Resistance of Staphylococci to Macrolides-Lincosamides- Streptogramins B (MLSB): Epidemiology and Mechanisms of Resistance

Abstract

A total of 92 genes that confer resistance to MLS antibiotics have been described to date. They can be roughly divided into three groups, depending on the mechanisms by which they confer resistance to one or all of these groups of antibiotics. Three main mechanisms of resistance to MLS antibiotics have been described: methylation of rRNA (target modification), active efflux and inactivation of the antibiotic. Target modification is achieved through the action of the protein product of one of more than 42 different erm (erythromycin rRNA methylase) genes. They confer cross resistance between macrolides, lincosamides and streptogramin B (so-called MLS B resistance) and evoke most concerns. Active efflux and inactivating enzymes (M and L) represent two additional mechanisms of resistance that are targeted only to particular antibiotics or antibiotic classes. Based on the mechanisms of resistance, various resistant phenotypes are expressed. The most prevalent phenotypes are ΜLS B (constitutive or inducible), which is associated with the presence mainly of ermA and ermC genes, followed by the MS B phenotype due to the presence of msrA gene. In livestock S. aureus strains, such as CC 398, other genes such as ermT, lnuA, lsaE and mphC genes are detected.

Phenylpiperazine 5,5-Dimethylhydantoin Derivatives as First Synthetic Inhibitors of Msr(A) Efflux Pump in Staphylococcus epidermidis

“…Although one exception, i.e., the hydoxypropyl derivative 14, is placed in the exact middle of this range, other compounds with the hydroxypropyl linker were totally inactive. This can suggest a beneficial role of the C5-linker, predominant for EPI properties in comparison to either the shorter branched hydroxypropyl linker (12)(13)(14)(15) or the longer one (C6, compound 8).…”

“…The ability of the series of phenylpiperazine 5,5-dimethylhydantoin derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) to enhance the antibacterial activity of erythromycin against both S. epidermidis K/14/1345 and S. epidermidis ATCC 12228 was investigated. The compounds were tested at the sublethal concentrations of 1/4 their respective MICs.…”

“…Based on that interesting outcome, seven phenylpiperazine 5,5-dimethylhydantoins, which were previously tested for their EPI activity in S. aureus pathogen (1-7), were selected for this approach (Table 1). Thus, the compounds (1-7) and their new derivatives synthesized within this study (8)(9)(10)(11)(12)(13)(14)(15), Table 1) were evaluated for the ability to block the Msr(A) efflux pump in S. epidermidis K/14/1345 clinical isolate harboring MS B resistance phenotype.…”

Tackling Multidrug Resistance in Streptococci – From Novel Biotherapeutic Strategies to Nanomedicines

“…Macrolides are the first choice against streptococcal infections in patients allergic to β-lactam ( Kanoh and Rubin, 2010 ) and, clindamycin (lincosamides) has been used for the treatment of infections associated with anaerobic bacteria as an alternative to penicillin G ( Greenwood and Irving, 2012 ). Three main mechanisms have been associated with resistance to these antibiotics: (i) target modification by methylation of rRNA ( erm genes) or target mutations, (ii) active efflux, and (iii) enzymatic inactivation ( Matsuzaki et al, 2005 ; Petinaki and Papagiannitsis, 2018 ). Although most streptococci strains remain sensitive to macrolides and lincosamides, resistance phenotypes have emerged among pyogenic streptococci ( Rato et al, 2013 ; Cattoir, 2016 ; De Greef et al, 2019 ).…”

Exploration of erythromycin ribosomal methylase (erm) genotypes amongst D+ methicillin-resistant Staphylococcus aureus (MRSA) in Sokoto, Nigeria

“…Staphylococcus aureus is among the most prevalent nosocomial pathogens [3] . There is documentation on the treatment of methicillin-resistant Staphylococcus aureus (MRSA) skin infections with macrolidelincosamide-streptogramin B (MLSB) antibiotics [4] . Sometimes resistance to MRSA therapy with erythromycin (macrolide) may extend to clindamycin (lincosamide) and streptogramin B drug classes.…”