Chimeric Amphiphilic Disinfectants: Quaternary Ammonium/Quaternary Phosphonium Hybrid Structures.

Cationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium-phosphonium structures. Compounds were obtained in two steps and good yields, with straightforward and chromatography-free purifications. Antibacterial activity evaluation of these compounds against a panel of seven bacterial strains, including two MRSA strains as well as opportunistic pathogen A. baumannii, were encouraging, as low micromolar inhibitory activity was observed for multiple structures. Alkyl chain length on the ammonium group was, as expected, a major determinant of bioactivity. In addition, high therapeutic indexes (up to 125-fold) for triphenyl phosphonium-bearing amphiphiles were observed when comparing antimicrobial activity to mammalian cell lysis activity.

Genetic mechanisms governing sporulation initiation in Clostridioides difficile.

As an anaerobe, Clostridioides difficile relies on the formation of a dormant spore for survival outside of the mammalian host's gastrointestinal tract. The spore is recalcitrant to desiccation, numerous disinfectants, UV light, and antibiotics, permitting long-term survival against environmental insults and efficient transmission from host to host. Although the morphological stages of spore formation are similar between C. difficile and other well-studied endospore-forming bacteria, the C. difficile genome does not appear to encode many of the known, conserved regulatory factors that are necessary to initiate sporulation in other spore-forming bacteria. The absence of early sporulation-specific orthologs suggests that C. difficile has evolved to control sporulation initiation in response to its unique and specific ecological niche and environmental cues within the host. Here, we review our current understanding and highlight the recent discoveries that have begun to unravel the regulatory pathways and molecular mechanisms by which C. difficile induces spore formation.