Complex symbiont-pathogen interactions inhibit intestinal repair

Fast, David E.; Petkau, Kristina; Ferguson, Meghan; Shin, Min Jeong; Galenza, Anthony; Kostiuk, Benjamin; Pukatzki, Stefan; Foley, Edan

doi:10.1101/746305

Cited by 3 publications

(3 citation statements)

References 74 publications

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“…More recently, we showed that the T6SS also affects epithelial renewal in infected flies. In agreement with previous work (139), we showed that V. cholerae causes extensive damage to the midgut epithelium, but fails to activate compensatory proliferation in basal progenitor cells (166). Removal of the T6SS diminishes epithelial damage, and restores renewal in infected midguts.…”

Section: Vibrio Cholerae and Isc Growthsupporting

confidence: 93%

Host-Microbe-Pathogen Interactions: A Review of Vibrio cholerae Pathogenesis in Drosophila

Davoodi

Foley

2020

Front. Immunol.

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Most animals maintain mutually beneficial symbiotic relationships with their intestinal microbiota. Resident microbes in the gastrointestinal tract breakdown indigestible food, provide essential nutrients, and, act as a barrier against invading microbes, such as the enteric pathogen Vibrio cholerae. Over the last decades, our knowledge of V. cholerae pathogenesis, colonization, and transmission has increased tremendously. A number of animal models have been used to study how V. cholerae interacts with host-derived resources to support gastrointestinal colonization. Here, we review studies on host-microbe interactions and how infection with V. cholerae disrupts these interactions, with a focus on contributions from the Drosophila melanogaster model. We will discuss studies that highlight the connections between symbiont, host, and V. cholerae metabolism; crosstalk between V. cholerae and host microbes; and the impact of the host immune system on the lethality of V. cholerae infection. These studies suggest that V. cholerae modulates host immune-metabolic responses in the fly and improves Vibrio fitness through competition with intestinal microbes.

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Section: Vibrio Cholerae and Isc Growthsupporting

confidence: 93%

Host-Microbe-Pathogen Interactions: A Review of Vibrio cholerae Pathogenesis in Drosophila

Davoodi

Foley

2020

Front. Immunol.

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“…Of note, similar to our study, flagellar genes were identified as important colonization determinants of one microbiome member Acetobacter fabarum (47), suggesting this may be a common feature for bacterial persistence in the fly gut. Our previous work and other reports have highlighted a role for the microbiota in modulating enteric infection by bacteria, yeast, and viruses (48)(49)(50)(51)(52). We observed that colonization with a single member of the microbiota, Lactiplantibacillus plantarum, is sufficient to reduce mortality associated with S. marcescens, P. aeruginosa (41) and P. entomophila (51).…”

Section: Discussionsupporting

confidence: 50%

Massively parallel mutant selection identifies genetic determinants ofPseudomonas aeruginosacolonization ofDrosophila melanogaster

Miles,

Lozano,

Rajendhran

et al. 2023

Preprint

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Pseudomonas aeruginosais recognized for its ability to colonize diverse habitats and cause disease in a variety of hosts, including plants, invertebrates, and mammals. Understanding how this bacterium is able to occupy wide-ranging niches is important for deciphering its ecology. We used transposon sequencing (Tn-Seq, also known as INSeq) to identify genes inP. aeruginosathat contribute to fitness during colonization ofDrosophila melanogaster. Our results reveal a suite of critical factors, including those that contribute to polysaccharide production, DNA repair, metabolism, and respiration. Comparison of candidate genes with fitness determinants discovered in previous studies ofP. aeruginosaidentified several genes required for colonization and virulence determinants that are conserved across hosts and tissues. This analysis provides evidence for both the conservation of function of several genes across systems, as well as host-specific functions. These findings, which represent the first use of transposon sequencing of a gut pathogen inDrosophila, demonstrate the power of Tn-Seq in the fly model system and advance existing knowledge of intestinal pathogenesis byD. melanogaster,revealing bacterial colonization determinants that contribute to a comprehensive portrait ofP.aeruginosalifestyles across habitats.ImportanceDrosophila melanogasteris a powerful model for understanding host-pathogen interactions. Research with this system has yielded notable insights into mechanisms of host immunity and defense, many of which emerged from analysis of bacterial mutants defective for well-characterized virulence factors. These foundational studies – and advances in high-throughput sequencing of transposon mutants – support unbiased screens of bacterial mutants in the fly. To investigate mechanisms of host-pathogen interplay and exploit the tractability of this model host, we used a high-throughput, genome-wide mutant analysis to find genes that enable a pathogen,P. aeruginosa, to colonize the fly. Our analysis reveals critical mediators ofP. aeruginosaestablishment in its host, some of which are required across fly and mouse systems. These findings demonstrate the utility of massively parallel mutant analysis and provide a platform for aligning the fly toolkit with comprehensive bacterial genomics.

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“…The bacterial dynamics can be complex. In the Drosophila model, V. cholerae with a functional T6SS inhibited host intestinal repair only when three common fly commensals were present altogether, rather than individually (Fast et al, 2020). In infant mice, V. cholerae expressing T6SS were able to compete against commensal Escherichia coli, with the E. coli demonstrating a 300-fold drop in CFU count per small intestine homogenate when compared to the group infected with V. cholerae expressing a defective T6SS (Zhao et al, 2018).…”

Section: Vibrio Cholerae Resistance To Gut Microbiome Dynamicsmentioning

confidence: 99%

Advances in cholera research: from molecular biology to public health initiatives

et al. 2023

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The aquatic bacterium Vibrio cholerae is the etiological agent of the diarrheal disease cholera, which has plagued the world for centuries. This pathogen has been the subject of studies in a vast array of fields, from molecular biology to animal models for virulence activity to epidemiological disease transmission modeling. V. cholerae genetics and the activity of virulence genes determine the pathogenic potential of different strains, as well as provide a model for genomic evolution in the natural environment. While animal models for V. cholerae infection have been used for decades, recent advances in this area provide a well-rounded picture of nearly all aspects of V. cholerae interaction with both mammalian and non-mammalian hosts, encompassing colonization dynamics, pathogenesis, immunological responses, and transmission to naïve populations. Microbiome studies have become increasingly common as access and affordability of sequencing has improved, and these studies have revealed key factors in V. cholerae communication and competition with members of the gut microbiota. Despite a wealth of knowledge surrounding V. cholerae, the pathogen remains endemic in numerous countries and causes sporadic outbreaks elsewhere. Public health initiatives aim to prevent cholera outbreaks and provide prompt, effective relief in cases where prevention is not feasible. In this review, we describe recent advancements in cholera research in these areas to provide a more complete illustration of V. cholerae evolution as a microbe and significant global health threat, as well as how researchers are working to improve understanding and minimize impact of this pathogen on vulnerable populations.

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Complex symbiont-pathogen interactions inhibit intestinal repair

Cited by 3 publications

References 74 publications

Host-Microbe-Pathogen Interactions: A Review of Vibrio cholerae Pathogenesis in Drosophila

Host-Microbe-Pathogen Interactions: A Review of Vibrio cholerae Pathogenesis in Drosophila

Massively parallel mutant selection identifies genetic determinants ofPseudomonas aeruginosacolonization ofDrosophila melanogaster

Advances in cholera research: from molecular biology to public health initiatives

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