A macrolide lincosamide streptogramin b resistance determinant gene ermj cloned from b. Microarray analysis of erythromycin resistance determinants. Macrolide erythromycin, lincosamide clindamycin and streptogramin b vernamycin b. Streptococcus pneumoniae serotype 3, isolated from a penicillinallergic patient and initially susceptible to fluoroquinolones, macrolides, lincosamides, quinupristindalfopristin, and telithromycin, became resistant to all these drugs during treatment. Epidemiology of macrolide andor lincosamide resistant streptococcus pneumoniae clinical isolates with ribosomal mutations. Dna sequence analysis of a portion of an ecori fragment of the bacteroides fragilis r plasmid pbf4 has allowed us to identify the macrolide lincosamide streptogramin b resistance mlsr gene, ermf. Macrolidelincosamidestreptogramin b mls resistance in c difficile is encoded by the erm b resistance determinant, which is thought to be located on a conjugative transposon, tn5398. Original article, report by the brazilian journal of infectious diseases. Molecular mechanism of macrolidelincosamide resistance in. Health, general drug resistance in microorganisms genetic aspects microbial drug. Cloning and hybridization analysis of ermp, a macrolide lincosamide streptogramin b resistance determinant from clostridium. Roberts and others published nomenclature for macrolide and macrolidelincosamide streptogramin b resistance determinants find, read and.
Jun 06, 2007 read resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics, molecular biotechnology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Resistance to macrolides and lincosamides is increasingly reported in clinical isolates of grampositive bacteria. Tn5432mediated macrolidelincosamidestreptogramin b. Monomethylation at a2058 confers high resistance to lincosamides, but low resistance to macrolides and streptogramin b antibiotics, whereas dimethylation gives high resistance to each of the three drug types and confers what is commonly termed the mls b macrolide, lincosamide, and streptogramin b antibiotics phenotype 7, 8. Characterization of a new ermrelated macrolide resistance. Resistance to macrolide, lincosamide, streptogramin, ketolide. Macrolidelincosamidestreptogramin b resistance phenotypes and. Roberts mc1, sutcliffe j, courvalin p, jensen lb, rood j, seppala h. Phenotypic and molecular characterization of resistance to macrolides, lincosamides and type b streptogramin of clinical isolates of staphylococcus spp. The resistance profiles and mechanism of macrolide resistance were investigated in isolates of streptococcus pneumoniae 1679, staphylococcus aureus 348, coagulasenegative staphylococci cons 175, and enterococcus spp 123.
The target site modification mechanism, also called macrolide lincosamide streptogramin b mls b resistance, results in resistance to ery, cli, and streptogramin b. Genes conferring resistance to macrolide, lincosamide, and streptogramin b mls antibiotics via ribosomal modification are widespread in bacteria, including clinical isolates and mlsproducing actinomycetes. Jun 21, 2005 a lincosamide and streptogramin a l sga r resistance phenotype was observed for 17 s. Mechanisms of resistance to macrolides, lincosamides, and. Pdf the macrolidelincosamidestreptogramin b resistance. The mls resistance phenotypes constitutive resistance to macrolide lincosamide streptogramin b. Thirtytwo erythromycinnonsusceptible strains were evaluated for the possibility of clonal spreading, using pfge. Streptogramin definition of streptogramin by medical dictionary. Nomenclature for macrolide and macrolidelincosamidestreptogramin b resistance determinants by m. Roberts mc, sutcliffe j, courvalin p, jensen lb, rood j, et al. In bacteria, three different acquired macrolide, lincosamide and streptogramin b resistance mechanisms have been found. We developed an oligonucleotide microarray containing seven oligonucleotide probes oligoprobes for each of the six genes erma, ermb, ermc, erea, ereb and msra b that account for. This chapter provides an overview of plasmid classification systems and then describes the various mechanisms of plasmidmediated resistance to antibacterial agents.
No pcr product was obtained for the studied isolate. They confer cross resistance between macrolides, lincosamides and streptogramin b socalled mlsb resistance and evoke most concerns. Sep 21, 2016 streptococcus pneumoniae is a common commensal and an opportunistic pathogen. Nomenclature for macrolide and macrolidelincosamide ncbi. The msr b gene is roughly half the size of msr a, but very homologous to it. Antimicrobial susceptibility was determined using etest and agar dilution methods. Drug inactivation and active efflux are the mechanisms causing streptogramin a resistance. Complete nucleotide sequence and transcription of ermf, a. Inducible resistance to macrolides, lincosamides and streptogramin type b antibiotics. This mechanism can be constitutive, where the rrna methylase is always produced, or can be inducible, where methylase is produced only in the presence of an inducing agent. Antibiotic resistance among staphylococcus aureus is of great concern worldwide. Novel determinant confers macrolide, lincosamides, and streptogramin b resistance in rhodococcus equi article pdf available in journal of equine veterinary science 39.
