High prevalence and global distribution of fosfomycin resistance genes in Salmonella serovars

Fosfomycin, an old antimicrobial agent with a broad spectrum of activity, has been reintroduced into clinical use for the treatment of patients with difficult-to-treat-infections,1Falagas ME Vouloumanou EK Samonis G Vardakas KZ Fosfomycin.Clin Microbiol Rev. 2016; 29: 321-347Crossref PubMed Scopus (356) Google Scholar including those due to carbapenem-resistant Enterobacterales.2Doi Y Treatment options for carbapenem-resistant Gram-negative bacterial infections.Clin Infect Dis. 2019; 69: S565-S575Crossref PubMed Scopus (309) Google Scholar However, fosfomycin-resistant bacterial strains (including Salmonella spp) have emerged and spread, potentially posing a crucial threat to public health3Ito R Mustapha MM Tomich AD et al.Widespread fosfomycin resistance in gram-negative bacteria attributable to the chromosomal fosA gene.MBio. 2017; 8: e00749-e00817Crossref Scopus (108) Google Scholar as Salmonella spp are a major culprit of diarrhoeal and invasive diseases globally and fosfomycin represents an attractive treatment option.4Feasey NA Dougan G Kingsley RA Heyderman RS Gordon MA Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa.Lancet. 2012; 379: 2489-2499Summary Full Text Full Text PDF PubMed Scopus (668) Google Scholar, 5Popa GL Papa MI Salmonella spp infection—a continuous threat worldwide.Germs. 2021; 11: 88-96Crossref Scopus (38) Google Scholar We therefore tested whether fosfomycin resistance in Salmonella spp is a substantial concern for the One Health framework by analysing 550 780 publicly available Salmonella spp genomes in the NCBI Pathogen Detection system. Alarmingly, we uncovered a high prevalence of fosfomycin resistance genes among Salmonella spp strains, with a total of 26 165 strains harbouring at least one fosA-group fosfomycin resistance gene encoding glutathione S-transferase. Specifically, the identified genes were fosA7 (n=13963), fosA7.2 (n=5247), fosA3 (n=3762), fosA7.3 (n=2453), and fosA7.4 (n=740). Of these Salmonella spp strains, 21 were Salmonella enterica subsp salamae. The remaining strains fell under Salmonella enterica subsp enterica and were further subdivided into 73 distinct serovars (appendix p 2–3). 36 of these serovars were rare and were reported for the first time in this Correspondence (appendix p 4–5). Upon comprehensive examination of the global distribution of Salmonella spp strains carrying fosfomycin resistance genes, our genomic analysis revealed their presence across 47 countries, spanning six continents (appendix p 6). This distribution indicates a global problem and raises concerns about the potential effect of fosfomycin resistance on public health within the One Health framework. The emergence and spread of fosfomycin-resistant Salmonella strains poses a crucial threat, as they restrict treatment options for this common infection and could lead to increased morbidity and mortality rates. The effectiveness of antimicrobial therapy has already been threatened by the emergence and expansion of antimicrobial-resistant Salmonella serovars.6da Silva KE Tanmoy AM Pragasam AK et al.The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study.Lancet Microbe. 2022; 3: e567-e577Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Understanding the mechanisms underlying fosfomycin resistance in Salmonella spp is crucial for developing strategies to combat this problem. Further research is needed to investigate the genetic determinants responsible for the widespread dissemination of fosfomycin resistance genes in these bacteria. The identification of these genes provides valuable insights into the molecular basis of resistance, which could inform the design of new therapeutic approaches or the enhancement of existing antibiotic therapies. Moreover, efforts to monitor and control the spread of fosfomycin-resistant Salmonella strains should be intensified, with a focus on enhancing surveillance systems and implementing stringent infection control measures. A One Health approach is particularly relevant in this context, as antibiotic resistance is a complex issue that transcends human, animal, and environmental boundaries. Collaborative efforts between human and veterinary medicine, agriculture, and environmental sectors are vital to effectively address this growing problem. The findings presented in this Correspondence underscore the substantial importance of fosfomycin resistance in Salmonella spp within a One Health framework. The high prevalence and global distribution of fosA resistance genes among Salmonella serovars raise serious public health concerns and necessitate immediate action to preserve the effectiveness of antibiotics and protect human and animal health worldwide. This research was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (Food Research Center 2013/07914–8 and 2016/03044–7). NL is a research fellow of CNPq (314336/2021-4). The other authors declare no competing interests. Download .pdf (.27 MB) Help with pdf files Supplementary appendix