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Pharmaceuticals (Basel, Switzerland) Jun 2010Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug... (Review)
Review
Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug resistant enterococci and methicillin-resistant Staphylococus aureus. It has been used successfully for the treatment of patients with endocarditis and bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often used for treatment of complicated infections when other therapies have failed. Linezolid resistance in Gram-positive cocci has been encountered clinically as well as in vitro, but it is still a rare phenomenon. The resistance to this antibiotic has been, until now, entirely associated with distinct nucleotide substitutions in domain V of the 23S rRNA genes. The number of mutated rRNA genes depends on the dose and duration of linezolid exposure and has been shown to influence the level of linezolid resistance. Mutations in associated ribosomal proteins also affect linezolid activity. A new phenicol and clindamycin resistance phenotype has recently been found to be caused by an RNA methyltransferase designated Cfr. This gene confers resistance to lincosamides, oxazolidinones, streptogramin A, phenicols and pleuromutilins, decrease the susceptibility of S. aureus to tylosin, to josamycin and spiramycin and thus differs from erm rRNA methylase genes. Research into new oxazolidinones with improved characteristics is ongoing. Data reported in patent applications demonstrated that some oxazolidinone derivatives, also with improved characteristics with respect to linezolid, are presently under study: at least three of them are in an advanced phase of development.
PubMed: 27713338
DOI: 10.3390/ph3071988 -
Frontiers in Microbiology 2017Increasing emergence of staphylococci resistant to pleuromutilins, lincosamides, and streptogramin A (PLS) and isolated from humans and pets is a growing public health...
Increasing emergence of staphylococci resistant to pleuromutilins, lincosamides, and streptogramin A (PLS) and isolated from humans and pets is a growing public health concern worldwide. Currently, there was only one published study regarding one of the PLS genes, (A) detected in staphylococci isolated from cat. In this study, eleven pleuromutilin-resistant staphylococci from pets and two from their owners were isolated and further characterized for their antimicrobial susceptibilities, plasmid profiles, genotypes, and genetic context of the PLS resistance genes. The gene (A) identified in 11 staphylococcal isolates was found for the first time in , and . Moreover, these 11 isolates shared the identical regions flanking the (A) gene located in the chromosomal DNA. Two isolates from a cat and its owner carried similar (A) plasmids and displayed indistinguishable PFGE patterns. A novel chromosomal multidrug resistance genomic island (MDRGI) containing 13 resistance genes, including (E), was firstly identified in . In addition, (A), (A), and (E) were for the first time identified in staphylococcal isolates originating from pet animals. The plasmids, chromosomal DNA region, and MDRGI associated with the PLS resistance genes (A), (A), (A), and (E) are present in staphylococci isolated from pets and humans and present significant challenges for the clinical management of infections by limiting therapeutic options.
PubMed: 28261187
DOI: 10.3389/fmicb.2017.00234 -
Frontiers in Microbiology 2018Livestock-associated methicillin-resistant (LA-MRSA) isolates of the clonal complex 398 are often resistant to a number of antimicrobial agents. Studies on the genetic... (Review)
Review
Livestock-associated methicillin-resistant (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 SCC 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 (C) or (T), the lincosamide resistance gene (A), the pleuromutilin-lincosamide-streptogramin A resistance genes (A) or (C), the spectinomycin resistance gene , the apramycin resistance gene , or the trimethoprim resistance gene . 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.
PubMed: 30283407
DOI: 10.3389/fmicb.2018.02063 -
Clinical Microbiology and Infection :... Aug 2012Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates have been the subject of numerous studies during recent years. The characterization... (Review)
Review
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.
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gene Pool; Genes, Bacterial; Humans; Livestock; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections
PubMed: 22509728
DOI: 10.1111/j.1469-0691.2012.03842.x -
Microbiology Spectrum Jun 2023Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) isolates ( = 178) collected in the national resistance...
Genomic Diversity of Methicillin-Resistant Staphylococcus aureus CC398 Isolates Collected from Diseased Swine in the German National Resistance Monitoring Program GE-Vet from 2007 to 2019.