Staphylococci express efflux pumps with specificity for 14 and 15 member ring macrolides and streptogramin b, but not lincosamide molecules. Pdf novel determinant confers macrolide, lincosamides. Prevalence and characterization of the mechanisms of macrolide, lincosamide, and streptogramin resistance in isolates of. Prevalence of genotypes that determine resistance of. The mechanism of resistance to macrolides, lincosamides, and streptogramins b was studied in four bacillus clausii strains that are mixed in a probiotic administered to humans for prevention of gastrointestinal side effects due to oral antibiotic chemotherapy and in three reference strains of b. Nomenclature for macrolide and macrolidelincosamide. Expression of the erm a or erm b genes causes resistance to erythromycin and inducible or constitutive resistance to clindamycin, respectively, whereas expression of the mef a gene leads to resistance to erythromycin but not clindamycin. The complete nucleotide sequence of erma, the prototype macrolide lincosamide streptogramin b resistance gene from staphylococcus aureus, has been determined. Detection of multiple macrolide and lincosamideresistant. The ermb macrolide lincosamide streptogramin b mls resistance determinant from clostridium difficile 630 contains two copies of an erm b gene, separated by a 1. Bacteria acquire resistance to one or more of these antibiotics by the acquisition of a genes or with certain mutations. Nucleotide sequence and functional map of pe194, a plasmid.
Mls b resistance is either constitutive or inducible following exposure to a macrolide. Such ermtype genes encode enzymes that mono or dimethylate residue a2058 of 23s rrna. Testing for induction of clindamycin resistance in. The genes encode methyltransferase enzymes that either mono. Health, general drug resistance in microorganisms genetic aspects microbial. Jun 05, 2007 read resistance to tetracycline, macrolidelincosamidestreptogramin, trimethoprim, and sulfonamide drug classes, molecular biotechnology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. The purpose of the study was to analyze the distribution of the mls resistance genes in community and hospitalacquired staphylococcus isolates. New gene responsible for resistance of clinical corynebacteria to macrolide, lincosamide and streptogramin b.
Erythromycin resistance in staphylococcus aureus is associated most often with the presence of an rrna methylase, whose action also affects. The ermk mrna leader sequence has a total length of 357. Transcriptional attenuation control of ermk, a macrolide. Marilyn roberts university of washington department of.
Nomenclature for macrolide and macrolidelincosamide streptogramin b antibiotic resistance determinants. Preliminary data did not show classic macrolide resistance determinants for s. Roberts, joyce sutcliffe, patrice courvalin, bogo jensen, julian rood, marilyn c. The multiplicity of mechanisms of resistance, which include ribosomal modification, efflux of the antibiotic, and drug inactivation, results in a variety of phenotypes of resistance. Out of the many families of multidrug resistance pumps, lincosamides are most commonly shunted through pumps belonging to the resistance nodulationcell division superfamily. Jundishapur journal of microbiology a low prevalence of. To date, nomenclature systems have been proposed and published for. Pdf nomenclature for macrolide and macrolidelincosamide. In general, plasmidmediated resistance to antibacterials is a result of three major mechanisms. Bacterial resistance to macrolide, lincosamide, and. Macrolide m, lincosamide l, streptogramin b s b, and ketolide k antibiotics are a structurally diverse group of antibiotics that have overlapping binding sites in the peptidyl transferase region of 23s rrna. Mechanisms of resistance to macrolides, lincosamides, and ketolides.
Homology of a transferable tetracycline resistance determinant of clostridium difficile with streptococcus enterococcus faecalis transposon tn 916. Epidemiology and antibiotic susceptibility of bacteria causing skin and soft tissue. Cloning and hybridization analysis of ermp, a macrolidelincosamide streptogramin b resistance determinant from clostridium perfringens. Characterization of macrolide resistance in grampositive. Ketolides, of which telithromycin is the first to be registered for clinical use, and quinupristindalfopristin are new compounds belonging to the macrolide lincosamide streptogramin b mlsb class of. The major pathways for the evolution of bacterial resistance plasmids are discussed. The nucleotide sequence of pe194 contains 3,728 base pairs bp, corresponding to a molecular mass of 2. Resistance to macrolides in staphylococci may be due to active efflux encoded by msra or ribosomal target modification macrolidelincosamidestreptogramin b mls b resistance. Roberts, joyce sutcliffe, patrice courvalin, lars bogo jensen, julian rood and helena seppala. Clindamycinresistant streptococcus pneumoniae volume. Resistance to type b streptogramin is mediated by two genes encoding lactonases that inactivate the type b compound, namely vgb renamed vgba 3 x 3 roberts, mc, sutcliffe, j, courvalin, p et al. By the doubledisk test, 65 strains, all carrying the erm am determinant, were assigned to the constitutive macrolide, lincosamide, and streptogramin b resistance cmls phenotype, and the remaining 20, all carrying the mef e gene, were assigned to the recently described m phenotype.
