Author : Andrés Jesus Aranda-Díaz
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (124 download)
Book Synopsis Probing Gut Bacterial Physiology and Antibiotic Action in Complex Environments by : Andrés Jesus Aranda-Díaz
Download or read book Probing Gut Bacterial Physiology and Antibiotic Action in Complex Environments written by Andrés Jesus Aranda-Díaz and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: For decades, research on bacterial physiology has been conducted in standardized conditions in monocultures, ignoring the natural community context of most species. As a result, predicting the effect of perturbations such as antibiotics on gut microbial communities remains highly challenging despite its paramount importance. Mechanistic understanding of human gut microbiota ecology has also been hampered by limited throughput and the fact that key parameters often cannot be precisely tuned or measured in animal models. During this PhD, I developed tools and systems to interrogate bacterial physiology in complex communities and within animal hosts, and used these tools to make seminal discoveries regarding how life in a community alters the behaviors of individuals. The gut microbiota of the laboratory fruit fly is a low diversity consortium with 5 bacterial species from the Lactobacillus and Acetobacter genera, all of which can be cultured in vitro. I leveraged the simplicity and manipulability of this microbiota to study the role of metabolic cross feeding on growth and antibiotic action. Using in vitro synthetic communities composed of Lactobacillus and Acetobacter species, I discovered non-canonical tolerance to rifampin and erythromycin that is induced by interspecies interactions and mediated by changes in pH due to metabolic cross-feeding. Additionally, I developed imaging techniques to visualize individual bacterial cells within live fruit flies, opening the door to studying single-cell bacterial physiology within intact hosts. To enable quantitative, systematic experimentation on the human gut microbiota, I developed culturing techniques to directly compare responses in vitro and in humanized mice. I compared the sensitivity of gut commensals in vitro and in humanized mice to explore the role of heterogeneous environments and community composition in antibiotic action. I then cultured hundreds of communities that resemble the human gut microbiota using fecal samples as inocula for high-throughput liquid culturing. In vitro antibiotic treatment of these communities recapitulated changes observed in vivo in mice, and uncovered different modes of recovery, highlighting the capabilities of this methodology. .