine likely reflects the ability of a strain to grow on chitin in certain aquatic environments, we conclude that the strains of classical biotype are likely defective compared to those of El Tor in growth in any environmental niche that is rich in chitin and/or other metabolizable carbohydrates. We propose that the ability to metabolize sugars without production of acid by-products might account for the improved evolutionary fitness of the V. cholerae El Tor biotype compared to that of the classical biotype both as a global cause of cholera and as an environmental organism.

scholarly journals Mr.Vc: a database of microarray and RNA-seq of Vibrio cholerae

Database ◽  
2019 ◽  
Vol 2019 ◽  
Author(s):  
Zhiyuan Zhang ◽  
Guozhong Chen ◽  
Jun Hu ◽  
Wajid Hussain ◽  
Fenxia Fan ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Gene Annotation ◽  
Relevant Information ◽  
Differentially Expressed ◽  
Data Repository ◽  
Rna Seq ◽  
Experimental Conditions ◽  
Life Threatening ◽  
Infectious Cycle

AbstractGram-negative bacterium Vibrio cholerae is the causative agent of cholera, a life-threatening diarrheal disease. During its infectious cycle, V. cholerae routinely switches niches between aquatic environment and host gastrointestinal tract, in which V. cholerae modulates its transcriptome pattern accordingly for better survival and proliferation. A comprehensive resource for V. cholerae transcriptome will be helpful for cholera research, including prevention, diagnosis and intervention strategies. In this study, we constructed a microarray and RNA-seq database of V. cholerae (Mr.Vc), containing gene transcriptional expression data of 145 experimental conditions of V. cholerae from various sources, covering 25 937 entries of differentially expressed genes. In addition, we collected relevant information including gene annotation, operons they may belong to and possible interaction partners of their protein products. With Mr.Vc, users can easily find transcriptome data they are interested in, such as the experimental conditions in which a gene of interest was differentially expressed in, or all genes that were differentially expressed in an experimental condition. We believe that Mr.Vc database is a comprehensive data repository dedicated to V. cholerae and could be a useful resource for all researchers in related fields. Mr.Vc is available for free at http://bioinfo.life.hust.edu.cn/mrvc.

scholarly journals Serotype has a significant impact on the virulence of 7th pandemic Vibrio cholerae O1

2020 ◽  
Author(s):  
Stefan L Nordqvist ◽  
Kaisa Thorell ◽  
Frida Nilsson ◽  
Madeleine Löfstrand ◽  
Arvid Hagelberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Virulence Genes ◽  
Diarrheal Disease ◽  
Selective Pressure ◽  
Infection Model ◽  
Infant Mouse ◽  
Mouse Infection Model ◽  
Vibrio Cholerae O1 ◽  
El Tor

AbstractOf over 200 different identified Vibrio cholerae serogroups only the O1 serogroup is consistently associated with endemic and epidemic cholera disease. The O1 serogroup has two serologically distinguishable variants, the Ogawa and Inaba serotypes, which differ only by a methyl group present on the terminal sugar of the Ogawa O-antigen but absent from Inaba strains. This methylation is catalyzed by a methyltransferase encoded by the wbeT gene, which in Inaba strains is disrupted by mutation. It is currently thought that there is little difference between the two serotypes. However, here we show, using isogenic pairs of O1 El Tor V. cholerae, that Inaba strains show significantly different patterns of gene expression and are significantly less able than the corresponding Ogawa strains to cause cholera in an infant mouse infection model. Our results suggest that changes in gene expression resulting from the loss of the wbeT gene lead to reduced virulence and possibly also reduced survival fitness outside the human host.Author SummaryThe bacterium Vibrio cholerae causes the pandemic diarrheal disease cholera. Despite many identified serotypes of V. cholerae only one, O1, causes pandemic cholera. The O1 serotype of pandemic V. cholerae has two distinguishable variants (called Ogawa and Inaba) long considered to be clinically and epidemiologically equivalent. Cholera outbreaks consist only of one the two variants at any time. In general, Ogawa strains cause the majority of outbreaks with relatively short-lived Inaba outbreaks occurring sporadically. We have suggested earlier that Inaba outbreaks occur during periods of environmental selective pressure against the Ogawa serotype. We demonstrate here that the two variants are not clinically equivalent. The Ogawa serotype is better able to respond to infection in an animal model by up regulating the expression of virulence genes essential for disease development. We suggest that this phenomenon is the result of wider ranging differences in gene expression resulting from the mutation that converts Ogawa into Inaba strains, and may help to explain the dominance of the Ogawa serotype in nature.

scholarly journals Host Intestinal Signal-Promoted Biofilm Dispersal Induces Vibrio cholerae Colonization

2014 ◽  
Vol 83 (1) ◽  
pp. 317-323 ◽  
Author(s):  
Amanda J. Hay ◽  
Jun Zhu
Keyword(s):  
Bile Salt ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Virulence Gene ◽  
Human Infection ◽  
Content Type ◽  
Abiotic Degradation ◽  
Contaminated Food ◽  
Free Media ◽  
Biofilm Matrix

