Browsing by Author "Slavic, Lauren E"

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    The Effect of Cross-Feeding on the Evolution of Antibiotic Persistence and Resistance
    (2023-05-01) Slavic, Lauren E
    Antibiotic resistance is an urgent global public health threat, as resistant bacteria can overcome antibiotic stress by being able to grow despite treatment. Two other strategies also contribute to antibiotic failure – antibiotic tolerance describes the process of dying more slowly to antibiotic exposure, whereas antibiotic persistence describes the survival of a tolerant subpopulation of bacterial cells. These strategies are often overlooked, despite their importance and contribution towards the development of full resistance mutations. Previous studies fail to consider that bacteria tend to live in microbial communities, often participating in mutualistic ecological interactions through cross-feeding nutrient exchange. Although cross-feeding is ecologically important, its effects on the rates and mechanisms of antibiotic persistence are unknown. In addition, evolution studies in shaken liquid cultures often overlook the importance of bacterial distribution within an ecological environment, where most natural microbial communities are considered to be spatially structured on surfaces and participate in localized interactions. I studied whether cross-feeding interactions affect the evolution of antibiotic persistence and concurrent resistance in Escherichia coli evolved in monoculture and in synthetic cross-feeding mutualism with Salmonella enterica in shaken liquid and spatially structured conditions. After 10 cycles of cyclical exposure to short-term ampicillin treatment and drug-free growth, evolutionary rate, subsequent resistance, mutational profile, and underlying genetic mechanisms could be analyzed. I found that cross-feeding alone did not significantly alter the evolution of persistence or resistance, as both monocultures and co-cultures showed similar 100-fold increases in persistence, with underlying lag time contributing mechanisms. While I observed similar numbers of persistence-associated mutations in both conditions, monoculture-evolved mutations were enriched in amino acid transport and mutualistic-evolved mutations were enriched in tRNA synthesis. I found that cross-feeding, in combination with spatial structure, was found to increase persistence. Incomplete results do not show concurrent resistance evolution, but are hypothesized. This result suggests that ecological interactions and spatial structure can shape the rate and mechanisms underlying the evolution of survival.