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Stefan Schwarz - One of the best experts on this subject based on the ideXlab platform.

  • mobile Lincosamide resistance genes in staphylococci
    Plasmid, 2018
    Co-Authors: Andrea T Fesler, Stefan Schwarz, Yang Wang
    Abstract:

    Lincosamide resistance in staphylococci is based on the expression of a number of genes which specify three major resistance mechanisms: (i) enzymatic inactivation by Lincosamide nucleotidyltransferases, (ii) ribosome protection by ABC-F proteins, and (iii) methylation of the ribosomal target sites in the 23S rRNA by Cfr or Erm methylases. So far, only two lnu genes, lnu(A) and lnu(B), which code for different types of Lincosamide nucleotidyltransferases, have been found in staphylococci. The ABC-F proteins are encoded by genes of the vga, lsa and sal classes. The corresponding proteins exhibit ATP-binding domains, but lack transmembrane regions. So far, vga(A) genes - including the variant genes vga(A)V and vga(A)LC -, vga(C) genes and vga(E) genes - including the variant gene vga(E)V -, the lsa genes lsa(B) and lsa(E), as well as the sal(A) gene have been identified in staphylococci. The aforementioned genes, except lsa(B), confer resistance not only to Lincosamides, but also to pleuromutilins and streptogramin A. The cfr and erm genes code for methylases which target the adenine residues at positions 2503 and 2048 in the 23S rRNA, respectively. While the cfr gene confers resistance to phenicols, Lincosamides, oxazolidinones, pleuromutilins and streptogramin A, the erm genes mediate resistance to macrolides, Lincosamides and streptogramin B. Many of the aforementioned Lincosamide resistance genes are located on either plasmids or transposons and as such, can easily be disseminated across strain, species, and genus boundaries. The co-location of other antimicrobial resistance genes on the same mobile genetic element facilitates co-selection and persistence of the Lincosamide resistance genes under the selective pressure imposed by other antimicrobial agents.

  • Small Antimicrobial Resistance Plasmids in Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC398
    Frontiers Media S.A., 2018
    Co-Authors: Andrea Feßler, Stefan Schwarz, Yang Wang, Jianzhong Shen, Kristina Kadlec, Wan-jiang Zhang
    Abstract:

    Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates of the clonal complex 398 are often resistant to a number of antimicrobial agents. Studies on the genetic basis of antimicrobial resistance in these bacteria identified SCCmec cassettes, various transposons and plasmids of different sizes that harbor antimicrobial resistance genes. While large plasmids that carry multiple antimicrobial resistance genes – occasionally together with heavy metal resistance genes and/or virulence genes – are frequently seen in LA-MRSA ST398, certain resistance genes are also associated with small plasmids of up to 15 kb in size. These small resistance plasmids usually carry only one, but in rare cases also two or three antimicrobial resistance genes. In the current review, we focus on small plasmids that carry the macrolide-Lincosamide-streptogramin B resistance genes erm(C) or erm(T), the Lincosamide resistance gene lnu(A), the pleuromutilin-Lincosamide-streptogramin A resistance genes vga(A) or vga(C), the spectinomycin resistance gene spd, the apramycin resistance gene apmA, or the trimethoprim resistance gene dfrK. The detailed analysis of the structure of these plasmids allows comparisons with similar plasmids found in other staphylococci and underlines in many cases an exchange of such plasmids between LA-MRSA ST398 and other staphylococci including also coagulase-negative staphylococci

  • antimicrobial resistance in corynebacterium spp arcanobacterium spp and trueperella pyogenes
    Microbiology spectrum, 2017
    Co-Authors: Andrea T Fesler, Stefan Schwarz
    Abstract:

    There is currently only limited information on the antimicrobial susceptibility and resistance of Corynebacterium spp., Arcanobacterium spp., and Trueperella pyogenes from animals. The comparability of the data is hampered by the use of different antimicrobial susceptibility testing methods and interpretive criteria. To date, standard broth microdilution methods and clinical breakpoints that are approved by the Clinical and Laboratory Standards Institute and are applicable to Corynebacterium spp., Arcanobacterium spp., and T. pyogenes are available. The lack of species-specific clinical breakpoints for the different animal species reduces the explanatory power of the data. Among the isolates of the three genera, elevated MICs for different classes of antimicrobial agents (e.g., β-lactams, macrolides, Lincosamides, tetracyclines, aminoglycosides, phenicols, sulfonamides/diaminopyrimidines, and fluoroquinolones) have been described. The most comprehensive data set is available for T. pyogenes, which also includes information about genes and mutations involved in antimicrobial resistance. In T. pyogenes isolates, the macrolide-Lincosamide-streptogramin B resistance genes erm(B) and erm(X) were identified. Tetracycline resistance in T. pyogenes was based on the resistance genes tet(W), tet(Z), and tet(33), whereas the aminoglycoside resistance genes aacC, aadA1, aadA2, aadA5, aadA24, and aadB have been described in T. pyogenes. So far, only single genes conferring either phenicol resistance (cmlA6), trimethoprim resistance (dfrB2a), or β-lactam resistance (blaP1) are known to occur in T. pyogenes isolates. Various 23S rRNA mutations, including A2058T, A2058G, and G2137C, were identified in macrolide/Lincosamide-resistant T. pyogenes.

