Antibiotic Susceptibility Influenced by Carbon Source in Bacteroides thetaiotaomicron
Antibiotic therapy causes changes in bacterial abundance and metabolism within the gut microbiome. These changes can lead to complications in the host such as microbiome dysbiosis and opportunistic infections. Additionally, increasing multidrug resistance causes significant morbidity and mortality in patients with bacterial infections. Bacteroides thetaiotaomicron (Bth) is both a normal commensal in the gut and an opportunistic pathogen in other body sites. Our lab has shown that ??-lactam treatment in mice decimates nearly all gut bacterial species except Bth, which experiences a bloom. We propose that in the gut, Bth enters a protected state linked to metabolic changes such as an increase in stress response and polysaccharide fermentation, and a decrease in hexose utilization. Bth is also protected from ??-lactams in vitro when grown on fiber as opposed to glucose. The goal of this project is to understand what mechanism is responsible for this polysaccharide-mediated tolerance (PM-tolerance). Studies of other bacteria show that an increase in respiratory metabolism independent of growth rate promotes susceptibility to bactericidal antibiotics. Bth has a diverse array of metabolic machinery including an electron transport chain (ETC) that works under anaerobic or microaerobic conditions. Transcriptional analysis of Bth treated with the ??-lactam amoxicillin revealed a decrease in ETC enzyme expression when given fiber vs glucose. We found that knocking out different ETC enzymes alters the PM-tolerance phenotype in vitro. Thus, it appears that respiratory capacity is linked to ??-lactam susceptibility in Bth. This work improves upon our understanding of bacterial tolerance strategies and could help identify future therapeutic targets to combat multidrug resistance. Overall design: RNA-seq of Bacteroides thetaiotaomicron grown on two different carbon sources and treated with three different doses of amoxicillin for sixty minutes.