Many bacterial infections are caused by diverse microbial communities. These polymicrobial infections often result in higher bacterial burdens and more severe disease than single-species infections, a phenomenon called ?synergy?. While synergy between bacteria has been recognized for over a century, the molecular mechanisms that cause it have proven difficult to elucidate. My laboratory has focused on synergistic interactions between the opportunistic oral pathogen Aggregatibacter actinomycetemcomitans (Aa) and the human oral commensal bacterium Streptococcus gordonii (Sg). In the previous grant cycle, we showed that synergy in Aa/Sg co- infections is caused by several processes involving Aa's utilization of, and response to, the Sg metabolites L- lactate and H2O2. The goal of this renewal is two-fold: 1) to determine how the Aa-Sg synergy mechanisms that we have discovered impact robustness to environmental disturbances and to determine precisely how the spatial organization of these species impacts such interactions during infection (Specific Aims 1 & 2); and 2) to utilize high-throughput genomics to define the metabolic interactions that occur between Aa and a range of co-infecting bacteria (Specific Aim 3).
Many bacterial infections are caused by complex microbial communities, and interactions between community members often enhances disease severity. The primary objective of this research proposal is to define how interaction between bacteria in the oral cavity lead to severe infections both inside and outside the oral cavity. The ultimate goal is to guide development of novel therapeutic strategies that interfere with bacterial interactions during infection.
| Michie, Kelly L; Cornforth, Daniel M; Whiteley, Marvin (2016) Bacterial tweets and podcasts #signaling#eavesdropping#microbialfightclub. Mol Biochem Parasitol 208:41-8 |
| Stacy, Apollo; Abraham, Nader; Jorth, Peter et al. (2016) Microbial Community Composition Impacts Pathogen Iron Availability during Polymicrobial Infection. PLoS Pathog 12:e1006084 |
| Stacy, Apollo; Fleming, Derek; Lamont, Richard J et al. (2016) A Commensal Bacterium Promotes Virulence of an Opportunistic Pathogen via Cross-Respiration. MBio 7: |
| Stacy, Apollo; McNally, Luke; Darch, Sophie E et al. (2016) The biogeography of polymicrobial infection. Nat Rev Microbiol 14:93-105 |
| Estrela, Sylvie; Whiteley, Marvin; Brown, Sam P (2015) The demographic determinants of human microbiome health. Trends Microbiol 23:134-41 |
| Jorth, Peter; Turner, Keith H; Gumus, Pinar et al. (2014) Metatranscriptomics of the human oral microbiome during health and disease. MBio 5:e01012-14 |
| Stacy, Apollo; Everett, Jake; Jorth, Peter et al. (2014) Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection. Proc Natl Acad Sci U S A 111:7819-24 |
| Murray, Justine L; Connell, Jodi L; Stacy, Apollo et al. (2014) Mechanisms of synergy in polymicrobial infections. J Microbiol 52:188-99 |
| Wessel, Aimee K; Hmelo, Laura; Parsek, Matthew R et al. (2013) Going local: technologies for exploring bacterial microenvironments. Nat Rev Microbiol 11:337-48 |
| Jorth, Peter; Trivedi, Urvish; Rumbaugh, Kendra et al. (2013) Probing bacterial metabolism during infection using high-resolution transcriptomics. J Bacteriol 195:4991-8 |
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