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Stefan Schwarz - One of the best experts on this subject based on the ideXlab platform.
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mobile lincosamide resistance genes in staphylococci
Plasmid, 2018Co-Authors: Andrea T Fesler, Stefan Schwarz, Yang WangAbstract: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.
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Small Antimicrobial Resistance Plasmids in Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC398
Frontiers Media S.A., 2018Co-Authors: Andrea Feßler, Stefan Schwarz, Yang Wang, Jianzhong Shen, Kristina Kadlec, Wan-jiang ZhangAbstract: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
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antimicrobial resistance in corynebacterium spp arcanobacterium spp and trueperella pyogenes
Microbiology spectrum, 2017Co-Authors: Andrea T Fesler, Stefan SchwarzAbstract: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.
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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, 2014Co-Authors: Qin Zhao, Stefan Schwarz, Jianzhong Shen, Sarah Wendlandt, Yang WangAbstract: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.
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the cfr rrna methyltransferase confers resistance to phenicols Lincosamides oxazolidinones pleuromutilins and streptogramin a antibiotics
Antimicrobial Agents and Chemotherapy, 2006Co-Authors: Katherine S Long, Stefan Schwarz, Jacob Poehlsgaard, Corinna Kehrenberg, Birte VesterAbstract:A novel multidrug resistance phenotype mediated by the Cfr rRNA methyltransferase is observed in Staphylococcus aureus and Escherichia coli. The cfr gene has previously been identified as a phenicol and lincosamide resistance gene on plasmids isolated from Staphylococcus spp. of animal origin and recently shown to encode a methyltransferase that modifies 23S rRNA at A2503. Antimicrobial susceptibility testing shows that S. aureus and E. coli strains expressing the cfr gene exhibit elevated MICs to a number of chemically unrelated drugs. The phenotype is named PhLOPSA for resistance to the following drug classes: Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics. Each of these five drug classes contains important antimicrobial agents that are currently used in human and/or veterinary medicine. We find that binding of the PhLOPSA drugs, which bind to overlapping sites at the peptidyl transferase center that abut nucleotide A2503, is perturbed upon Cfr-mediated methylation. Decreased drug binding to Cfr-methylated ribosomes has been confirmed by footprinting analysis. No other rRNA methyltransferase is known to confer resistance to five chemically distinct classes of antimicrobials. In addition, the findings described in this study represent the first report of a gene conferring transferable resistance to pleuromutilins and oxazolidinones.
Roland Leclercq - One of the best experts on this subject based on the ideXlab platform.
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Resistance to Macrolides, Lincosamides, and Streptogramins
Antimicrobial Drug Resistance, 2017Co-Authors: Vincent Cattoir, Roland LeclercqAbstract:The structurally unrelated antimicrobials, macrolides, Lincosamides, and streptogramins are grouped into a single family, called MLS family. This classification is based on a similar, although not identical, mechanism of action. Macrolides are composed of a minimum of two amino and/or neutral sugars attached to a lactone ring of variable size [1] (Fig. 18.1). Erythromycin, produced by a strain of the actinomycete Saccharopolyspora erythraea (formerly Streptomyces erythraeus), is the first macrolide discovered in 1952. It actually corresponds to a mixture of antibiotics that includes erythromycin A, which is the active compound and has a 14-membered lactone ring with two sugars, cladinose and an amino sugar (e.g., desosamine). Other commercially available macrolides derived from erythromycin A include clarithromycin, dirithromycin, roxithromycin, as well as azithromycin that has an enlarged 15-membered ring resulting from a nitrogen insertion. Structural modifications of erythromycin A resulted in improved pharmacokinetic profiles and better tolerance, but cross-resistance between members of this class of antimicrobials was still observed. Some 16-membered ring macrolides are also available in a few countries (spiramycin, josamycin, midecamycin, and miocamycin) or for veterinary use (tylosin). The most recent class of ketolides comprises telithromycin and cethromycin (ABT-773), which are derived from clarithromycin and have two major modifications, replacement of cladinose by a keto-function and an 11-12-carbamate extension with an alkyl-aryl modification in telithromycin. The first fluoroketolide solithromycin (CEM-101), exhibiting a different side chain and a fluorine atom linked to C-2 of the lactone, shows higher in vitro activity and enhanced accumulation in macrophages as compared to telithromycin [2].
