Enteric Pathogens Expand After Antibiotic Treatment

They investigated why two potentially deadly pathogens can get a foothold in the forbidding environment of the gut following antibiotic treatment.

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.

As soon as these two parasitic invaders have multiplied to sufficient numbers, they induce inflammation. While inflammation is not a good environment for restoring good bacteria, C. difficile and S. typhimurium thrive in it. The scientists introduced a single bacterial strain Bacteroides thetaiotaomicron into germ-free animal. This friendly bacterial strain resides in the gut of normal mice and humans. B. thetaiotaomicron has enzymes that pry sugar molecules from the mucus chains dangling from the intestinal lining, but lacks the enzymes to break down the molecules that make up sialic acid. However, in a normal gut there are several other microbes that can break down the sialic acid and fucose molecules. A normal gut is full of microbes that can split foods that B. thetaiotaomicron cannot, but needs.

Justin Sonnenburg, PhD, the senior author of the study said, “The bad guys in the gut are scavenging nutrients that were liberated by the good guys, who are casualties of the collateral damage incurred by antibiotics. Antibiotics cause our friendly gut bacteria to unwittingly help these pathogens. Our work shows how they go about it after a dose of antibiotics. They take advantage of a temporary spike in available sugars liberated from intestinal mucus left behind by slain commensal microbes."

The team concluded that one day a medication that inhibits the enzymes used by friendly gut bacteria to liberate sialic acid from mucus could be created, thus depriving the pathogens of their nutrients. The medication could then be given alongside antibiotics. They added that probiotics in the form of bacterial strains that digest sialic acid rapidly could also achieve a similar effect. The study was published on September 1, 2013, in the journal Nature.

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