Predicted transmembrane proteins with homology to Mef(A) are not responsible for complementing mef(A) deletion in the mef(A)–msr(D) macrolide efflux system in Streptococcus pneumoniae

Abstract

Objectives In streptococci, the type M resistance to macrolides is due to the mef(A)–msr(D) efflux transport system of the ATP-Binding cassette (ABC) superfamily, where it is proposed that mef(A) codes for the transmembrane channel and msr(D) for the two ATP-binding domains. Phage ϕ1207.3 of Streptococcus pyogenes, carrying the mef(A)–msr(D) gene pair, is able to transfer the macrolide efflux phenotype to Streptococcus pneumoniae. Deletion of mef(A) in pneumococcal ϕ1207.3-carrying strains did not affect erythromycin efflux. In order to identify candidate genes likely involved in complementation of mef(A) deletion, the Mef(A) amino acid sequence was used as probe for database searching. Results In silico analysis identified 3 putative candidates in the S. pneumoniae R6 genome, namely spr0971, spr1023 and spr1932. Isogenic deletion mutants of each candidate gene were constructed and used in erythromycin sensitivity assays to investigate their contribution to mef(A) complementation. Since no change in erythromycin sensitivity was observed compared to the parental strain, we produced double and triple mutants to assess the potential synergic activity of the selected genes. Also these mutants did not complement the mef(A) function.

Successful Intra- but Not Inter-species Recombination of msr(D) in Neisseria subflava

“…In our previous study, we found that the msr(D) in N. subflava was likely derived from the macrolide efflux genetic assembly (MEGA) element in Streptococcus pneumoniae, with whom it shared 100% sequence homology ( de Block et al, 2021 ). As already described in other species, we found that the presence of the msr(D) gene in N. subflava was associated with higher azithromycin MICs ( Iannelli et al, 2018 ; Fox et al, 2021 ).…”

Antibiotic Resistance of Streptococcus pneumoniae in the Nasopharynx of Healthy Children Less than Five Years Old after the Generalization of Pneumococcal Vaccination in Marrakesh, Morocco

“…Erythromycin belongs to the macrolides class of drugs and is classified as an alternative to penicillin for the treatment of pneumococcal diseases [ 21 ]. The main mechanism of resistance to macrolides in S. pneumoniae is due to ribosomal methylation, mediated by erm(B) [ 22 ] or efflux pumps by mef(E)/mel(msr(D)) [ 23 ]. Erythromycin resistance has been recorded as the most prevalent form of antibiotic resistance around the world in recent years [ 22 ].…”

The mef (A)/ msr (D)-carrying streptococcal prophage Φ1207.3 encodes an SOS-like system, induced by UV-C light, responsible for increased survival and increased mutation rate

“…This genomic island is capable of growth phase-dependent excision and functions as a switch for the hyper mutator phenotype (67). Prophage Φ1207.3, originally found in a clinical isolate of S. pyogenes, carries the erythromycin resistance genes mef(A)-msr(D) (18)(19)(20)(21) and is able to transfer among S. pyogenes strains with different genetic background (unpublished data) and other streptococcal species such as S. gordonii and S. pneumoniae (18). Further more, genomic analysis showed that DNA segments with homology to the Φ1207.3 SOS cassette are present in different streptococci and are carried on mobile genetic elements, which have the potential to spread the cassette.…”