Vibrio choleraecauses human infection through ingestion of contaminated food and water, leading to the devastating diarrheal disease cholera.V. choleraeforms matrix-encased aggregates, known as biofilms, in the native aquatic environment. While the formation ofV. choleraebiofilms has been well studied, little is known about the dispersal from biofilms, particularly upon entry into the host. In this study, we found that the exposure of mature biofilms to physiologic levels of the bile salt taurocholate, a host signal for the virulence gene induction ofV. cholerae, induces an increase in the number of detached cells with a concomitant decrease in biofilm mass. Scanning electron microscopy micrographs of biofilms exposed to taurocholate revealed an altered, perhaps degraded, appearance of the biofilm matrix. The inhibition of protein synthesis did not alter rates of detachment, suggesting thatV. choleraeundergoes a passive dispersal. Cell-free media from taurocholate-exposed biofilms contains a larger amount of free polysaccharide, suggesting an abiotic degradation of biofilm matrix by taurocholate. Furthermore, we found thatV. choleraeis only able to induce virulence in response to taurocholate after exit from the biofilm. Thus, we propose a model in whichV. choleraeingested as a biofilm has coopted the host-derived bile salt signal to detach from the biofilm and go on to activate virulence.

scholarly journals The Major Subunit of the Toxin-Coregulated Pilus TcpA Induces Mucosal and Systemic Immunoglobulin A Immune Responses in Patients with Cholera Caused by Vibrio cholerae O1 and O139

2004 ◽  
Vol 72 (8) ◽  
pp. 4448-4454 ◽  
Author(s):  
Muhammad Asaduzzaman ◽  
Edward T. Ryan ◽  
Manohar John ◽  
Long Hang ◽  
Ashraful I. Khan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Vibrio Cholerae ◽  
Surrogate Marker ◽  
Specific Response ◽  
Life Threatening Illness ◽  
Life Threatening ◽  
Toxin Coregulated Pilus ◽  
Mucosal Immune Responses ◽  
El Tor

ABSTRACT Diarrhea caused by Vibrio cholerae is known to give long-lasting protection against subsequent life-threatening illness. The serum vibriocidal antibody response has been well studied and has been shown to correlate with protection. However, this systemic antibody response may be a surrogate marker for mucosal immune responses to key colonization factors of this organism, such as the toxin-coregulated pilus (TCP) and other factors. Information regarding immune responses to TCP, particularly mucosal immune responses, is lacking, particularly for patients infected with the El Tor biotype of V. cholerae O1 or V. cholerae O139 since highly purified TcpA from these strains has not been available previously for use in immune assays. We studied the immune responses to El Tor TcpA in cholera patients in Bangladesh. Patients had substantial and significant increases in TcpA-specific antibody-secreting cells in the circulation on day 7 after the onset of illness, as well as similar mucosal responses as determined by an alternate technique, the assay for antibody in lymphocyte supernatant. Significant increases in antibodies to TcpA were also seen in sera and feces of patients on days 7 and 21 after the onset of infection. Overall, 93% of the patients showed a TcpA-specific response in at least one of the specimens compared with the results obtained on day 2 and with healthy controls. These results demonstrate that TcpA is immunogenic following natural V. cholerae infection and suggest that immune responses to this antigen should be evaluated for potential protection against subsequent life-threatening illness.

scholarly journals Role of Cholera Toxin in Vibrio cholerae Infection in Humans - A Review

2014 ◽  
Vol 22 ◽  
pp. 22-32 ◽  
Author(s):  
Partha Pal
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Indian Subcontinent ◽  
Bacterial Species ◽  
Human Pathogen ◽  
Watery Stool ◽  
The Past ◽  
Contaminated Food ◽  
El Tor

Vibrio cholerae, the causative agent of Asiatic cholera, is a gram-negative motile bacterial species acquired via oral ingestion of contaminated food or water sources. Cholera has spread from the Indian subcontinent where it is endemic to involve nearly the whole world seven times during the past 185 years. V. cholerae serogroup O1, biotype El Tor, has moved from Asia to cause pandemic disease in Africa and South America during the past 35 years. A new serogroup, O139, appeared in south Asia in 1992, has become endemic there, and threatens to start the next pandemic. The facultative human pathogen V. cholerae represents a paradigm that evolved from environmental non-pathogenic strains by acquisition of virulence genes. The major virulence factors of V. cholerae, cholera toxin (CTX) encoded by the ctxAB genes residing in the genome of filamentous lysogenic bacteriophage (CTXɸ) and toxin coregulated pilus (TCP) encoded by vibrio pathogenicity island (VPI). CTX, a potent stimulator of adenylate cyclase, causes the intestine to secrete watery fluid rich in sodium, bicarbonate, and potassium, in volumes far exceeding the intestinal absorptive capacity, by ADP-ribosylation of the alpha subunit of the GTP-binding protein. Thus intestinal infection with V. cholerae results in the loss of large volumes of watery stool, leading to severe and rapidly progressing dehydration and shock. Without adequate and appropriate rehydration therapy, severe cholera kills about half of affected individuals. Today, cholera still remains a burden mainly for underdeveloped countries, which cannot afford to establish or to maintain necessary hygienic and medical facilities. During the last three decades, intensive research has been undertaken to unravel the virulence properties and to study the epidemiology of this significant human pathogen. This review provides an overview of the role of CTX in the occurrence of this disease in humans.

scholarly journals Recent Vibrio cholerae O1 Epidemic Strains Are Unable To Replicate CTXΦ Prophage Genome

mSphere ◽  
2021 ◽  
Author(s):  
Kaoru Ochi ◽  
Tamaki Mizuno ◽  
Prosenjit Samanta ◽  
Asish K. Mukhopadhyay ◽  
Shin-ichi Miyoshi ◽  
...  
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Content Type ◽  
Ctxφ Prophage ◽  
Vibrio Cholerae O1 ◽  
El Tor

Cholera is an acute diarrheal disease caused by pathogenic strains of V. cholerae generated by lysogenization of the filamentous cholera toxin phage CTXΦ. The analysis revealed that recent isolates possessed altered CTXΦ prophage array of prototype El Tor strain and were defective in replicating the CTXΦ genome.

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