A plasmid that encodes three genes for resistance to macrolide antibiotics inStaphylococcus aureus

Abstract

In previous letters, FEMS Microbiol. Lett. 148 (1997) 91-96, it was demonstrated that plasmid pMS97-obtained from a in 1971 clinically isolated Staphylococcus aureus strain MS8968 resistant to macrolide (Mac) antibiotics--carried an msrA gene and uncharacterized erm gene, respectively. msrA encodes a cytoplasmic membrane protein that mediates the so-called 'active Mac-efflux' (designated hereafter as msrSA') and erm encodes a methyltransferase by which a specific adenine residue of 23S rRNA is modified: methylation prevents Mac antibiotics from binding to the 50S ribosomal subunit. Interestingly, we found, in addition, an mph-like gene (hereafter referred to as mphBM) present together with msrSA' and erm on pMS97. By a BLASTP analysis, the gene mphBM product has 49% identity and 67% similarity to the amino acid sequence of MPH(2')II encoded by mphB from Escherichia coli. The order of genes was 5'-msrSA'-mphBM-3', with a 342-base-pair spacer sequence. Although we have not yet determined where erm gene is located on pMS97, the gene seems to be downstream from mphBM. This finding suggests a warning to us concerning the imprudent use of antibiotics.

Macrolides and associated antibiotics based on similar mechanism of action like lincosamides in malaria

“…These resistance mechanisms have not been considered of major clinical importance because enterobacteria are not targets for macrolides. Some clinical isolates of S. aureus produce phosphotransferases, but this event remains rare [ 72 – 74 ]. In pathogenic microorganisms, the impact of the three mechanisms is unequal in terms of incidence and clinical implications.…”

Actinomycetes: A Never-Ending Source of Bioactive Compounds—An Overview on Antibiotics Production

“…Different research groups have recognized a number of enzymatic inactivation processes, which involve the most important antibiotic classes. These chemical transformations comprise hydrolysis, group transfer, and redox (mainly oxidation) reactions [ 29 , 30 , 31 , 32 ].…”

Look and Outlook on Enzyme-Mediated Macrolide Resistance

“…Following this discovery several more enzymes have been found that show a similar activity. These MPHs all mediate the transfer of the γ-phosphate group from GTP onto the macrolide substrates and doing so confer resistance to a group of bacteria ranging from Gram-negative ( E. coli, Pseudomonas, Pasteurella, Klebsiella, Serratia, Shigella ) to Gram-positive ( Staphylococcus ) ( Matsuoka et al, 1998 , 2003 ; Nguyen et al, 2009 ; Ferjani et al, 2012 ; Mendes et al, 2017 ).…”

“…At least 15 gene subtypes of MPHs have been reported, which are designated mph (A) to (O) ( O’Hara et al, 1989 ; Kono et al, 1992 ; Kim et al, 1996 ; Matsuoka et al, 1998 , 2003 ; Roberts et al, 1999 ; Schlüter et al, 2007 ; Pawlowski et al, 2016 , 2018a ). Here, we name their products MPH(2′)-I to MPH(2′)-XV, respectively, with the assumption that all these MPHs phosphorylate the hydroxyl on the C5 linked desosamine or mycaminose moiety, which is present in all macrolides and ketolides that bind to the 23S rRNA where it forms a critical interaction with A2058 (see Figure 2 ).…”