scholarly journals Prolonged Colonization of Mice by Vibrio cholerae El Tor O1 Depends on Accessory Toxins

2007 ◽  
Vol 75 (10) ◽  
pp. 5043-5051 ◽  
Author(s):  
Verena Olivier ◽  
Nita H. Salzman ◽  
Karla J. Fullner Satchell

ABSTRACT Cholera epidemics caused by Vibrio cholerae El Tor O1 strains are typified by a large number of asymptomatic carriers who excrete vibrios but do not develop diarrhea. This carriage state was important for the spread of the seventh cholera pandemic as the bacterium was mobilized geographically, allowing the global dispersion of this less virulent strain. Virulence factors associated with the development of the carriage state have not been previously identified. We have developed an animal model of cholera in adult C57BL/6 mice wherein V. cholerae colonizes the mucus layer and forms microcolonies in the crypts of the distal small bowel. Colonization occurred 1 to 3 h after oral inoculation and peaked at 10 to 12 h, when bacterial loads exceeded the inoculum by 10- to 200-fold, indicating bacterial growth within the small intestine. After a clearance phase, the number of bacteria within the small intestine, but not those in the cecum or colon, stabilized and persisted for at least 72 h. The ability of V. cholerae to prevent clearance and establish this prolonged colonization was associated with the accessory toxins hemolysin, the multifunctional autoprocessing RTX toxin, and hemagglutinin/protease and did not require cholera toxin or toxin-coregulated pili. The defect in colonization attributed to the loss of the accessory toxins may be extracellularly complemented by inoculation of the defective strain with an isogenic colonization-proficient V. cholerae strain. This work thus demonstrates that secreted accessory toxins modify the host environment to enable prolonged colonization of the small intestine in the absence of overt disease symptoms and thereby contribute to disease dissemination via asymptomatic carriers.

2019 ◽  
Author(s):  
Nguyen T. Q. Nhu ◽  
Helen J. Wang ◽  
Yann S. Dufour

AbstractIntestinal mucus is the first line of defense against intestinal pathogens. It acts as a physical barrier between the epithelial tissues and luminal microbes. Enteropathogens, such as Vibrio cholerae, must compromise or circumvent the mucus barrier to establish a successful infection. We investigated how motile V. cholerae is able to penetrate mucus using single cell tracking in unprocessed porcine intestinal mucus. We found that changes in pH within the range of what has been measured in the human small intestine indirectly affect V. cholerae flagellar motor torque, and consequently, mucus penetration. Microrheological measurements indicate that the viscoelasticity of mucus does not change substantially within the physiological pH range and that commercially available mucins do not form gels when rehydrated. Finally, we found that besides the reduction in motor torque, El Tor and Classical biotypes have different responses to acidic pH. For El Tor, acidic pH promotes surface attachment that is mediated by activation of the mannose-sensitive haemagglutinin (MshA) pilus without a measurable change in the total cellular concentration of the secondary messenger cyclic dimeric guanosine monophosphate (c-di-GMP). Overall, our results support that the high torque of V. cholerae flagellar motor is critical for mucus penetration and that the pH gradient in the small intestine is likely an important factor in determining the preferred site of infection.Author summaryThe diarrheal disease cholera is still a burden for populations in developing countries with poor sanitation. To develop effective vaccines and prevention strategies against Vibrio cholerae, we must understand the initial steps of infection leading to the colonization of the small intestine. To infect the host and deliver the cholera toxin, V. cholerae has to penetrate the mucus layer protecting the intestinal tissues. However, V. cholerae’s interactions with intestinal mucus has not been extensively investigated. In this report, we demonstrate using single cell tracking that V. cholerae is able to penetrate native intestinal mucus using flagellar motility. In addition, we found that a strong motor torque is required for mucus penetration and, that torque is weakened in acidic environments even though the motor is powered by a sodium potential. This finding has important implications for understanding the dynamics of infection because pH varies significantly along the small intestine, between individuals, and between species. Blocking mucus penetration by interfering with V. cholerae’s flagellar motility, reinforcing the mucosa, controlling intestinal pH, or manipulating the intestinal microbiome, will offer new strategies to fight cholera.