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nonsense mutations in the lsa like gene in enterococcus faecalis isolates susceptible to Lincosamides and streptogramins a
Antimicrobial Agents and Chemotherapy, 2003Co-Authors: Julia Dina, Brigitte Malbruny, Roland LeclercqAbstract:The lsa gene confers intrinsic resistance to Lincosamides and streptogramins A in Enterococcus faecalis, probably by active efflux. The lsa-like genes of two clinical isolates of E. faecalis susceptible to Lincosamides and dalfopristin contained mutations that produced premature termination codons. Revertant mutants were obtained by selection on agar plates containing clindamycin.
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distribution of genes encoding resistance to macrolides Lincosamides and streptogramins among staphylococci
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Gerard Lina, Roland Leclercq, Alain Quaglia, M E Reverdy, Francois Vandenesch, Jerome EtienneAbstract:The relative frequency of 10 determinants of resistance to macrolides, Lincosamides, and streptogramins was investigated by PCR in a series of 294 macrolide-, lincosamide-, and/or streptogramin-resistant clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci isolated in 1995 from 32 French hospitals. Resistance was mainly due to the presence of ermA or ermC genes, which were detected in 259 strains (88%), in particular those resistant to methicillin (78% of the strains). Macrolide resistance due to msrA was more prevalent in coagulase-negative staphylococci (14.6%) than in S. aureus (2.1%). Genes related to linA/linA' and conferring resistance to lincomycin were detected in one strain of S. aureus and seven strains of coagulase-negative staphylococci. Resistance to pristinamycin and quinupristin-dalfopristin was phenotypically detected in 10 strains of S. aureus and in three strains of coagulase-negative staphylococci; it was always associated with resistance to type A streptogramins encoded by vat or vatB genes and occurred in association with erm genes. The vga gene conferring decreased susceptibility to type A streptogramins was present alone in three strains of coagulase-negative staphylococci and in combination with erm genes in 10 strains of coagulase-negative staphylococci. A combination of vga-vgb-vat and ermA genes was found in a single strain of S. epidermidis.
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a new resistance gene linb conferring resistance to Lincosamides by nucleotidylation in enterococcus faecium hm1025
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Roland Leclercq, Bulent Bozdogan, Latifa Berrezouga, Mingshang Kuo, David A Yurek, Kathleen Farley, Brian J StockmanAbstract:Resistance to lincomycin and clindamycin in the clinical isolate Enterococcus faecium HM1025 is due to a ribosomal methylase encoded by an ermAM-like gene and the plasmid-mediated inactivation of these antibiotics. We have cloned and determined the nucleotide sequence of the gene responsible for the inactivation of Lincosamides, linB. This gene encodes a 267-amino-acid lincosamide nucleotidyltransferase. The enzyme catalyzes 3-(5′-adenylation) (the adenylation of the hydroxyl group in position 3 of the molecules) of lincomycin and clindamycin. Expression of linB was observed in both Escherichia coli and Staphylococcus aureus. The deduced amino acid sequence of the enzyme did not display any significant homology with staphylococcal nucleotidyltransferases encoded by linA and linA′ genes. Sequences homologous to linB were found in 14 other clinical isolates of E. faecium, indicating the spread of the resistance trait in this species.
Niel Hens - One of the best experts on this subject based on the ideXlab platform.
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european surveillance of antimicrobial consumption esac outpatient macrolide lincosamide and streptogramin mls use in europe 1997 2009
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Niels Adriaenssens, Samuel Coenen, Ann Versporten, Arno Muller, Girma Minalu, Christel Faes, Vanessa Vankerckhoven, Marc Aerts, Niel HensAbstract: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.
Freddy Haesebrouck - One of the best experts on this subject based on the ideXlab platform.
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resistance to macrolides Lincosamides streptogramins and linezolid among members of the staphylococcus sciuri group
Microbial Drug Resistance, 2006Co-Authors: Srdjan Stepanovic, L A Devriese, An Martel, Annemie Decostere, Ivana Dakic, Dragana Vukovic, Lazar Ranin, Freddy HaesebrouckAbstract:This study aimed to characterize the resistance profiles of the Staphylococcus sciuri group members to macrolides, Lincosamides, streptogramins (MLS antibiotics), and linezolid upon analysis of lar...
