Molecular Mechanisms of Drug Resistance in Staphylococcus aureus

Abstract

This paper discusses the mechanisms of S. aureus drug resistance including: (1) introduction. (2) resistance to beta-lactam antibiotics, with particular emphasis on the mec genes found in the Staphylococcaceae family, the structure and occurrence of SCCmec cassettes, as well as differences in the presence of some virulence genes and its expression in major epidemiological types and clones of HA-MRSA, CA-MRSA, and LA-MRSA strains. Other mechanisms of resistance to beta-lactam antibiotics will also be discussed, such as mutations in the gdpP gene, BORSA or MODSA phenotypes, as well as resistance to ceftobiprole and ceftaroline. (3) Resistance to glycopeptides (VRSA, VISA, hVISA strains, vancomycin tolerance). (4) Resistance to oxazolidinones (mutational and enzymatic resistance to linezolid). (5) Resistance to MLS-B (macrolides, lincosamides, ketolides, and streptogramin B). (6) Aminoglycosides and spectinomicin, including resistance genes, their regulation and localization (plasmids, transposons, class I integrons, SCCmec), and types and spectrum of enzymes that inactivate aminoglycosides. (7). Fluoroquinolones (8) Tetracyclines, including the mechanisms of active protection of the drug target site and active efflux of the drug from the bacterial cell. (9) Mupirocin. (10) Fusidic acid. (11) Daptomycin. (12) Resistance to other antibiotics and chemioterapeutics (e.g., streptogramins A, quinupristin/dalfopristin, chloramphenicol, rifampicin, fosfomycin, trimethoprim) (13) Molecular epidemiology of MRSA.

Molecular Basis of Non-β-Lactam Antibiotics Resistance in Staphylococcus aureus

“…The ribosome is a complex molecular machine associated with protein synthesis, and alteration of the drug-binding site through modification of rRNA results in resistance to ribosome-targeting antibiotics. For example, modification of the bacterial ribosome by 23S rRNA methyltransferase [ 40 ] prevents the binding of macrolides to ribosomal targets [ 31 , 32 ]. Methylation of 23S rRNA by chloramphenicol-florfenicol resistance ( cfr ) gene encoded rRNA methyltransferase alters the drug-binging site 50S ribosomal subunit [ 41 ], thus reducing the ability of chloramphenicol and clindamycin antibiotics to inhibit the ribosomes translational activity.…”

Genomic Insights of First ermB-Positive ST338-SCCmecVT/CC59 Taiwan Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus in Poland

“…Resistance to aminoglycosides is associated with the presence of aminoglycoside-modifying enzyme genes: aph (3′)-III and ant (6)-I. Resistance to tetracyclines is expressed due to MFS efflux pump genes: tet K and tet 38 [ 20 , 40 ]. The cMLS-B phenotype correlates with the presence of erm B gene cluster consisting of the erm B gene, its leader peptide regulatory region erm BL and an additional erm B-AP CDS, which encodes a peptide of unknown function [ 41 , 42 ].…”

“…Until recently, the main determinants of erm A and erm C of the MLS-B phenotype have been dominant among Polish MRSA strains. The erm B gene has been most often found in Gram-negative rods, Streptococcus spp., and Enterococcus species [ 20 ]. This study is the first description of the erm B-positive MRSA strain from Poland.…”

“…Whereas, erm B is much less frequent. Until now, the erm B gene has been described primarily in Gram-negative rods and has dominated in resistant variants of Streptococcus and Enterococcus [ 20 , 21 , 22 , 23 ].…”

Nickel Nanoparticles: Applications and Antimicrobial Role against Methicillin-Resistant Staphylococcus aureus Infections

“…Methicillin-resistant S. aureus (MRSA) is among the leading causes of nosocomial pathogens which decipher the multidrug-resistance (MDR) phenotype [ 1 , 2 , 3 ]. MRSA employs various mechanisms to resist drugs, such as cell wall thickening, efflux of compounds, enzymatic destruction, and target variation [ 4 , 5 , 6 ].…”