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Publication Abstract from PubMed

The bacterial cell wall plays a key role in viability and is an important drug target. The cell wall is made of elongated polymers that are crosslinked to one another to form a load bearing mesh. An alternate cell wall crosslinking mechanism performed by the L,D-transpeptidase YcbB has been implicated in the stress regulated roles of beta-lactam resistance, outer membrane defect rescue, and typhoid toxin release. The role for this stress linked crosslinking in the context of a host infection was unclear. Here we resolve the crystallographic structures of both S Typhi YcbB and C. rodentium YcbB acylated with ertapenem that delineate the conserved structural characteristics of YcbB. In parallel, we show that the general role of YcbB in peptidoglycan reinforcement under bacterial outer envelope stress does not play a significant role in acute infections of mice by C. rodentium and S Typhimurium. Cumulatively, in this work we provide a foundation for the development of novel YcbB specific antibacterial therapeutics to assist in treatment of increasingly drug resistant S Typhi infections.

Structural and cellular insights into the L,D-transpeptidase YcbB as a therapeutic target in C. rodentium, S. Typhimurium, and S. Typhi infections.,Caveney NA, Serapio-Palacios A, Woodward SE, Bozorgmehr T, Caballero G, Vuckovic M, Deng W, Finlay BB, Strynadka NCJ Antimicrob Agents Chemother. 2020 Nov 2. pii: AAC.01592-20. doi:, 10.1128/AAC.01592-20. PMID:33139287^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.