2021 ◽  
Author(s):  
Nguyen T. Q. Nhu ◽  
John S. Lee ◽  
Helen J. Wang ◽  
Yann S. Dufour

Intestinal mucus is the first line of defense against intestinal pathogens. It acts as a physical barrier between epithelial tissues and the lumen that enteropathogens must overcome to establish a successful infection. We investigated the motile behavior of two V. cholerae strains (El Tor C6706 and Classical O395) in mucus using single cell tracking in unprocessed porcine intestinal mucus. We determined that V. cholerae is able to penetrate mucus using flagellar motility and that alkaline pH increases swimming speed, and consequently, improves mucus penetration. Microrheological measurements indicate that changes in pH between 6 and 8 (the physiological range for the human small intestine) had little effect on the viscoelastic properties of mucus. Finally, we determined that acidic pH promotes surface attachment by activating the mannose-sensitive haemagglutinin (MshA) pilus in V. cholerae El Tor C6706 without a measurable change in the total cellular concentration of the secondary messenger cyclic dimeric guanosine monophosphate (c-di-GMP). Overall, our results support that pH is an important factor affecting the motile behavior of V. cholerae and its ability to penetrate mucus. Therefore, changes in pH along the human small intestine may play a role in determining the preferred site for V. cholerae during infection. IMPORTANCE The diarrheal disease cholera is still a burden for populations in developing countries with poor sanitation. To develop effective vaccines and prevention strategies against Vibrio cholerae, we must understand the initial steps of infection leading to the colonization of the small intestine. To infect the host and deliver the cholera toxin, V. cholerae has to penetrate the mucus layer protecting the intestinal tissues. However, the interaction of V. cholerae with intestinal mucus has not been extensively investigated. In this report, we demonstrated using single cell tracking that V. cholerae is able to penetrate intestinal mucus using flagellar motility. In addition, we observed that alkaline pH improves the ability of V. cholerae to penetrate mucus. This finding has important implications for understanding the dynamics of infection because pH varies significantly along the small intestine, between individuals, and between species. Blocking mucus penetration by interfering with flagellar motility in V. cholerae, reinforcing the mucosa, controlling intestinal pH, or manipulating the intestinal microbiome, will offer new strategies to fight cholera.


2005 ◽  
Vol 134 (3) ◽  
pp. 645-648 ◽  
Author(s):  
M. S. ISLAM ◽  
M. M. GOLDAR ◽  
M. G. MORSHED ◽  
H. B. M. BAKHT ◽  
M. S. ISLAM ◽  
...  

The chemotactic response of Vibrio cholerae O1 towards the mucilaginous sheath of Anabaena sp. was investigated by capillary tube method using a virulent strain of V. cholerae O1, El Tor, Ogawa (3083-T) and its isogenic mutant (HAP-1-T) that lacks the hap gene, which codes for mucinase (HA/protease). Homogenates of Anabaena sp. and purified mucin were used in this study as chemoattractants. Results showed 5·7% bacterial accumulation of wild-type V. cholerae O1 towards 4% homogenates of Anabaena sp. whereas, its mutant (hap−) showed 2·9% accumulation after 90 min. The higher percentage of attraction of wild-type V. cholerae O1 than the mutant (hap−) towards mucin and the homogenates of Anabaena sp. might be due to the activity of mucinase. These results indicate the role of mucinase in the chemotactic motility of V. cholerae O1 towards Anabaena sp.


2020 ◽  
Vol 56 (9) ◽  
pp. 1055-1069
Author(s):  
N. I. Smirnova ◽  
A. A. Kritsky ◽  
J. V. Alkhova ◽  
E. Yu. Agafonova ◽  
E. Yu. Shchelkanova ◽  
...  

The Lancet ◽  
1979 ◽  
Vol 314 (8134) ◽  
pp. 147-148 ◽  
Author(s):  
K.J. Towner ◽  
N.J. Pearson ◽  
F. O'Grady
Keyword(s):  

2015 ◽  
Vol 205 (2) ◽  
pp. 195-200 ◽  
Author(s):  
Debdutta Bhattacharya ◽  
Shuchismita Dey ◽  
Gururaja Perumal Pazhani ◽  
Thandavarayan Ramamurthy ◽  
Mahantesh V. Parande ◽  
...  