  • identification of the novel Lincosamide resistance gene lnu e truncated by isenfa5 cfr isenfa5 insertion in streptococcus suis de novo synthesis and confirmation of functional activity in staphylococcus aureus
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: Qin Zhao, Stefan Schwarz, Jianzhong Shen, Sarah Wendlandt, Yang Wang
    Abstract:

    The novel Lincosamide resistance gene lnu(E), truncated by insertion of an ISEnfa5-cfr-ISEnfa5 segment, was identified in Streptococcus suis. The gene lnu(E) encodes a 173-amino-acid protein with ≤69.4% identity to other Lincosamide nucleotidyltransferases. The lnu(E) gene and its promoter region were de novo synthesized, and Staphylococcus aureus RN4220 carrying a shuttle vector with the cloned lnu(E) gene showed a 16-fold increase in the lincomycin MIC. Mass spectrometry experiments demonstrated that Lnu(E) catalyzed the nucleotidylation of lincomycin.

  • novel and uncommon antimicrobial resistance genes in livestock associated methicillin resistant staphylococcus aureus
    Clinical Microbiology and Infection, 2012
    Co-Authors: Kristina Kadlec, Andrea T Fesler, Tomasz Hauschild, Stefan Schwarz
    Abstract:

    Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates have been the subject of numerous studies during recent years. The characterization of such isolates has usually also included the determination of their resistance phenotypes and associated resistance genotypes. Analysis of the resistance genes present in LA-MRSA isolates has revealed a number of genes commonly found in S. aureus and coagulase-negative staphylococci of humans and animals. In addition, novel resistance genes and/or resistance genes that have been rarely detected in staphylococci so far have been encountered. These include the phenicol exporter gene fexA, the multiresistance gene cfr, the tetracycline resistance gene tet(L), the trimethoprim resistance gene dfrK, the macrolide-Lincosamide-streptogramin B resistance gene erm(T), the Lincosamide-streptogramin A-pleuromutilin resistance genes vga(C) and vga(E), and the apramycin resistance gene apmA. Most of these genes were located on multiresistance plasmids in LA-MRSA. The co-localization of these resistance genes with other resistance genes enables their co-selection and persistence. LA-MRSA can therefore act as a donor and a recipient of antimicrobial resistance genes within the Gram-positive gene pool.

Vincent Perreten - One of the best experts on this subject based on the ideXlab platform.

  • Transposon-associated Lincosamide resistance lnu(C) gene identified in Brachyspira hyodysenteriae ST83
    Veterinary microbiology, 2017
    Co-Authors: Silvio De Luca, Ana B. García-martín, Friederike Zeeh, Pamela Nicholson, Chiara Francesca Magistrali, Lorenz Rychener, Joachim Frey, Vincent Perreten
    Abstract:

    Treatment of Swine Dysentery (SD) caused by Brachyspira hyodysenteriae (B. hyodysenteriae) is carried out using antimicrobials such as macrolides, Lincosamides and pleuromutilins leading to the selection of resistant strains. Whole genome sequencing of a multidrug-resistant B. hyodysenteriae strain called BH718 belonging to sequence type (ST) 83 revealed the presence of the Lincosamide resistance gene lnu(C) on the small 1724-bp transposon MTnSag1. The strain also contains an A to T substitution at position 2058 (A2058T) in the 23S rRNA gene which is known to be associated with macrolide and Lincosamide resistance in B. hyodysenteriae. Testing of additional strains showed that those containing lnu(C) exhibited a higher minimal inhibitory concentration (MIC) of lincomycin (MIC ≥ 64 mg/L) compared to strains lacking lnu(C), even if they also harbor the A2058T mutation. Resistance to pleuromutilins could not be explained by the presence of already reported mutations in the 23S rRNA gene and in the ribosomal protein L3. This study shows that B. hyodysenteriae has the ability to acquire mobile genetic elements conferring resistance to antibiotics.

