Revista Mexicana de Ingeniería Química, Vol. 23, No. 1 (2024), Bio24101

Genes involved in an antibiotic resistance system in Streptomyces clavuligerus

V. Sicairos-Díaz, P. Liras,  A. G. Reyes,  F.J. Calderón-de la Sancha, J. Barrios-González, C. Millán-Pacheco, A. Mejía

https://doi.org/10.24275/rmiq/Bio24101

 

Abstract

The cephamycin C gene cluster in Streptomyces clavuligerus contains the genes cmcT, bla and pbp74, which have been suggested to be involved in antibiotic resistance. To evaluate the role of these genes, mutants of S. clavuligerus ATCC 27064 deleted in pbp74 and cmcT have been constructed. The resistance of these mutant strains as well as S. clavuligerus Dbla::aphII, a bla-deleted mutant, to cephalosporin and penicillin G have been analyzed. A 11% increase in resistance to penicillin G was detected when the cmcT gene was deleted compared to parental strain. Disruption of bla and pbp74 increased penicillin G sensitivity. Cephamycin C production was 83% lower in the cmcT-deleted mutant, however, bla-deleted mutant, the production was enhanced 193% compared to the parental strain. Genes expression was measured by qRT-PCR. In addition, the CmcT, Bla and Pbp74 proteins were modeled and their affinity for antibiotics was assessed. Based on our results, these three genes present in S. clavuligerus are suggested to be part of a self-defense system. Enhancement of cephamycin C production with the interruption of the bla gene was an interesting discovery which could be applied to improve the production of this antibiotic.

Keywords: Actinobacteria, β-lactam antibiotics resistance, Cephamycin, clavulanic acid, beta-lactam antibiotics

 

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