2006 ◽  
Vol 55 (11) ◽  
pp. 1559-1562 ◽  
Author(s):  
G. Balakrish Nair ◽  
Ashrafus Safa ◽  
N. A. Bhuiyan ◽  
Suraia Nusrin ◽  
Denise Murphy ◽  
...  

2012 ◽  
Vol 17 (5) ◽  
pp. 31-35
Author(s):  
V. N. Savelyev ◽  
I. V. Savelyeva ◽  
B. V. Babenyshev ◽  
A. N. Kulichenko

In a comparative perspective studied cholera outbreak in the Caucasus due to typical toxigenic and genetically modified (hybrid) El Tor variant strains have been studied. Revealed features of the genetic structure of the genome, factors and ways of transmission of the causative agent of modern cholera El tor should be considered when improving the program of epidemiological supervision in terms of enhancing antiepidemic and prevention measures in cholera, the causative factor of which are of hybrid variants of Vibrio cholerae El tor.


2003 ◽  
Vol 71 (2) ◽  
pp. 1020-1025 ◽  
Author(s):  
Shah M. Faruque ◽  
M. Kamruzzaman ◽  
Ismail M. Meraj ◽  
Nityananda Chowdhury ◽  
G. Balakrish Nair ◽  
...  

ABSTRACT The major virulence factors of toxigenic Vibrio cholerae are cholera toxin (CT), which is encoded by a lysogenic bacteriophage (CTXΦ), and toxin-coregulated pilus (TCP), an essential colonization factor which is also the receptor for CTXΦ. The genes for the biosynthesis of TCP are part of a larger genetic element known as the TCP pathogenicity island. To assess their pathogenic potential, we analyzed environmental strains of V. cholerae carrying genetic variants of the TCP pathogenicity island for colonization of infant mice, susceptibility to CTXΦ, and diarrheagenicity in adult rabbits. Analysis of 14 environmental strains, including 3 strains carrying a new allele of the tcpA gene, 9 strains carrying a new allele of the toxT gene, and 2 strains carrying conventional tcpA and toxT genes, showed that all strains colonized infant mice with various efficiencies in competition with a control El Tor biotype strain of V. cholerae O1. Five of the 14 strains were susceptible to CTXΦ, and these transductants produced CT and caused diarrhea in adult rabbits. These results suggested that the new alleles of the tcpA and toxT genes found in environmental strains of V. cholerae encode biologically active gene products. Detection of functional homologs of the TCP island genes in environmental strains may have implications for understanding the origin and evolution of virulence genes of V. cholerae.


1998 ◽  
Vol 14 (3) ◽  
pp. 465-471 ◽  
Author(s):  
Waldêny Colaço ◽  
Sandoval Vieira da Silva Filho ◽  
Dália dos Prazeres Rodrigues ◽  
Ernesto Hofer

No período de 1992 a 1994, foram analisadas 2.585 amostras de águas de diferentes ecossistemas, acrescidas de 91 espécimens de alimentos visando ao monitoramento de Vibrio cholerae O1 no Estado de Pernambuco. Nas 2.676 amostras foram detectadas 193 cepas de Vibrio cholerae O1 (7,21%) com predominância do sorovar Inaba (183-94,8%) sobre Ogawa (10-5,1%), todas classificadas no biotipo El Tor e sensíveis à tetraciclina. Numa parcela de setenta amostras selecionadas ao acaso, mas incluindo todas do sorovar Ogawa, foi evidenciada a produção de toxina colérica. A maior incidência do vibrião colérico em águas de rios, canais e de esgoto, representando 86% dos isolados, indicou a contaminação fecal por excretores como a causa preponderante na disseminação da bactéria nos sistemas aquáticos. Assinala-se a discreta ocorrrência de V. cholerae O1 nos alimentos processados (2,1%).


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