Mining Staphylococcus aureus genomic data for identifying fosfomycin resistance genes
Authors: Yiyi Chen, Yueqin Hong, Lu Sun, Yunsong Yu, Yan Chen
Journal: The Lancet Microbe (2024)

We read with interest the Correspondence by Daniel F Monte and Celso Jose Bruno de Oliveira1Monte DF de Oliveira CJB Global trends in the increasing prevalence of the fosfomycin resistance gene in Staphylococcus aureus.Lancet Microbe. 2023; (published online Nov 10)https://doi.org/10.1016/S2666-5247(23)00339-7Summary Full Text Full Text PDF Scopus (1) Google Scholar in The Lancet Microbe, which describes the increasing prevalence of the fosfomycin resistance gene in Staphylococcus aureus. A previous study indicated the widespread presence of fosA and emphasised the importance of distinguishing the location and origin of fosA (ie, plasmid vs chromosomal and acquired vs intrinsic).2Ito R Mustapha MM Tomich AD et al.Widespread fosfomycin resistance in Gram-negative bacteria attributable to the chromosomal fosA gene.mBio. 2017; 8 (e00749-17)Crossref PubMed Scopus (120) Google Scholar However, names assigned to fosfomycin resistance genes have been inconsistent and have led to confusion in the literature. Consensus on the nomenclature of genes for the fosB gene family is urgently needed. Plasmid-borne fosB variants have been identified in Staphylococcus epidermidis, S aureus, and Enterococcus faecium. In 2023, another chromosomal fosB gene was reported, whose increased expression induced fosfomycin resistance.3Aiezza N Antonelli A Coppi M Di Pilato V Giani T Rossolini GM Up-regulation of resident chromosomal fosB gene expression: a novel mechanism of acquired fosfomycin resistance in MRSA.J Antimicrob Chemother. 2023; 78: 1599-1605Crossref PubMed Scopus (0) Google Scholar This chromosomal fosB gene was designated as fosSA in our study; this gene showed 72% homology with the plasmid-borne fosB and was located adjacent to fosY in the phylogenetic tree4Chen Y Ji S Sun L et al.The novel fosfomycin resistance gene fosY is present on a genomic island in CC1 methicillin-resistant Staphylococcus aureus.Emerg Microbes Infect. 2022; 11: 1166-1173Crossref PubMed Scopus (2) Google Scholar (appendix 1 p 1). The results of analysing the complete genome of S aureus indicate that fosSA is located between the hutG and lysR families. Given the dissimilarity in the amino acid sequence and the position of fosSA compared with that of fosB (appendix 1 p 1), these two genes should be differentiated for further studies evaluating their transmission and evolution. Although the authors highlighted the high prevalence of fosB,1Monte DF de Oliveira CJB Global trends in the increasing prevalence of the fosfomycin resistance gene in Staphylococcus aureus.Lancet Microbe. 2023; (published online Nov 10)https://doi.org/10.1016/S2666-5247(23)00339-7Summary Full Text Full Text PDF Scopus (1) Google Scholar we suggest that the prevalence of fosSA and fosB should be calculated separately. We analysed 15 520 genomes of S aureus from the National Center for Biotechnology Information RefSeq database to present the distribution of fosB and fosSA (appendix 2). The positivity rate was 0·019% for fosB, 0·084% for fosB1, 0% for fosB3, 0·213% for fosB4, 0% for fosB5, and 0·006% for fosB6. Our results showed that fosSA was widely distributed in S aureus, with a positivity rate of 65·2%. In addition, fosSA was frequently identified in predominant clones, including ST5, ST8, and ST239. By contrast, fosSA was rarely identified in ST1, ST59, and ST398 (appendix 1 p 1). Resistance genes fosB, fosD, and fosY might transfer horizontally and spread rapidly as they are situated within mobile genetic elements. In addition, fosSA appears to be intrinsic in some S aureus lineages. Notably, the presence of chromosomal fosB (ie, fosSA) has the potential to influence bacillithiol levels, potentially facilitating the survival of S aureus under oxidative stress.5Posada AC Kolar SL Dusi RG et al.Importance of bacillithiol in the oxidative stress response of Staphylococcus aureus.Infect Immun. 2014; 82: 316-332Crossref PubMed Scopus (55) Google Scholar In addition to its role in fosfomycin resistance, the biological function of fosSA in oxidative stress is crucial and requires further investigation, and the naming of novel fosfomycin resistance genes should be formalised. We declare no competing interests. YiC and YH contributed equally to this work. This study was funded by the National Natural Science Foundation of China (82102434). Download .pdf (.32 MB) Help with pdf files Supplementary appendix 1 Download .xlsx (.61 MB) Help with xlsx files Supplementary appendix 2