Sunday, 27 October 2013

Antibiotic-associated pathogen infection

The intestinal microbiota provide protection from bacterial infections. However, when disturbed with oral antibiotics, microbiota protection is disrupted, allowing the emergence of several pathogens. How do these pathogens capitalize on the failure of the protection provided by the microbiota?

Two antibiotic-associated pathogens, S. typhimurium and C. difficile, use a common strategy of catabolizing microbiota-liberated mucosal carbohydrates to facilitate their expansion within the gut (Nature, Sept. 2013).

The paper, by Katharine M. and colleagues, is titled "Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens".

The abstract reads:

"The human intestine, colonized by a dense community of resident microbes, is a frequent target of bacterial pathogens. Undisturbed, this intestinal microbiota provides protection from bacterial infections. Conversely, disruption of the microbiota with oral antibiotics often precedes the emergence of several enteric pathogens1, 2, 3, 4. How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella enterica serovar Typhimurium (S. typhimurium) and Clostridium difficile, use a common strategy of catabolizing microbiota-liberated mucosal carbohydrates during their expansion within the gut. S. typhimurium accesses fucose and sialic acid within the lumen of the gut in a microbiota-dependent manner, and genetic ablation of the respective catabolic pathways reduces its competitiveness in vivo. Similarly, C. difficile expansion is aided by microbiota-induced elevation of sialic acid levels in vivo. Colonization of gnotobiotic mice with a sialidase-deficient mutant of Bacteroides thetaiotaomicron, a model gut symbiont, reduces free sialic acid levels resulting in C. difficile downregulating its sialic acid catabolic pathway and exhibiting impaired expansion. These effects are reversed by exogenous dietary administration of free sialic acid. Furthermore, antibiotic treatment of conventional mice induces a spike in free sialic acid and mutants of both Salmonella and C. difficile that are unable to catabolize sialic acid exhibit impaired expansion. These data show that antibiotic-induced disruption of the resident microbiota and subsequent alteration in mucosal carbohydrate availability are exploited by these two distantly related enteric pathogens in a similar manner. This insight suggests new therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens."

For further information on this topic, see Qiagen.

Posted by Tim Sandle

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