Search

Leveraging systems biology approaches, we illustrate how metabolically distinct species of Clostridia protect against or worsen Clostridioides difficile infection in mice by modulating the pathogen's colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Paraclostridium bifermentans survive infection with reduced disease severity, while mice colonized with the butyrate-producer, Clostridium sardiniense, succumb more rapidly. Systematic in vivo analyses revealed how each commensal alters the gut-nutrient environment to modulate the pathogen's metabolism, gene regulatory networks, and toxin production. Oral administration of P. bifermentans rescues conventional, clindamycin-treated mice from lethal C. difficile infection in a manner similar to that of monocolonized animals, thereby supporting the therapeutic potential of this commensal species. Our findings lay the foundation for mechanistically informed therapies to counter C. difficile disease using systems biology approaches to define host-commensal-pathogen interactions in vivo., Competing Interests: Declaration of interests L.B. and G.K.G. are co-inventors on patents for C. difficile microbiota therapeutics. L.B., G.K.G., and A.L.S. are SAB members and hold stock in ParetoBio. G.K.G.is an SAB member and holds stock in Kaleido, Inc. A.L.S. is a co-owner of ExArca Pharmaceuticals. The remaining authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A recent study explains how bacterial spores capture and protect phage DNA, which remains free in the host cytoplasm but is unable to initiate the virulence pathway that leads to lysis of actively growing bacterial cells.

Recent studies have shown that, early during sporulation in Bacillus subtilis, the temporary exclusion of 70% of the chromosome from the forespore compartment is critical to the regulated activation of two major transcription factors, sigma(F) and sigma(E).