Vol.72 No.6 November 2024
Fosfomycin: Prospects of new ways to combat multidrug-resistant bacteria
1)Department of Bacteriology, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, Japan
Abstract
The spread of bacterial resistance to quinolones, β-lactams, and other antimicrobials used commonly in healthcare settings has become a major social issue as the rates of resistance to these drugs continue to remain high. In this context, the potential demand for fosfomycin (FOM) is rising again. This is because, in addition to its broad antibacterial spectrum, FOM does not exhibit cross-resistance to other categories of antibacterial agents, including quinolones and β-lactams, and is therefore expected to be a last resort drug against multidrug-resistant bacteria. Furthermore, FOM has stronger antibacterial activity in microaerophilic and anaerobic environments, such as those found inside biofilms and adjacent tissues.
The antibacterial activity of FOM depends on the transport activity and expression levels of the uptake transporters GlpT and UhpT, in addition to those of the inactivating enzyme and target molecule MurA (cell wall synthase). Many research groups, including the authors, have shown that the expression levels of GlpT and UhpT vary depending on various environmental factors, host and bacterial metabolites, regulatory factors, etc. Factors affecting the antimicrobial activity of FOM, including regulators of GlpT and UhpT expression, and their molecular mechanisms, are now being investigated. A better understanding of the factors and molecular mechanisms that influence the antimicrobial activity of FOM, including regulators of GlpT and UhpT expression, is expected to lead to improved treatment protocols to predict the emergence of resistant strains and to enhance the usefulness of this drug.
In this paper, the above findings that have been elucidated to date will be discussed, including the latest research trends.
Key word
FOM, drug resistance, biofilm, resistance gene, Escherichia coli
Received
May 29, 2024
Accepted
July 29, 2024
Jpn. J. Chemother. 72 (6): 561-567, 2024
