The Native Microbial Community of Gastropod-Associated Phasmarhabditis Species Across Central and Southern California.

Nematodes in the genus Phasmarhabditis can infect and kill slugs and snails, which are important agricultural pests. This useful trait has been commercialized by the corporation BASF after they mass produced a product labeled Nemaslug®. The product contains Phasmarhabditis hermaphrodita, which has been cultured with Moraxella osloensis, a bacterial strain that was originally thought to be responsible for causing mortality in slugs and snails. The exact mechanism leading to death in a Phasmarhabditis infected host is unknown but may involve contributions from nematode-associated bacteria. The naturally occurring microbial community of Phasmarhabditis is unexplored; the previous Phasmarhabditis microbial community studies have focused on laboratory grown or commercially reared nematodes, and in order to obtain a deeper understanding of the parasite and its host interactions, it is crucial to characterize the natural microbial communities associated with this organism in the wild. We sampled Phasmarhabditis californica, Phasmarhabditis hermaphrodita, and Phasmarhabditis papillosa directly from their habitats in Central and Southern California nurseries and garden centers and identified their native microbial community via 16S amplicon sequencing. We found that the Phasmarhabditis microbial community was influenced by species, location, and possibly gastropod host from which the nematode was collected. The predominant bacteria of the Phasmarhabditis isolates collected included Shewanella, Clostridium perfringens, Aeromonadaceae, Pseudomonadaceae, and Acinetobacter. Phasmarhabditis papillosa isolates exhibited an enrichment with species belonging to Acinetobacter or Pseudomonadaceae. However, further research must be performed to determine if this is due to the location of isolate collection or a species specific microbial community pattern. More work on the natural microbial community of Phasmarhabditis is needed to determine the role of bacteria in nematode virulence.

A commensal-encoded genotoxin drives restriction of Vibrio cholerae colonization and host gut microbiome remodeling.

SignificanceIn a polymicrobial battlefield where different species compete for nutrients and colonization niches, antimicrobial compounds are the sword and shield of commensal microbes in competition with invading pathogens and each other. The identification of an Escherichia coli-produced genotoxin, colibactin, and its specific targeted killing of enteric pathogens and commensals, including Vibrio cholerae and Bacteroides fragilis, sheds light on our understanding of intermicrobial interactions in the mammalian gut. Our findings elucidate the mechanisms through which genotoxins shape microbial communities and provide a platform for probing the larger role of enteric multibacterial interactions regarding infection and disease outcomes.

A dysbiotic gut microbiome suppresses antibody mediated-protection against Vibrio cholerae.

Cholera is a severe diarrheal disease that places a significant burden on global health. Cholera's high morbidity demands effective prophylactic strategies, but oral cholera vaccines exhibit variable efficacy in human populations. One contributor of variance in human populations is the gut microbiome, which in cholera-endemic areas is modulated by malnutrition, cholera, and non-cholera diarrhea. We conducted fecal transplants from healthy human donors and model communities of either human gut microbes that resemble healthy individuals or those of individuals recovering from diarrhea in various mouse models. We show microbiome-specific effects on host antibody responses against Vibrio cholerae, and that dysbiotic human gut microbiomes representative of cholera-endemic areas suppress the immune response against V. cholerae via CD4+ lymphocytes. Our findings suggest that gut microbiome composition at time of infection or vaccination may be pivotal for providing robust mucosal immunity, and suggest a target for improved prophylactic and therapeutic strategies for cholera.

Protocol for Microbiome Transplantation in Suckling Mice during Vibrio cholerae Infection to Study Commensal-Pathogen Interactions.

The gut microbiome plays an important role in the exclusion of pathogens and, thus, infection outcomes. Microbiome-pathogen interaction studies are complicated by a lack of tractable animal models and differences in animal model versus human microbiomes. We have adapted the suckling mouse model of infection of the human pathogen Vibrio cholerae to clear murine microbes and establish human-associated gut microbes during infection. Our method allows for the easy examination of the contribution of different human microbial communities to enteropathogenesis. For complete details on the use and execution of this protocol, please refer to Alavi et al. (2020).

Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection.

The gut microbiome is the resident microbial community of the gastrointestinal tract. This community is highly diverse, but how microbial diversity confers resistance or susceptibility to intestinal pathogens is poorly understood. Using transplantation of human microbiomes into several animal models of infection, we show that key microbiome species shape the chemical environment of the gut through the activity of the enzyme bile salt hydrolase. The activity of this enzyme reduced colonization by the major human diarrheal pathogen Vibrio cholerae by degrading the bile salt taurocholate that activates the expression of virulence genes. The absence of these functions and species permits increased infection loads on a personal microbiome-specific basis. These findings suggest new targets for individualized preventative strategies of V. cholerae infection through modulating the structure and function of the gut microbiome.