  • new macrolide Lincosamide streptogramin b resistance gene erm 48 on the novel plasmid pjw2311 in staphylococcus xylosus
    Antimicrobial Agents and Chemotherapy, 2017
    Co-Authors: Juliette Ramona Karin Wipf, Matthew C Riley, Stephen A Kania, David A Bemis, Sabrina Nathalie Andreis, Sybille Schwendener, Vincent Perreten
    Abstract:

    Whole-genome sequencing of Staphylococcus xylosus strain JW2311 from bovine mastitis milk identified the novel 49.3-kb macrolide-Lincosamide-streptogramin B (MLSB) resistance plasmid pJW2311. It contained the macrolide resistance gene mph(C), the macrolide-streptogramin B resistance gene msr(A), and the new MLSB resistance gene erm(48) and could be transformed into Staphylococcus aureus by electroporation. Functionality of erm(48) was demonstrated by cloning and expression in S. aureus.

  • the new macrolide Lincosamide streptogramin b resistance gene erm 45 is located within a genomic island in staphylococcus fleurettii
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Juliette Ramona Karin Wipf, Sybille Schwendener, Jesper Bo Nielsen, Henrik Westh, Vincent Perreten
    Abstract:

    Genome alignment of a macrolide, Lincosamide, and streptogramin B (MLSB)-resistant Staphylococcus fleurettii strain with an MLSB-susceptible S. fleurettii strain revealed a novel 11,513-bp genomic island carrying the new erythromycin resistance methylase gene erm(45). This gene was shown to confer inducible MLSB resistance when cloned into Staphylococcus aureus. The erm(45)-containing island was integrated into the housekeeping gene guaA in S. fleurettii and was able to form a circular intermediate but was not transmissible to S. aureus.

  • new transposon tn6133 in methicillin resistant staphylococcus aureus st398 contains vga e a novel streptogramin a pleuromutilin and Lincosamide resistance gene
    Antimicrobial Agents and Chemotherapy, 2011
    Co-Authors: Sybille Schwendener, Vincent Perreten
    Abstract:

    A novel streptogramin A, pleuromutilin, and Lincosamide resistance determinant, Vga(E), was identified in porcine methicillin-resistant Staphylococcus aureus (MRSA) ST398. The vga(E) gene encoded a 524-amino-acid protein belonging to the ABC transporter family. It was found on a multidrug resistance-conferring transposon, Tn6133, which was comprised of Tn554 with a stably integrated 4,787-bp DNA sequence harboring vga(E). Detection of Tn6133 in several porcine MRSA ST398 isolates and its ability to circularize suggest a potential for dissemination.

Niel Hens - One of the best experts on this subject based on the ideXlab platform.

  • european surveillance of antimicrobial consumption esac outpatient macrolide Lincosamide and streptogramin mls use in europe 1997 2009
    Journal of Antimicrobial Chemotherapy, 2011
    Co-Authors: Niels Adriaenssens, Samuel Coenen, Ann Versporten, Arno Muller, Girma Minalu, Christel Faes, Vanessa Vankerckhoven, Marc Aerts, Niel Hens
    Abstract:

    Background Data on more than a decade of outpatient macrolide, Lincosamide and streptogramin (MLS) use in Europe were collected from 33 countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), using the WHO Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) methodology. Methods For the period 1997-2009, data on outpatient use of systemic MLS aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2011) per 1000 inhabitants per day (DID). Using a classification based on mean plasma elimination half-life, macrolide use was analysed for trends over time, seasonal variation and composition. Results Total outpatient MLS use in 2009 varied by a factor of 18 between the countries with highest (11.5 DID in Greece) and lowest (0.6 DID in Sweden) use. MLS use showed high seasonal variation. Short-, intermediate- and long-acting macrolides were the most commonly used agents in 2, 25 and 5 countries, respectively (mainly erythromycin, clarithromycin and azithromycin, respectively). In Sweden, mainly Lincosamides (clindamycin) were used. Lincosamide use was observed in all countries, while substantial use of a streptogramin was only seen in France (pristinamycin). For Europe, a significant increase in outpatient MLS use was found, as well as a significant seasonal variation, which increased over time from 1997 to 2009. Relative use of long-acting macrolides and Lincosamides significantly increased over time with respect to intermediate-acting macrolides, and relative use of the latter increased with respect to short-acting macrolides. Conclusions The observed differences between European countries in the levels of MLS use and the extreme seasonal variations in their use suggest that this subgroup of antibiotics is still prescribed inappropriately in many countries.

Sybille Schwendener - One of the best experts on this subject based on the ideXlab platform.

Joyce A. Sutcliffe - One of the best experts on this subject based on the ideXlab platform.