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) isolates ( = 178) collected in the national resistance monitoring program GE-Vet from diseased swine in Germany from 2007 to 2019 were investigated for their genomic diversity with a focus on virulence and antimicrobial resistance (AMR) traits. Whole-genome sequencing was followed by molecular typing and sequence analysis. A minimum spanning tree based on core-genome multilocus sequence typing was constructed, and antimicrobial susceptibility testing was performed. Most isolates were assigned to nine clusters. They displayed close phylogenetic relationships but a wide molecular variety, including 13 types and 19 known and four novel types. Several toxin-encoding genes, including , , , , and , were detected. The isolates harbored a wide range of AMR properties mirroring the proportions of the classes of antimicrobial agents applied in veterinary medicine in Germany. Multiple novel or rare AMR genes were identified, including the phenicol-lincosamide-oxazolidinone-pleuromutilin-streptogramin A resistance gene , the lincosamide-pleuromutilin-streptogramin A resistance gene (C), and the novel macrolide-lincosamide-streptogramin B resistance gene (54). Many AMR genes were part of small transposons or plasmids. Clonal and geographical correlations of molecular characteristics and resistance and virulence genes were more frequently observed than temporal relations. In conclusion, this study provides insight into population dynamics of the main epidemic porcine LA-MRSA lineage in Germany over a 13-year-period. The observed comprehensive AMR and virulence properties, most likely resulting from the exchange of genetic material between bacteria, highlighted the importance of LA-MRSA surveillance to prevent further dissemination among swine husbandry facilities and entry into the human community. The LA-MRSA-CC398 lineage is known for its low host specificity and frequent multiresistance to antimicrobial agents. Colonized swine and their related surroundings represent a considerable risk of LA-MRSA-CC398 colonization or infection for occupationally exposed people through which such isolates might be further disseminated within the human community. This study provides insight into the diversity of the porcine LA-MRSA-CC398 lineage in Germany. Clonal and geographical correlations of molecular characteristics and resistance and virulence traits were detected and may be associated with the spread of specific isolates through livestock trade, human occupational exposure, or dust emission. The demonstrated genetic variability underlines the lineage's ability to horizontally acquire foreign genetic material. Thus, LA-MRSA-CC398 isolates have the potential to become even more dangerous for various host species, including humans, due to increased virulence and/or limited therapeutic options for infection control. Full-scale LA-MRSA monitoring at the farm, community, and hospital level is therefore essential.
Topics: Animals; Humans; Swine; Methicillin-Resistant Staphylococcus aureus; Phylogeny; Streptogramin A; Staphylococcal Infections; Anti-Bacterial Agents; Genomics; Lincosamides; Livestock; Pleuromutilins
PubMed: 37154741
DOI: 10.1128/spectrum.00770-23 -
International Journal of Antimicrobial... Nov 2019A lincosamide-resistant and macrolide-susceptible phenotype has not been described to date in Streptococcus pyogenes [group A streptococcus (GAS)]. The aim of this study...
A novel genomic island harbouring lsa(E) and lnu(B) genes and a defective prophage in a Streptococcus pyogenes isolate resistant to lincosamide, streptogramin A and pleuromutilin antibiotics.
A lincosamide-resistant and macrolide-susceptible phenotype has not been described to date in Streptococcus pyogenes [group A streptococcus (GAS)]. The aim of this study was to characterize a GAS isolate susceptible to macrolides but resistant to lincosamide, streptogramin A and pleuromutilin antibiotics. Antimicrobial susceptibility was tested using the microdilution broth method and the resistance phenotype was tested by D-test. The GAS2887HUB isolate was subjected to whole-genome sequencing. The isolate showed a positive Gots' test (clindamycin inactivation). Whole-genome sequencing revealed that the strain was ST10 and emm93, and had five resistance genes [lnu(B), ant(6)-Ia, aph(3')-III, tet(M) and dfrG]. The tet(M) gene was located in a Tn916-like transposon. The lsa(E)-lnu(B)-containing sequence (inserted downstream of the rumA gene) was formed by a 39.6-kb prophage, followed by a gene cluster encoding aminoglycoside-streptothricin resistance [ant(6)Ia-sat4-aph(3')III] and lsa(E)-lnu(B) genes. This structure was not transferred by conjugation. This study identified a new genetic element carrying a determinant of lincosamide resistance in a GAS. Further molecular epidemiological surveys are needed to determine the prevalence of this mechanism of resistance in GAS.
