Project Summary The discovery of antibiotics greatly decreased the public health burden associated with bacterial infections; however, antibiotics also disrupt the beneficial microbiome. An added challenge is that the efficacy of treatments is often not what is seen in the laboratory setting in part due to the fact bacteria live in mixed microbial populations. While some mechanisms of community protection have been well studied such as degradation or sequestration of the antibiotic, significantly less effort has gone into understanding the ways that physiological changes protect the cells. Efforts to study mixed microbial systems often use synthetic communities where interactions are dominated by nutrient competition and stress response pathways. To address these issues, our laboratory uses a naturally formed community of lactic acid bacteria and Acetobacter that is highly reproducible form natural environments and displays coevolved properties. Recently we have shown that the beneficial microbe Lactiplantibacillus plantarum has a difference in antibiotic sensitivities when grown in a mixed microbial community with Acetobacter species compared to when it is grown as an isolated strain. Previous work has focused on how these microbes engage in cross feeding; however little work has gone into understanding how non-nutritional cues might affect cellular physiology. My research aims to close this gap by understanding how L. plantarum and Acetoabcter coordinate growth to modify physiology and sensitivity to antibiotics. Leveraging the chemically defined media I co-created, I have recapitulated this antibiotic sensitivity change with the addition of the small molecule acetate which is produced by Acetobacter. Additionally, I have seen that acetate stimulates the growth of L. plantarum. This work led me to identify a mutant of L. plantarum that can grow fast without the stimulation of acetate. Through a combination of genetic, metabolomic, and microscopic approaches I will identify the underlying molecular mechanism of the phenotype. This project will identify how a cross-phylum signals affect cellular physiology which may have implications across bacterial species to understanding how antibiotic sensitives are modulated by mixed microbial communities.