Roles of motility and flagellar structure in pathogenicity of Vibrio cholerae: analysis of motility mutants in three animal models

Abstract

Wild-type Vibrio cholerae of both El Tor and classical biotypes (strains N16961 and 395, respectively) and nonmotile mutant derivatives with and without flagellar structures were characterized in three different animal models: (i) the rabbit ileal loop, (ii) the removable intestinal tie adult rabbit diarrhea (RITARD) model, and (iii) the suckling mouse model. Both the wild-type strains and nonmotile mutants were toxinogenic in the rabbit ileal loop and the suckling mouse models. However, all of the nonmotile mutants produced significantly less fluid accumulation than did the wild-type parental strains. The two nonmotile mutants of strain N16961 did not adhere to rabbit ileal mucosa, but both nonmotile mutants derived from strain 395 exhibited adherence. In the RITARD model, the motile El Tor strains were more virulent than both the flagellate and aflagellate nonmotile mutants (all infected rabbits died within 18 h), while the nonmotile mutants, when fatalities occurred, required 78 to 105 h to produce a fatal outcome. Likewise, the motile classical parent 395 produced a fatal outcome within ca. 25 h, while nonmotile mutants required 69 to 96 h. The nonmotile flagellate strain KR31 was not significantly more virulent than the nonmotile aflagellate strain KR26. Of the two classical nonmotile mutants, KR1, which produces a coreless sheathlike structure, was clearly more virulent (5 of 10 rabbits died within 96 h), while KR3 (nonmotile, aflagellate) did not produce fatalities in any of the 10 rabbits tested. Similarly, no significant difference in diarrheagenicity or colonizing ability was detected between the two nonmotile mutants derived from the El Tor strain, but the classical nonmotile mutant with the coreless sheath caused significantly greater diarrhea and colonized for a longer time than did the isogenic nonmotile aflagellate strain, KR3. No significant differences between the nonmotile mutants were detected in competition studies done with suckling mice. Analysis of the wild-type and mutant strains in these three animal models clearly demonstrated a role for motility in V. cholerae pathogenicity, while analysis of only the nonmotile mutants derived from the classical parent suggested a role for flagellar structures.

Directed delivery of heat-labile enterotoxin by enterotoxigenic Escherichia coli

“…Another aspect of toxin delivery studied here, flagellar locomotion, has been shown to be essential for virulence in a diverse group of pathogens (Giron et al, 2002;Dons et al, 2004;Stecher et al, 2004) including V. cholerae (Richardson, 1991;Gardel and Mekalanos, 1996). Our data suggest that flagellar-based motility is required for efficient delivery of LT.…”

Roles for motility in bacterial–host interactions

“…The presence of this organism in aquatic environments contributes to endemic disease, and the evolution of new pathogenic strains provides the potential for epidemic, and even pandemic, spread (Mel and Mekalanos, 1996). The relationship between V. cholerae motility and pathogenesis has been studied for many years (Fretter et al, 1981); however, a well-defined role for motility in this context still remains uncertain (Richardson, 1991;Gardel and Mekalanos, 1996). Some interesting links between the expression of virulence determinants and motility have been found recently.…”

Use of recombinase gene fusions to identify Vibrio cholerae genes induced during infection

“…Three of the in vivo-induced transcription units identified in this study relate to bacterial motility and chemotaxis. There is evidence that suggests that motility and chemotaxis are required for full virulence of V. cholerae in various adult animal models of cholera Richardson, 1991). In contrast, in the infant mouse model of cholera, chemotactic motility is actually a detriment in that non-chemotactic mutant strains survive in greater numbers than wild-type vibrios and produce a more rapid and severe disease .…”