Int J Antimicrob Agents. 2023 Nov 3:107027.
T Gil-Gil, JL Martínez
Abstract
The inducible transporters UhpT and GlpT are accepted as the unique fosfomycin inner membrane cellular transporters. Accordingly, it has been traditionally accepted that fosfomycin activity is enhanced in the presence of the substrate of the UhpT transporter, glucose-6-phosphate. Previous work suggests that other transporters, the fructose phosphotransferase system (PTS), could be involved in the fosfomycin transport in the bacterial species Stenotrophomonas maltophilia. In this paper we address the potential activity of this system as fosfomycin transporters in Escherichia coli, bacterial pathogen in which the fosfomycin transport has been deeply studied and characterized. Notably, we found that the deletion of both fructose specific- and general- PTS system proteins in E. coli increases fosfomycin resistance, which could indicate that fructose PTS is involved in fosfomycin transport in E. coli. Further, while UhpT (the canonical fosfomycin transport) inactivation in E. coli increases fosfomycin resistance by 2-fold, inactivation of genes encoding the PTS increases it up to 256-fold. Moreover, although intracellular accumulation declines when each of both transporters is absent, the decline is larger in the case of mutations in the PTS system. The results presented in this study re-open the study of fosfomycin transport and reveal the role of the PTS transport system in the transport of this bactericidal antibiotic in E. coli.
Keywords: Escherichia coli; antibiotic transport; fosfomycin.
doi: 10.1016/j.ijantimicag.2023.107027.