The resistance mechanisms can be desribed phenotypically and by genotype phenotypic description. Nomenclature for macrolidelincosamidestreptogramin b resistance determinants. Linkage of determinants for streptogramin a, macrolide. Nomenclature for macrolide and macrolidelincosamide streptogramin b resistance determinants. Macrolides, lincosamides, and streptogramins mls resistance genes are responsible for resistance to these antibiotics in staphylococcus infections. Roberts and joyce sutcliffe and patrice courvalin and bogo jensen and julian rood and marilyn c.
Jones me, karlowsky ja, draghi dc, thornsberry c, sahm df, nathwani d. Macrolidelincosamidestreptogramin b listed as mlsb. For mrsa isolates that were erythromycin resistant and clindamycin susceptible, inducible macrolidelincosamidestreptogramin b mlsb resistance was determined by the disk diffusion method 6. Fluoroquinolone and macrolide treatment failure in. Macrolidelincosamidestreptogramin b how is macrolide. In staphylococcus aureus, three main types of mechanisms are responsible for acquired resistance to macrolide, lincosamide and streptogramin antibiotics. The strain was screened for ermtr, ermb or mefa, and mefe determinants as described 8,9. Resistance to tetracycline, macrolidelincosamidestreptogramin. Conferred by methylation of a single adenine in the bacterial 50s ribosome that binds to erythryomycin, erm. Read resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics, molecular biotechnology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Frontiers macrolide resistance in streptococcus pneumoniae. Roberts, 1, joyce sutcliffe, 2 patrice courvalin, 3 lars bogo jensen, 4 julian rood, 5 and helena seppala 6.
The resistance gene ermjwas cloned by southern blotting of. Resistance to macrolide, lincosamide, streptogramin. These newer compounds have become important in the treatment of communityacquired pneumoniae and nontuberculosismycobacterium diseases. Prevalence of erm genes encoding macrolidelincosamide. The widespread use of macrolides is associated with increased macrolide resistance in s. The macrolidelincosamidestreptogramin b resistance. Stefan schwarz have contacted the authors of the original publication with several comments and suggestions to better harmonize the correct nomenclature of the antibiotic resistance. Macrolidelincosamidestreptogramin b mls b antibiotics, especially clindamycin, are important therapeutic agents for penicillin. Correlation of agar dilution and vitek2 system for detection.
Although they are chemically distinct antibiotics, they have a similar mode of action. Streptogramin definition of streptogramin by medical. The ketolides are macrolide derivatives that have recently become available for human therapy. We investigated antimicrobial susceptibility and the molecular mechanism involved in conferring highlevel macrolide resistance in 47 clinical isolates of moraxella nonliquefaciens from japan.
Suspected pneumococcal upper respiratory infections and pneumonia are often treated with macrolide antibiotics. Temporal trends in macrolide resistance among invasive streptococcus pneumoniae isolates and. Lowlevel lincosamide resistance suggests the presence of some. Macrolides are bacteriostatic antibiotics and inhibit protein synthesis by binding to the 50s ribosomal subunit. The respective methylases are encoded by erm genes. There are two major recognized resistance phenotypes, mlsb and m mls b resistant to macrolides, lincosamides, and streptogramin b. Surveillance studies suggest that the levels of resistance to macrolide antibiotics in s. Methicillinsusceptible staphylococcus aureus st398t571. Application of molecular genetic methods in macrolide. Mechanisms of resistance to macrolides and lincosamides. To develop a dna microarray for analysis of genes encoding resistance determinants to erythromycin and the related macrolide, lincosamide and streptogramin b mls compounds.
Distribution and expression of macrolide resistance genes in. We identified a moraxella catarrhalis strain with highlevel resistance to azithromycin mic256 mg l. Antimicrobial susceptibility and mechanisms of highlevel. This resistance is further complicated by the ability of s. Macrolides, lincosamides, streptogramins, ketolides, and oxazolidinones mlsko, though chemically distinct, share overlapping binding sites on the 50s subunit of the ribosome.
Resistance of staphylococci to macrolideslincosamides. Inducible resistance to macrolide, lincosamide, and streptogramin type b antibiotics in streptomyces spp. Nomenclature for macrolide and macrolidelincosamidestreptogramin b resistance determinants marilyn c. Update on macrolidelincosamidestreptogramin, ketolide and oxazolidinone mlsko resistance genes. Nucleotide sequence of erma, a macrolidelincosamide. Mutations in the parc and gyra and in the 23s rrna and the ribosomal protein l22 genes were detected in the resistant isolates. Phenotypic and molecular characterization of resistance to.
Expression of ermk is regulated by transcriptional attenuation, in contrast to other inducible erm genes, previously described, which are regulated translationally. Nomenclature for macrolide and macrolidelincosamidestreptogramin b resistance determinants. Practical disk diffusion method for detection of inducible. Active efflux and inactivating enzymes m and l represent two additional mechanisms of resistance that are targeted only to particular antibiotics or antibiotic classes. Differentiation of resistance phenotypes among erythromycin.
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