AUTHOR=Xu Wenya , Chen Tao , Wang Huihui , Zeng Weiliang , Wu Qing , Yu Kaihang , Xu Ye , Zhang Xiucai , Zhou Tieli 

TITLE=Molecular Mechanisms and Epidemiology of Fosfomycin Resistance in Staphylococcus aureus Isolated From Patients at a Teaching Hospital in China

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01290

DOI=10.3389/fmicb.2020.01290

ISSN=1664-302X

ABSTRACT=<p><italic>Staphylococcus aureus</italic> is a major cause of hospital- and community-acquired infections placing a significant burden on the healthcare system. With the widespread of multidrug-resistant bacteria and the lack of effective antibacterial drugs, fosfomycin has gradually attracted attention as an “old drug.” Thus, investigating the resistance mechanisms and epidemiology of fosfomycin-resistant <italic>S. aureus</italic> is an urgent requirement. In order to investigate the mechanisms of resistance, 11 fosfomycin-resistant <italic>S. aureus</italic> isolates were analyzed by PCR and sequencing. The genes, including <italic>fosA</italic>, <italic>fosB</italic>, <italic>fosC</italic>, <italic>fosD</italic>, <italic>fosX</italic>, and <italic>tet38</italic>, as well as mutations in <italic>murA</italic>, <italic>glpT</italic>, and <italic>uhpT</italic> were identified. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate the expression of the target enzyme gene <italic>murA</italic> and the efflux pump gene <italic>tet38</italic> under the selection pressure of fosfomycin. Furthermore, multilocus sequence typing (MLST) identified a novel sequence type (ST 5708) of <italic>S. aureus</italic> strains. However, none of the resistant strains carried <italic>fosA</italic>, <italic>fosB</italic>, <italic>fosC</italic>, <italic>fosD</italic>, and <italic>fosX</italic> genes in the current study, and 12 distinct mutations were detected in the <italic>uhpT</italic> (3), <italic>glpT</italic> (4), and <italic>murA</italic> (5) genes. qRT-PCR revealed an elevated expression of the <italic>tet38</italic> gene when exposed to increasing concentration of fosfomycin among 8 fosfomycin-resistant <italic>S. aureus</italic> strains and reference strain ATCC 29213. MLST analysis categorized the 11 strains into 9 STs. Thus, the mutations in the <italic>uhpT</italic>, <italic>glpT</italic>, and <italic>murA</italic> genes might be the primary mechanisms underlying fosfomycin resistance, and the overexpression of efflux pump gene <italic>tet38</italic> may play a major role in the fosfomycin resistance in these isolates.</p>