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cloacal lactobacillus isolates from broilers show high prevalence of resistance towards macrolide and lincosamide antibiotics
Avian Pathology, 2006Co-Authors: Katty Cauwerts, Frank Pasmans, L A Devriese, An Martel, Freddy Haesebrouck, Annemie DecostereAbstract:Eighty-seven Lactobacillus strains isolated from cloacal swabs of broiler chickens derived from 20 different farms in Belgium were identified to species level and tested for susceptibility to macrolide and lincosamide antibiotics. Five different Lactobacillus species were identified as being predominantly present in the cloacae of broilers: Lactobacillus crispatus, Lactobacillus salivarius subsp. salivarius, Lactobacillus amylovorus, Lactobacillus gallinarum and Lactobacillus reuteri. Acquired resistance prevalence to macrolides and Lincosamides was very high in the investigated lactobacilli: 89% of the strains were resistant to either or both lincosamide and macrolide class antibiotics. The vast majority of these resistant strains (96%) displayed constitutive resistance. More than one-half of the macrolide and/or lincosamide resistant strains carried an erm(B), erm(C), mef(A), lnu(A) gene or a combination of these genes. Les Souches de Lactobacillus isolees de poulets de chair montrent des prevalences el...
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characterization of in vivo acquired resistance of mycoplasma hyopneumoniae to macrolides and Lincosamides
Microbial Drug Resistance, 2005Co-Authors: Tim Stakenborg, Jo Vicca, Patrick Butaye, Dominiek Maes, Chris F Minion, J Peeters, Aart De Kruif, Freddy HaesebrouckAbstract:Macrolides and related antibiotics are used to control mycoplasma infections in the pig industry worldwide. Some porcine mycoplasmas, however, survive these treatments by acquiring resistance. The mechanism of acquired resistance to macrolides and Lincosamides was studied in more detail for Mycoplasma hyopneumoniae by comparing both the phenotype and genotype of a resistant field isolate to five susceptible isolates. The MICs were significantly higher for the resistant strain for all antibiotics tested. The MICs for the 16-membered macrolide tylosin ranged from 8 to 16 microg for the resistant strain and from 0.03 to 0.125 microg/ml for the five susceptible strains. The MICs for the 15-membered macrolides and Lincosamides were higher than 64 microg/ml for the resistant strain while only 0.06 to 0.5 microg/ml for the susceptible strains. Mycoplasma hyopneumoniae strains are intrinsically resistant to the 14-membered macrolides due to a G 2057 A transition (E. coli numbering) in their 23S rDNA. Therefore, high MICs were observed for all strains, although the MICs for the resistant strain were clearly increased. An additional, acquired A 2058 G point mutation was found in the 23S rRNA gene of the resistant strain. No differences linked to resistance were found in the ribosomal proteins L4 and L22. The present study showed that 23S rRNA mutations resulting in resistance to macrolides and Lincosamides as described in other Mycoplasma spp. also occur under field conditions in M. hyopneumoniae.
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macrolide and lincosamide resistance in the gram positive nasal and tonsillar flora of pigs
Microbial Drug Resistance, 2003Co-Authors: An Martel, L A Devriese, Annemie Decostere, V Meulenaere, Freddy HaesebrouckAbstract:Macrolide and lincosamide resistance phenotypes and the presence of the erm(A), erm(B), erm(C), and mef(A) genes were determined in 344 bacterial strains belonging to 34 species and nine genera, isolated from the tonsils and nasal cavities of 2-week- and 6-week-old piglets, derived from four different farms. These piglets had never before been treated with macrolides or Lincosamides. Macrolide and lincosamide resistance was most frequently present in Streptococcus and Enterococcus strains, of which over two-thirds were resistant. These genera were followed in decreasing order of resistance frequency by Lactobacillus, Rothia, Staphylococcus, Arcanobacterium, Actinomyces, Pediococcus strains. Only five infrequently occurring species did not show resistance. This high frequency of resistance in nontreated piglets indicates that resistant strains circulate in the herds. In streptococci, enterococci, and Lactobacillus strains, resistance was most often encoded by the erm(B) gene and in staphylococci by erm(A) or erm(C). The erm(B) gene was sporadically detected in other bacterial genera (Actinomyces, Rothia, Aerococcus, Pediococcus). The sequence of the erm(B) gene of 29 strains of 11 pigs originating from the four different farms was determined. This sequence was identical in 12 strains and only differed by 1-6 nucleotides in the other strains, indicating that exchanges of resistance genes might occur between bacterial species and genera belonging to the nasal or tonsillar flora of piglets.
