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

Abstract

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 pathogens1–4. How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella typhimurium and Clostridium difficile, employ 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 the model gut symbiont Bacteroides thetaiotaomicron (Bt) reduces free sialic acid levels resulting in a downregulation of C. difficile’s sialic acid catabolic pathway and 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 possibilities for therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens.

In VitroandIn VivoAntibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection

“…other diseases (5). Therefore, alternative therapeutic methods should be explored in clinical treatment.…”

Ocular Microbiota

“…It is important for normal rats to reach IgA and IgM levels of germ cell-free rats in the lacrimal glands 4 weeks after exposure to environmental factors, suggesting that the local immunity may interact with the ocular flora leading to a direct effect (44). In another study conducted on rats, oral antibiotic treatment reduced secretory IgA levels in tears (45). Immediately after birth, unaffected lacrimal B lymphocyte maturation in rats before opening the eyelids suggests that secretory IgA secretion can be regulated by other mucosal surfaces such as the intestine and nasal mucosa (46).…”

Biome engineering‐2020

“…Different Bifidobacterium or Bacteroides isolates followed different enzymatic strategies of either intracellular or extracellular HMO digestion. The latter strategy allows also bystander bacteria to exploit the liberated sugars (Rakoff‐Nahoum et al ., 2016) with possibilities of cross‐feeding of enteric pathogens (Ng et al ., 2013). Some bifidobacteria showed preferences for fucosylated or small mass HMO typically produced through the first month of lactation (LoCascio et al ., 2007).…”