Adaptation to an amoeba host drives selection of virulence-associated traits in Vibrio cholerae

Abstract

Predation by heterotrophic protists drives the emergence of adaptive traits in bacteria, and often these traits lead to altered interactions with hosts and persistence in the environment. Here we studied adaptation of the cholera pathogen, Vibrio cholerae during long-term co-incubation with the protist host, Acanthamoeba castellanii. We determined phenotypic and genotypic changes associated with long-term intra-amoebal host adaptation and how this impacts pathogen survival and fitness. We showed that adaptation to the amoeba host leads to temporal changes in multiple phenotypic traits in V. cholerae that facilitate increased survival and competitive fitness in amoeba. Genome sequencing and mutational analysis revealed that these altered lifestyles were linked to non-synonymous mutations in conserved regions of the flagellar transcriptional regulator, flrA. Additionally, the mutations resulted in enhanced colonisation in zebrafish, establishing a link between adaptation of V. cholerae to amoeba predation and enhanced environmental persistence. Our results show that pressure imposed by amoeba on V. cholerae selects for flrA mutations that serves as a key driver for adaptation. Importantly, this study provides evidence that adaptive traits that evolve in pathogens in response to environmental predatory pressure impact the colonisation of eukaryotic organisms by these pathogens.

Phagotrophic Protists Modulate Copper Resistance of the Bacterial Community in Soil

“…These evolved defense mechanisms can function as virulence factors that are necessary for bacterial survival in macrophages and persistence in the environment . Thus, adaptation to protist hosts is widely recognized as training grounds for bacterial pathogenicity and the emergence of human pathogens from environmental reservoirs. , Among defense mechanisms, bacterial Cu resistance is an essential virulence determinant for bacterial pathogenicity, enabling bacteria to detoxify Cu toxicity during infection and survive in mammalian hosts . Some studies also demonstrated that Cu resistance facilitates tissue colonization, infection, and inflammation for a variety of bacterial pathogens, such as E.…”

“…74 Thus, adaptation to protist hosts is widely recognized as training grounds for bacterial pathogenicity and the emergence of human pathogens from environmental reservoirs. 75,76 Among defense mechanisms, bacterial Cu resistance is an essential virulence determinant for bacterial pathogenicity, enabling bacteria to detoxify Cu toxicity during infection and survive in mammalian hosts. 14 Some studies also demonstrated that Cu resistance facilitates tissue colonization, infection, and inflammation for a variety of bacterial pathogens, such as E. coli, Mycobacterium tuberculosis, Acinetobacter baumannii, Listeria monocytogenes, P. aeruginosa, and Staphylococcus aureus.…”

Isolation and Genome Analysis of an Amoeba-Associated Bacterium Dyella terrae Strain Ely Copper Mine From Acid Rock Drainage in Vermont, United States

“…These are secretion P-type DNA transfer genes that aid in substrate secretion through a cell envelope spanning structure, preventing bacterial cell lysis and encouraging cell growth ( Christie, 2004 ). Dyella terrae strain Ely Copper Mine may have evolved these mechanisms as an adaptive response to predation pressure, enhancing its persistence ( Hoque et al, 2021 ). Other virulence genes were also found in the genome, including those encoding an ANK-containing protein, which has unclear origins but may be acquired from eukaryotes via horizontal gene transfer or result from convergent evolution ( Al-Khodor et al, 2010 ).…”

Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae

“…A previous study showed that nonsynonymous SNP (nsSNP) mutations in conserved regions of FlrA were detected duringc long-term coincubation with Acanthamoeba castellanii (A. castellanii), and during long-term intra-amoebal host adaptation of V. cholerae resulted in enhanced colonization in zebrafish [45]. All of the nsSNP of FlrA occurred in the central domain and one deletion occurred in the flanking region of the central domain and C-terminal HTH domain.…”