RESUMEN
While the major virulence factors for Vibrio cholerae, the cause of the devastating diarrheal disease cholera, have been extensively studied, the initial intestinal colonization of the bacterium is not well understood because non-human adult animals are refractory to its colonization. Recent studies suggest the involvement of an interbacterial killing device known as the type VI secretion system (T6SS). Here, we tested the T6SS-dependent interaction of V. cholerae with a selection of human gut commensal isolates. We show that the pathogen efficiently depleted representative genera of the Proteobacteria in vitro, while members of the Enterobacter cloacae complex and several Klebsiella species remained unaffected. We demonstrate that this resistance against T6SS assaults was mediated by the production of superior T6SS machinery or a barrier exerted by group I capsules. Collectively, our data provide new insights into immunity protein-independent T6SS resistance employed by the human microbiota and colonization resistance in general.
Asunto(s)
Cólera/microbiología , Enterobacter cloacae/inmunología , Microbioma Gastrointestinal/inmunología , Klebsiella/inmunología , Sistemas de Secreción Tipo VI/metabolismo , Cápsulas Bacterianas/inmunología , Cápsulas Bacterianas/metabolismo , Cólera/inmunología , Resistencia a la Enfermedad/inmunología , Enterobacter cloacae/metabolismo , Humanos , Klebsiella/metabolismo , Vibrio cholerae/inmunología , Vibrio cholerae/patogenicidad , Factores de Virulencia/inmunología , Factores de Virulencia/metabolismoRESUMEN
Mobile genetic elements (MGEs) drive genetic transfers between bacteria using mechanisms that require a physical interaction with the cellular envelope. In the high-priority multidrug-resistant nosocomial pathogens (ESKAPE), the first point of contact between the cell and virions or conjugative pili is the capsule. While the capsule can be a barrier to MGEs, it also evolves rapidly by horizontal gene transfer (HGT). Here, we aim at understanding this apparent contradiction by studying the covariation between the repertoire of capsule genes and MGEs in approximately 4,000 genomes of Klebsiella pneumoniae (Kpn). We show that capsules drive phage-mediated gene flow between closely related serotypes. Such serotype-specific phage predation also explains the frequent inactivation of capsule genes, observed in more than 3% of the genomes. Inactivation is strongly epistatic, recapitulating the capsule biosynthetic pathway. We show that conjugative plasmids are acquired at higher rates in natural isolates lacking a functional capsular locus and confirmed experimentally this result in capsule mutants. This suggests that capsule inactivation by phage pressure facilitates its subsequent reacquisition by conjugation. Accordingly, capsule reacquisition leaves long recombination tracts around the capsular locus. The loss and regain process rewires gene flow toward other lineages whenever it leads to serotype swaps. Such changes happen preferentially between chemically related serotypes, hinting that the fitness of serotype-swapped strains depends on the host genetic background. These results enlighten the bases of trade-offs between the evolution of virulence and multidrug resistance and caution that some alternatives to antibiotics by selecting for capsule inactivation may facilitate the acquisition of antibiotic resistance genes (ARGs).
Asunto(s)
Cápsulas Bacterianas/metabolismo , Secuencias Repetitivas Esparcidas , Klebsiella pneumoniae/metabolismo , Vías Biosintéticas , Conjugación Genética , Flujo Génico , Genoma Bacteriano , Klebsiella pneumoniae/genética , Recombinación GenéticaRESUMEN
The fitness cost associated with the production of bacterial capsules is considered to be offset by the protection provided by these extracellular structures against biotic aggressions or abiotic stress. However, it is unknown if the capsule contributes to fitness in the absence of these. Here, we explored conditions favouring the maintenance of the capsule in Klebsiella pneumoniae, where the capsule is known to be a major virulence factor. Using short-term experimental evolution on different Klebsiella strains, we showed that small environmental variations have a strong impact on the maintenance of the capsule. Capsule inactivation is frequent in nutrient-rich, but scarce in nutrient-poor media. Competitions between wild-type and capsule mutants in nine different strains confirmed that the capsule is costly in nutrient-rich media. Surprisingly, these results also showed that the presence of a capsule provides a clear fitness advantage in nutrient-poor conditions by increasing both growth rates and population yields. The comparative analyses of the wild-type and capsule mutants reveal complex interactions between the environment, genetic background and serotype even in relation to traits known to be relevant during pathogenesis. In conclusion, our data suggest there are novel roles for bacterial capsules yet to be discovered and further supports the notion that the capsule's role in virulence may be a by-product of its contribution to bacterial adaptation outside the host.
Asunto(s)
Cápsulas Bacterianas , Klebsiella , Klebsiella pneumoniae/genética , Nutrientes , VirulenciaRESUMEN
Klebsiella species are able to colonize a wide range of environments and include worrisome nosocomial pathogens. Here, we sought to determine the abundance and infectivity of prophages of Klebsiella to understand how the interactions between induced prophages and bacteria affect population dynamics and evolution. We identified many prophages in the species, placing these taxa among the top 5% of the most polylysogenic bacteria. We selected 35 representative strains of the Klebsiella pneumoniae species complex to establish a network of induced phage-bacteria interactions. This revealed that many prophages are able to enter the lytic cycle, and subsequently kill or lysogenize closely related Klebsiella strains. Although 60% of the tested strains could produce phages that infect at least one other strain, the interaction network of all pairwise cross-infections is very sparse and mostly organized in modules corresponding to the strains' capsule serotypes. Accordingly, capsule mutants remain uninfected showing that the capsule is a key factor for successful infections. Surprisingly, experiments in which bacteria are predated by their own prophages result in accelerated loss of the capsule. Our results show that phage infectiousness defines interaction modules between small subsets of phages and bacteria in function of capsule serotype. This limits the role of prophages as competitive weapons because they can infect very few strains of the species complex. This should also restrict phage-driven gene flow across the species. Finally, the accelerated loss of the capsule in bacteria being predated by their own phages, suggests that phages drive serotype switch in nature.