NanI Sialidase Is an Important Contributor to Clostridium perfringens Type F Strain F4969 Intestinal Colonization in Mice

• Published in: Infection and immunity 2018-12, Vol.86 (12)
• Main Authors: Navarro, Mauricio A, Li, Jihong, McClane, Bruce A, Morrell, Eleonora, Beingesser, Juliann, Uzal, Francisco A
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Bacterial Infections; Clindamycin - pharmacology; Clostridium perfringens - enzymology; Clostridium perfringens - genetics; Female; Gastrointestinal Tract - microbiology; Gene Expression Regulation, Bacterial; Genetic Complementation Test; Loss of Function Mutation; Male; Mice; Mice, Inbred BALB C; Neuraminidase - genetics; Neuraminidase - metabolism; Sialic Acids - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00462-18

type F (formerly enterotoxigenic type A) strains produce an enterotoxin (CPE) to cause acute cases of food poisoning and chronic nonfoodborne human gastrointestinal diseases (NFD), e.g., antibiotic-associated diarrhea (AAD). NFD strains also produce NanI sialidase, an extracellular enzyme that releases sialic acids from sialyated host macromolecules. Recent studies suggested that NanI may contribute to NFD strain intestinal colonization by enhancing the adherence of such strains to intestinal cells and promoting their bacterial growth using generated sialic acid as an energy source. The current study tested this hypothesis by developing a mouse intestinal colonization model involving clindamycin pretreatment to produce conditions mimicking those during AAD. In this model, the type F NFD strain F4969 persisted for at least 4 days in the small intestine, cecum, and colon. When clindamycin-pretreated mice were challenged by oral gavage with equivalent numbers of F4969 bacteria or its isogenic null mutant, significantly lower numbers of the mutant were recovered from all intestinal segments, and it was completely cleared from the small intestine by day 4. Complementation of the mutant to restore NanI production also promoted colonization. When the same null mutant strain was coinoculated into the mouse model together with a -producing strain, the numbers of this mutant were restored to wild-type F4969 levels in all intestinal segments. This result suggests that sialidases produced by other bacteria might also provide some support for intestinal colonization. Collectively, these findings identify NanI to be the first known significant contributor to chronic intestinal colonization by NFD strains.