Characterization of the Multi-Drug Resistance Gene cfr in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Isolated From Animals and Humans in China

Abstract

We investigated cfr-positive and -negative MRSA strains isolated from animals and humans in different geographical areas of China, from 2011 to 2016. Twenty cfr-positive strains (15.6%) were identified from 128 MRSA strains including 17 from food animals and three from humans. The resistance rates and prevalence of the tested antibiotic resistance genes (ARGs) in the cfr-positive MRSA isolates were higher than that in the cfr-negative MRSA isolates. All cfr-positive MRSA isolates were co-carrying fexA and ermC, and had significantly higher optrA incidence rate vs. the cfr-negative isolates (P < 0.05). In addition, multilocus sequence typing (MLST) assays showed that ST9 and spa-type t899 were the most prevalent ST and spa types in the study strains. However, all of the 20 cfr-positive and 10 randomly selected cfr-negative MRSA isolates were clonally unrelated as determined by pulsed-field gel electrophoresis (PFGE) analyses. Importantly, the cfr gene was successfully transferred to a recipient Staphylococcus aureus strain RN4220 from 13 of the 20 cfr-positive MRSA isolates by electroporation. Among these 13 cfr-positive MRSA isolates, two different genetic contexts surrounding cfr were determined and each was associated with one type of cfr-carrying plasmids. Of note, the predominant genetic context of cfr was found to be a Tn558 variant and locate on large plasmids (∼50 kb) co-harboring fexA in 11 of the 13 MRSA isolates. Furthermore, the cfr gene was also identified on small plasmids (∼ 7.1 kb) that co-carried ermC in two of the 13 MRSA isolates. Our results demonstrated a high occurrence of multi-drug resistance in cfr-positive MRSA isolates, and the spread of cfr might be attributed to horizontal dissemination of similar cfr-carrying transposons and plasmids.

Prevalence and Molecular Determinants of Antimicrobial Resistance in Clinical Isolates of Staphylococcus haemolyticus from India

“…Similar cfr-gene (15.6%; 20/128) presence among the linezolid sensitive LA-MRSA has been reported. 29 Gene expressions in these isolates may have been suppressed by as yet unknown factors. Cfr gene of both linezolid susceptible (3) and resistant isolates (12) were sequenced and submitted to GenBank under the following accession numbers (MN103293-MN103307).…”

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection

“…However, the acquisition of cfr in S. aureus has been associated with low fitness cost that potentially facilitates the growth rates, invasiveness and transmission capacity (LaMarre et al, 2011;Beceiro et al, 2013). In addition, in most of our study MRSA strains, cfr co-expressed with the erm gene (erythromycin resistance) that has a significant correlation with biofilm formations (Beceiro et al, 2013;Li et al, 2018). Previous studies in Enterococcus species exhibited that strong biofilm formation was more prevalent among linezolidresistant compared with -sensitive isolates (Osman et al, 2020).…”

Presence and Characterization of a Novel cfr-Carrying Tn558 Transposon Derivative in Staphylococcus delphini Isolated From Retail Food

“…Tn 558 is a 6.6-kb bacterial transposon. It was first identified on the plasmid pSCFS2 harboring ARG fexA from S. lentus , and then numerous derivatives harboring numerous ARGs were found ( Kehrenberg and Schwarz, 2005 ; Kehrenberg et al, 2007 ; Li et al, 2018 ). With a few exceptions, cfr is often harbored in the Tn558 transposon as coexisting with other ARGs, such as fexA , mecA , erm (A/B/C), tet (K/L/M), and drf (K/G) in the plasmids pSCFS3, pSCFS6, and pSCFS7 in previous studies ( Witte and Cuny, 2011 ), but in this study, the derivative of the Tn 558 transposon harbored cfr , fexA , aacA-aphD , aadD , and ble on the chromosomes.…”

“…Tn 558 is one of these bacterial transposons and was first identified on the plasmid pSCFS2 harboring the antimicrobial resistance gene (ARG) fexA from Staphylococcus lentus ( Kehrenberg and Schwarz, 2005 ). Currently, this transposon is often harbored with cfr , and derivatives of Tn 558 usually carry other acquired ARGs ( Kehrenberg et al, 2007 ; Li et al, 2018 ). Therefore, this transposon plays an important role as vectors in the spread of transposon-borne ARGs.…”