  • Macrolide, Lincosamide, Streptogramin, Ketolide, and Oxazolidinone Resistance
    Frontiers in Antimicrobial Resistance, 2014
    Co-Authors: Marilyn C. Roberts, Joyce A. Sutcliffe
    Abstract:

    Macrolides, Lincosamides, streptogramins, ketolides, and oxazolidinones (MLSKO), though chemically distinct, share overlapping binding sites on the 50S subunit of the ribosome. Bacteria acquire resistance to one or more of these antibiotics by the acquisition of a gene(s) or with certain mutations. The ketolides are macrolide derivatives that have recently become available for human therapy. The Lincosamides are a distinct group of antibiotics that are structurally unrelated to macrolides. The streptogramin B component shares an overlapping ribosomal binding site, on the 50S ribosomal subunit, with the macrolides and Lincosamides and is impacted by erm methylation at A2058 (Escherichia coli numbering). The MLSKO antibiotics inhibit protein synthesis by binding to the 50S ribosomal subunit and blocking peptide bond formation and/or translation. The binding of 14-, 15-, and 16-membered macrolides, clindamycin, and two ketolides has been described in this chapter. The Mycobacterium erm genes are regulated at the translation step. These genes confer resistance to macrolides and Lincosamides but not to streptogramin B. Mutations associated with resistance to macrolides, ketolides, streptogramins, or oxazolidinones have been described in the chapter. However, with the addition of the newer macrolides, streptogramins, ketolides, and oxazolidinones, use of this group of antibiotics has increased, and today they are important in the treatment of a variety of infectious diseases in both community and hospital environments. Ketolide resistance in streptococci and oxazolidinone resistance in gram-positive enterococci or staphylococci are surfacing with increased therapeutic use.

  • two new mechanisms of macrolide resistance in clinical strains of streptococcus pneumoniae from eastern europe and north america
    Antimicrobial Agents and Chemotherapy, 2000
    Co-Authors: A Taitkamradt, Peter C Appelbaum, Michael R. Jacobs, Todd A Davies, Florence Depardieu, Patrice Courvalin, J W Petitpas, L Wondrack, A Walker, Joyce A. Sutcliffe
    Abstract:

    Resistance to macrolides in pneumococci is generally mediated by methylation of 23S rRNA via erm(B) methylase which can confer a macrolide (M)-, Lincosamide (L)-, and streptogramin B (SB)-resistant (MLSB) phenotype or by drug efflux via mef(A) which confers resistance to 14- and 15-membered macrolides only. We studied 20 strains with unusual ML or MSB phenotypes which did not harbor erm(B) or mef(A). The strains had been isolated from patients in Eastern Europe and North America from 1992 to 1998. These isolates were found to contain mutations in genes for either 23S rRNA or ribosomal proteins. Three strains from the United States with an ML phenotype, each representing a different clone, were characterized as having an A2059G (Escherichia coli numbering) change in three of the four 23S rRNA alleles. Susceptibility to macrolides and Lincosamides decreased as the number of alleles in isogenic strains containing A2059G increased. Sixteen MSB strains from Eastern Europe were found to contain a 3-amino-acid substitution (69GTG71 to TPS) in a highly conserved region of the ribosomal protein L4 (63KPWRQKGTGRAR74). These strains formed several distinct clonal types. The single MSB strain from Canada contained a 6-amino-acid L4 insertion (69GTGREKGTGRAR), which impacted growth rate and also conferred a 500-fold increase in MIC on the ketolide telithromycin. These macrolide resistance mechanisms from clinical isolates are similar to those recently described for laboratory-derived mutants.

  • streptococcus pneumoniae and streptococcus pyogenes resistant to macrolides but sensitive to clindamycin a common resistance pattern mediated by an efflux system
    Antimicrobial Agents and Chemotherapy, 1996
    Co-Authors: Joyce A. Sutcliffe, A Taitkamradt, L Wondrack
    Abstract:

    Macrolide-resistant Streptococcus pyogenes isolates from Finland, Australia, and the United Kingdom and, more recently, Streptococcus pneumoniae and S. pyogenes strains from the United States were shown to have an unusual resistance pattern to macrolides, Lincosamides, and streptogramin B antibiotics. This pattern, referred to as M resistance, consists of susceptibility to clindamycin and streptogramin B antibiotics but resistance to 14- and 15-membered macrolides. An evaluation of the macrolide-Lincosamide-streptogramin B resistance phenotypes among our streptococcal strains collected from 1993 to 1995 suggested that this unusual resistance pattern is not rare. Eighty-five percent (n = 66) of the S. pneumoniae and 75% (n = 28) of the S. pyogenes strains in our collection had an M phenotype. The mechanism of M resistance was not mediated by target modification, as isolated ribosomes from a pneumococcal strain bearing the M phenotype were fully sensitive to erythromycin. Further, the presence of an erm methylase was excluded with primers specific for an erm consensus sequence. However, results of studies that determined the uptake and incorporation of radiolabeled erythromycin into cells were consistent with the presence of a macrolide efflux determinant. The putative efflux determinant in streptococci seems to be distinct from the multicomponent macrolide efflux system in coagulase-negative staphylococci. The recognition of the prevalence of the M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice.