Selective inhibition of Neisseria gonorrhoeae by a dithiazoline in mixed infections with Lactobacillus gasseri.

Selective inhibition of Neisseria gonorrhoeae by a dithiazoline in mixed infections with Lactobacillus gasseri. Antimicrob Agents Chemother. 2018 Oct 01;: Authors: Lenz JD, Shirk KA, Jolicoeur A, Dillard JP Abstract The Gram-negative human pathogen Neisseria gonorrhoeae has progressively developed resistance to antibiotic monotherapies, and recent failures of dual-drug therapy have heightened concerns that strains resistant to all available antibiotics will begin circulating globally. Targeting bacterial cell wall assembly has historically been effective at treating infections with N. gonorrhoeae, but as the effectiveness of β-lactams (including cephalosporins) are challenged by increasing resistance, research has expanded into compounds that target the numerous other enzymes with roles in peptidoglycan metabolism. One example is the dithiazoline compound JNJ-853346 (DTZ), which inhibits the activity of an E. coli serine protease L,D-carboxypeptidase (LdcA). Recently, the characterization of an LdcA homolog in N. gonorrhoeae revealed localization and activity differences from the characterized E. coli LdcA, prompting us to explore the effectiveness of DTZ against N. gonorrhoeae We found that DTZ is effective at inhibiting N. gonorrhoeae in all growth phases, unlike the specific stationary-phase inhibition seen in E. coli Surprisingly, DTZ does not inhibit gonococcal LdcA enzyme activity, nor is DTZ sensitivity significantly decrease...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research