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prevalence and mechanism of resistance against macrolides and Lincosamides in streptococcus suis isolates
Veterinary Microbiology, 2001Co-Authors: An Martel, L A Devriese, Annemie Decostere, Margo Baele, H Goossens, Hj Wisselink, Freddy HaesebrouckAbstract:Eighty-seven Streptococcus suis isolates recovered in 1999-2000 from diseased pigs, all from different farms, were screened for resistance against macrolide and lincosamide antibiotics by the disk diffusion and agar dilution test and a PCR assay, amplifying the ermB gene and the mefA/E gene. Seventy-one percent of the isolates showed constitutive resistance to macrolide and lincosamide antibiotics (MLS(B)-phenotype). All these isolates were positive for the ermB gene in the PCR, but negative for the mefA/E gene. For all strains minimum inhibitory concentrations (MIC) against five other antimicrobial agents were determined. All strains were susceptible to penicillin. Ninety-nine percent of the isolates were susceptible to enrofloxacin and tiamulin. Eighty-five percent of the strains were resistant to doxycycline. A 540bp fragment of the ermB genes of eight S. suis strains was sequenced and compared with ermB genes of five S. pneumoniae and five S. pyogenes strains of human origin. A 100% homology was found between these fragments in seven S. suis, one S. pneumoniae and three of the S. pyogenes isolates. This study demonstrates that resistance against macrolides, Lincosamides and streptogramin B is widespread in S. suis and mediated by ribosome methylation, encoded by the ermB gene.
Yang Wang - One of the best experts on this subject based on the ideXlab platform.
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mobile lincosamide resistance genes in staphylococci
Plasmid, 2018Co-Authors: Andrea T Fesler, Stefan Schwarz, Yang WangAbstract: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.
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Small Antimicrobial Resistance Plasmids in Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC398
Frontiers Media S.A., 2018Co-Authors: Andrea Feßler, Stefan Schwarz, Yang Wang, Jianzhong Shen, Kristina Kadlec, Wan-jiang ZhangAbstract: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
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novel lnu g gene conferring resistance to lincomycin by nucleotidylation located on tn6260 from enterococcus faecalis e531
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Xiaoqing Zhu, Xiaoming Wang, Yanhong Shang, Yushan Pan, Yang Wang, Jianzhong ShenAbstract:Objectives To identify a novel putative lincosamide resistance gene determinant in a swine Enterococcus faecalis E531 exhibiting a lincosamide resistance/macrolide susceptibility (L R M S ) phenotype and to determine its location and genetic environment. Methods The whole genomic DNA of E. faecalis E531, which tested negative for the known lincosamide nucleotidyltransferase genes, was sequenced. A putative lincosamide resistance gene determinant was cloned into an Escherichia coli - E. faecalis shuttle vector (pAM401) and transformed into E. faecalis JH2-2. The MICs were determined by the microbroth dilution method. Inactivity of lincomycin was examined by UPLC-MS/MS. Inverse PCR and primer walking were used to explore the genetic environment based on the assembled sequence. Results A novel resistance gene, designated lnu (G), which encodes a putative lincosamide nucleotidyltransferase, was found in E. faecalis E531. The deduced Lnu(G) amino acid sequence displayed 76.0% identity to Lnu(B) in Enterococcus faecium . Both E. faecalis E531 and E. faecalis JH2-2 harbouring pAM401- lnu (G) showed a 4-fold increase in the MICs of lincomycin, compared with E. faecalis JH2-2 or E. faecalis JH2-2 harbouring empty vector pAM401 only. UPLC-MS/MS demonstrated that the Lnu(G) enzyme catalysed adenylylation of lincomycin. The genetic environment analysis revealed that the lnu (G) gene was embedded into a novel putative transposon, designated Tn 6260 , which was active. Conclusions A novel lincosamide nucleotidyltransferase gene lnu (G) was identified in E. faecalis . The location of the lnu (G) gene on a mobile element Tn 6260 makes it easy to disseminate.
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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, 2014Co-Authors: Qin Zhao, Stefan Schwarz, Jianzhong Shen, Sarah Wendlandt, Yang WangAbstract: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.