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Infectious Diseases - Microbiology - Pharmacology - Science Policy

Sub-Inhibitory Cefsulodin Sensitization of E. coli to ß-lactams Is Mediated by PBP1b Inhibition
Published: Tuesday, November 06, 2012
Author: Sujoy K. Sarkar et al.

by Sujoy K. Sarkar, Mouparna Dutta, Akash Kumar, Dhriti Mallik, Anindya S Ghosh

The combination of antibiotics is one of the strategies to combat drug-resistant bacteria, though only a handful of such combinations are in use, such as the ß-lactam combinations. In the present study, the efficacy of a specific sub-inhibitory concentration of cefsulodin with other ß-lactams was evaluated against a range of Gram-negative clinical isolates. This approach increased the sensitivity of the isolates, regardless of the ß-lactamase production. The preferred target and mechanism of action of cefsulodin were identified in laboratory strains of Escherichia coli, by examining the effects of deleting the penicillin-binding protein (PBP) 1a and 1b encoding genes individually. Deletion of PBP1b was involved in sensitizing the bacteria to ß-lactam agents, irrespective of its O-antigen status. Moreover, the use of a sub-inhibitory concentration of cefsulodin in combination with a ß-lactam exerted an effect similar to that one obtained for PBP1b gene deletion. We conclude that the identified ß-lactam/cefsulodin combination works by inhibiting PBP1b (at least partially) despite the involvement of ß-lactamases, and therefore could be extended to a broad range of Gram-negative pathogens.