Prevention and cure of murineinfection by a Lachnospiraceae strain.

Abstract

We sought to better understand how intestinal microbiota confer protection against() infection (CDI). We utilized gnotobiotic altered Schaedler flora (ASF) mice, which lack the abnormalities of germfree (GF) mice as well as the complexity and heterogeneity of antibiotic-treated mice. Like GF mice, ASF mice were highly prone to rapid lethal CDI, without antibiotics, while very low infectious doses resulted in chronic CDI. Administering such chronic CDI mice an undefined preparation of Clostridia loweredlevels by several logs. Importantly, such resolution of CDI was associated with colonization of Lachnospiraceae. Fractionation of the Clostridia population to enrich for Lachnospiraceae led to the appreciation that its CDI-impeding property strongly associated with a specific Lachnospiraceae strain, namely uncultured bacteria and archaea (UBA) 3401. UBA3401 was recalcitrant to being propagated as a pure culture but could be maintained in ASF mice, wherein it comprised up to about 50% of the intestinal microbiota, which was sufficient to generate a high-quality genomic sequence of this bacterium. Sequence analysis andstudy of UBA3401 indicated that it had the ability to secrete substance(s) that directly impededgrowth. Moreover,administration of UBA3401/ASF feces provided strong protection tochallenge. Thus, UBA3401 may contribute to and/or provide a means to study microbiota-mediated CDI resistance.