Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens

Ng KM, Ferreyra JA, Steven K. Higginbottom, Jonathan B. Lynch, Purna C. Kashyap, Smita Gopinath, Natasha Naidu, Biswa Choudhury, Bart C. Weimer, Denise M. Monack and Justin L. Sonnenburg

Nature (2013) 502: 96-9

Speaker: Yu-Chi, Ho (賀聿齊)                                       Time: 15:10~16:00, Feb. 26, 2014

Commentator: Dr. I-Hsiu Huang (黃一修 老師)          Place: Room 601

Abstract:

Human intestine is normally inhabited by a complex microbiota, which provides protection from bacterial infection. Oral antibiotic use often leads to disruption of the gut microbial ecosystem and, consequently, the emergence of opportunistic pathogens like Salmonella spp. and Clostridium difficile (1). Understanding how microbiota assists in protecting the intestine from being harmed by enteric pathogens and how microbiota disruption enables pathogens to initiate disease is important for developing proper prevention and treatment (2). The authors used a common enteric pathogen, Salmonella Typhimurium, to infect gnotobiotic and Bacteroides thetatiotaomicron (Bt, a gut symbiont) colonized mice, respectively. They found that the genes encoding catabolic pathways for sialic acid (nan) and fucose (fuc) were highly expressed in S. Typhimurium after infecting the Bt-colonized mouse, and deletion of both nan and fuc in S. Typhimurium resulted in reduction of its competitiveness in a Bt-dependent manner. Similarly, C. difficile expansion was supported by microbiota-liberated sialic acid in vivo. Further, the Bt mutant deficient in sialidase caused a decrease in free sialic acid level in the gut that lead to downregulation of the sialic acid catabolic pathway and reduced expansion of infecting C. difficile. On the contrary, orally administered exogenous free sialic acid could reverse the decreased expansion of C. difficile. More, the free sialic acid level was elevated in the antibiotic-treated conventional mice; nevertheless, mutants of both S. typhimurium and C. difficile that were unable to catabolize sialic acid exhibited impaired expansion in these mice. Collectively, disruption of resident microbiota by antibiotics could result in increase of the level of mucosal carbohydrates that are utilized by these two enteric pathogens, and lead to their expansion.

References:

1.         Pavia, A. T. et al. Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella. J. Infect. Dis. 161, 255–260 (1990).

2.         Stecher, B. et al. Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria. PLoS Pathog. 6, e1000711 (2010).