Post antibiotic treatment expansion of pathogenic gut microbes induced by availability of oxidised sugars
Creators: name: Ng, Wenfa
Publisher: name: figshare
Year: 2016
Subjects: subject: Biochemistry
subject: Molecular Biology
subject: Microbiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences

description: Development of resistance to antibiotics treatment is a concept familiar to scientists and the general public through frequent news reports and feature articles in the popular media. In general a phenomenon where bacteria enter into a quiescent state known as persistence or a metabolic program called stringent response, or through acquisition of genetic repertoire conferring resistance to antibiotics, it came about usually through the non completion of a course of antibiotic treatment, where subpopulations of bacteria that survive the initial rounds of treatment are able to obtain nutrients more effectively due to lack of competition from other vulnerable microbial species vanquished by antibiotics. However, possibility exists where certain strains of bacteria may harbour resistance genes capable of countering the effects of antibiotics through a combination of efflux pumps or mutation of original drug target, which can therefore survive a completed course of antibiotic treatment. Not restricted to either broad spectrum or narrow spectrum antibiotics treatment, such populations of bacteria, however small in numbers at the start, could expand into the dominant species of a microhabitat in the body, and portends significant risk to the host if it is a pathogenic strain. Known as post-antibiotic treatment expansion of pathogenic species, the issue holds significant implications to the design of antibiotics, selection of potential drug targets to reduce chances of evolution of resistance, and the tailoring of antibiotic treatment to the individual in terms of both drug combinations, sequence of antibiotic administration, and duration of treatment. Tackling the question in a hypothesis driven manner, Baumler and coworkers examined the host factors that indirectly facilitated an expansion of a pathogenic strain of <i>Salmonella</i> Typhimurium in research reported in “Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion”, Link. Specifically, the researchers hypothesized that greater availability of oxidized sugars such as aldehydes and alcohols could provide increased nutrients allowing the proliferation of pathogenic <i>S</i>. Typhimurium in the gut of mouse after antibiotic treatment. Using a gene construct encoding proteins important to the import of galactarate, recombinant <i>S</i>. Typhimurium was constructed, and uptake of oxidized glucose (i.e., glucarate) and oxidized galactose (i.e., galactarate) followed by their subsequent fermentation is confirmed. But, where does the oxidizing power for glucarate and galactarate comes from? The authors answered through animal model research where they showed through gas chromatography mass spectrometry that reactive nitrogen species released by inducible nitric oxide synthase (iNOS) of mouse most likely oxidized glucose into glucarate; thereby, presenting the gut microbiota with a selection pressure that favours the growth of pathogenic <i>S</i>. Typhimurium able to uptake and ferment glucarate. Inhibition of iNOS through addition of inhibitors was observed to significantly dent the population expansion of <i>S</i>. Typhimurium, which highlights the essentiality of glucarate and galactarate uptake and fermentation in conferring a fitness advantage to the pathogenic species. Thus, the research outlines a mechanism whereby antibiotic treatment could lead to elevated reactive nitrogen species in the gut that alters the nutritional balance in a way that favours pathogenic species over commensal ones. However, the critical link between why antibiotic could activate nitric oxide synthase signalling pathway in the host remains mechanistically unknown. Solving it could provide important details on the selection of specific type of antibiotics that would not result in a cascade of events that lead to post antibiotic treatment expansion of dangerous pathogens that could permanently alter the dynamics of the gut microbiota. Collectively, the reported research opens microbiologists’ eyes to how a benign and efficacious antibiotic such as streptomycin could potentiate an expansion of a resident pathogenic strain of <i>Salmonella</i> sp. through induction of an important host broad spectrum signalling cascade, that results in greater quantities of a metabolite that only the pathogenic and drug resistant strains could ferment; thereby, yielding a population expansion that changed gut microbiota dynamics. <br>