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Antibiotic Dereplication Using the Antibiotic Resistance Platform
Published on: October 17, 2019
Molecular genetics of resistance to macrolides, lincosamides and streptogramin B (MLS) in streptococci
Abstract:
Resistance to macrolides-lincosamides-streptogramin B (MLS phenotype) appears in almost all streptococcal species isolated from man. Genes coding for MLS resistance are located on plasmids and one MLS resistance transposon has been described. MLS resistance genes have also been found in a large number of plasmid-free strains. Plasmids of 17 to 20 megadaltons (Mdal) that code either for MLS or for both MLS and chloramphenicol resistance are found in streptococci of groups A, B, C, D (Streptococcus faecalis) and G. These plasmids have broad host ranges (conjugative intraspecies, interspecies and intergeneric transfer), display similar restriction enzyme patterns and share a considerable degree of homology (78 to 95%). One smaller non-conjugative MLS resistance plasmid has been isolated from Str. sanguis (4.5 Mdal). In group D (Str. faecalis, Str. faecium) streptococci, MLS resistance genes are also found on plasmids that carry other antibiotic resistance (tetracycline, chloramphenicol, high-levels of streptomycin and kanamycin). These multi-resistance plasmids are either conjugative or non-conjugative and are of various sizes and molecular species and those that have been tested have narrow host-ranges. The MLS resistance genes of one multi-resistant plasmid, isolated from a strain of Str. faecalis, are located on a transposon of 3.3 Mdal, Tn917. Hybridization studies, with MLS determinants as probes, reveal homologies among various plasmid-borne MLS resistance sequences. Elements that are thought to be chromosome-borne mediate multiple antibiotic resistance (including MLS) in streptococci of groups A, B, C, D (Str. bovis), F, G, Str. pneumoniae, Str. mitis, Str. sanguis and Str. milleri. Strains harbouring such elements contain no detectable plasmid DNA. In some of the strains these elements are conjugative; their resistance markers transfer en bloc at low frequency and display narrow host ranges. Such elements, from Str. pyogenes and Str. agalactiae, were found to translocate onto various streptococcal haemolysin-bacteriocin plasmids.
Insights
Macrolides-lincosamides-streptogramin B (MLS) resistance is common in human streptococci, found on plasmids and in plasmid-free strains. MLS resistance genes can be located on transposons and chromosome-borne elements, mediating broad or narrow host range resistance.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Macrolides-lincosamides-streptogramin B (MLS) resistance is prevalent across human-associated streptococcal species.
- Resistance determinants are found on both extrachromosomal (plasmids) and chromosomal elements.
Purpose of the Study:
- To investigate the genetic basis and dissemination of MLS resistance in various streptococcal species.
- To characterize MLS resistance plasmids and transposons in streptococci.
Main Methods:
- Plasmid analysis (size, host range, conjugation)
- DNA hybridization studies using MLS resistance determinants as probes
- Characterization of transposons and chromosome-borne elements
Main Results:
- Plasmids encoding MLS resistance (17-20 Mdal) were identified in multiple streptococcal groups (A, B, C, D, G) with broad host ranges.
- MLS resistance genes were also found on multi-resistance plasmids and a transposon (Tn917) in Group D streptococci.
- Chromosome-borne elements conferring MLS resistance were detected in plasmid-free strains of numerous streptococcal species.
Conclusions:
- MLS resistance in streptococci is mediated by diverse genetic elements, including plasmids, transposons, and chromosomal DNA.
- These elements exhibit varying host ranges and contribute to the widespread dissemination of MLS resistance in human streptococci.
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