Ambient pH Alters the Protein Content of Outer Membrane Vesicles, Driving Host Development in a Beneficial Symbiosis

• Published in: Journal of bacteriology 2019-10, Vol.201 (20), p.1
• Main Authors: Lynch, Jonathan B, Schwartzman, Julia A, Bennett, Brittany D, McAnulty, Sarah J, Knop, Mirjam, Nyholm, Spencer V, Ruby, Edward G
• Format: Article
• Language: English
• Subjects: Aliivibrio fischeri - metabolism; Aliivibrio fischeri - physiology; Animals; Aquatic life; Bacteria; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Bacterial physiology; Bacteriology; Decapodiformes - microbiology; Deoxyribonucleic acid; DNA; Extracellular Vesicles - metabolism; Gene Expression Regulation, Bacterial; Gram-negative bacteria; Homology; Host Microbial Interactions; Hydrogen-Ion Concentration; Major outer membrane protein; Membrane proteins; Membrane vesicles; Mutualism; Nutrient content; Pathogenesis; pH effects; Proteins; Proteomics; Proteomics - methods; Regulators; Stimulators; Symbiosis; Transcription; Up-Regulation; Vesicles; Virulence; Virulence factors; Waterborne diseases
• ISSN: 0021-9193; 1098-5530
• DOI: 10.1128/JB.00319-19

Outer membrane vesicles (OMVs) are continuously produced by Gram-negative bacteria and are increasingly recognized as ubiquitous mediators of bacterial physiology. In particular, OMVs are powerful effectors in interorganismal interactions, driven largely by their molecular contents. These impacts have been studied extensively in bacterial pathogenesis but have not been well documented within the context of mutualism. Here, we examined the proteomic composition of OMVs from the marine bacterium , which forms a specific mutualism with the Hawaiian bobtail squid, We found that upregulates transcription of its major outer membrane protein, OmpU, during growth at an acidic pH, which experiences when it transitions from its environmental reservoir to host tissues. We used comparative genomics and DNA pulldown analyses to search for regulators of and found that differential expression of is governed by the OmpR, H-NS, and ToxR proteins. This transcriptional control combines with nutritional conditions to govern OmpU levels in OMVs. Under a host-encountered acidic pH, OMVs become more potent stimulators of symbiotic host development in an OmpU-dependent manner. Finally, we found that symbiotic development could be stimulated by OMVs containing a homolog of OmpU from the pathogenic species , connecting the role of a well-described virulence factor with a mutualistic element. This work explores the symbiotic effects of OMV variation, identifies regulatory machinery shared between pathogenic and mutualistic bacteria, and provides evidence of the role that OMVs play in animal-bacterium mutualism. Beneficial bacteria communicate with their hosts through a variety of means. These communications are often carried out by a combination of molecules that stimulate responses from the host and are necessary for development of the relationship between these organisms. Naturally produced bacterial outer membrane vesicles (OMVs) contain many of those molecules and can stimulate a wide range of responses from recipient organisms. Here, we describe how a marine bacterium, , changes the makeup of its OMVs under conditions that it experiences as it goes from its free-living lifestyle to associating with its natural host, the Hawaiian bobtail squid. This work improves our understanding of how bacteria change their signaling profile as they begin to associate with their beneficial partner animals.