Fosfomycin Resistance: An Update on the Anthropogenic Impact Through Agriculture

Abstract

The extensive and often inappropriate use of antibiotics has led to the rapid emergence and spread of antibiotic resistance, reducing their effectiveness against pathogenic microorganisms. Fosfomycin has become an increasingly important therapeutic option in both human and veterinary medicine, particularly when other antibiotics fail. This review summarises current knowledge on the occurrence of fosfomycin resistance and evaluates the role of agricultural practices in its dissemination. Multiple microbial resistance mechanisms have been identified, including genes from the fosA, fosB, and fosC families, and new determinants continue to be reported. Agriculture contributes to the environmental spread of resistance through the use of antibiotics in food-producing animals, the exchange of resistant microorganisms between humans and animals, and the application of manure as fertiliser. Fosfomycin resistance genes have been detected in livestock such as pigs, chickens, pigeons, and cows, as well as in vegetables. Their presence in soil is influenced by fertilisation, nitrogen levels, microplastics, heavy metals, and pesticide application. Additionally, climate warming may facilitate the broader dissemination of fosfomycin resistance. Despite increasing evidence, current understanding remains limited. Further research is needed to elucidate the mechanisms driving the spread of fosfomycin resistance in agricultural environments and to develop effective monitoring strategies.

Keywords: animal husbandry; antibiotic resistance; fertilisation; fosfomycin; heavy metals; microplastics; pesticides; resistome; soil microbiota; soil pollution.

Figure 1

Chemical structure of fosfomycin (A), fosfomycin, disodium (B), fosfomycin calcium (C), and fosfomycin trometamol (D). The dot represents ionic interactions between fosfomycin and trometamol [20].

Figure 2

Uptake and mechanism of action of fosfomycin (fosfomycin—yellow circles) (A) and major mechanisms contributing to fosfomycin resistance (B), MurA* denotes a mutated form of MurA with reduced affinity for fosfomycin.