Topics: Anti-Bacterial Agents; DNA, Bacterial; Defective Viruses; Diterpenes; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Genomic Islands; Humans; Lincosamides; Microbial Sensitivity Tests; Polycyclic Compounds; Prophages; Streptococcus pyogenes; Streptogramin A; Whole Genome Sequencing; Pleuromutilins
PubMed: 31476434
DOI: 10.1016/j.ijantimicag.2019.08.019 -
Clinical Microbiology Reviews Jun 2021Seven mobile oxazolidinone resistance genes, including , (B), (C), (D), (E), , and , have been identified to date. The genes code for 23S rRNA methylases, which confer...
Seven mobile oxazolidinone resistance genes, including , (B), (C), (D), (E), , and , have been identified to date. The genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The and genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The gene confers resistance to oxazolidinones and phenicols, while the gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the , , and genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on -, -, or -carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Genes, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Oxazolidinones
PubMed: 34076490
DOI: 10.1128/CMR.00188-20 -
Antimicrobial Agents and Chemotherapy Jun 2014Natural resistance to lincosamides and streptogramins A (LSA), which is a species characteristic of Bacillus subtilis and Enterococcus faecalis, has never been...
Natural resistance to lincosamides and streptogramins A (LSA), which is a species characteristic of Bacillus subtilis and Enterococcus faecalis, has never been documented in the Staphylococcus genus. We investigate here the molecular basis of the LSA phenotype exhibited by seven reference strains of Staphylococcus sciuri, including the type strains of the three described subspecies. By whole-genome sequencing of strain ATCC 29059, we identified a candidate gene that encodes an ATP-binding cassette protein similar to the Lsa and VmlR resistance determinants. Isolation and reverse transcription-quantitative PCR (qRT-PCR) expression studies confirmed that Sal(A) can confer a moderate resistance to lincosamides (8 times the MIC of lincomycin) and a high-level resistance to streptogramins A (64 times the MIC of pristinamycin II). The chromosomal location of sal(A) between two housekeeping genes of the staphylococcal core genome supports the gene's ancient origins and thus innate resistance to these antimicrobials within S. sciuri subspecies.
Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; Chromosome Mapping; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Lincosamides; Microbial Sensitivity Tests; Molecular Sequence Data; Phenotype; Phylogeny; Sequence Alignment; Sequence Analysis, DNA; Staphylococcal Infections; Staphylococcus; Streptogramin A
PubMed: 24687494
DOI: 10.1128/AAC.02797-13 -
Antimicrobial Agents and Chemotherapy Aug 2002We characterized a new transposon, Tn5406 (5,467 bp), in a clinical isolate of Staphylococcus aureus (BM3327). It carries a variant of vgaA, which encodes a putative ABC...
We characterized a new transposon, Tn5406 (5,467 bp), in a clinical isolate of Staphylococcus aureus (BM3327). It carries a variant of vgaA, which encodes a putative ABC protein conferring resistance to streptogramin A but not to mixtures of streptogramins A and B. It also carries three putative genes, the products of which exhibit significant similarities (61 to 73% amino acid identity) to the three transposases of the staphylococcal transposon Tn554. Like Tn554, Tn5406 failed to generate target repeats. In BM3327, the single copy of Tn5406 was inserted into the chromosomal att554 site, which is the preferential insertion site of Tn554. In three other independent S. aureus clinical isolates, Tn5406 was either present as a single plasmid copy (BM3318), as two chromosomal copies (BM3252), or both in the chromosome and on a plasmid (BM3385). The Tn5406-carrying plasmids also contain two other genes, vgaB and vatB. The insertion sites of Tn5406 in BM3252 were studied: one copy was in att554, and one copy was in the additional SCCmec element. Amplification experiments revealed circular forms of Tn5406, indicating that this transposon might be active. To our knowledge, a transposon conferring resistance to streptogramin A and related compounds has not been previously described.
Topics: Anti-Bacterial Agents; Chromosomes, Bacterial; Cloning, Molecular; Culture Media; DNA Transposable Elements; DNA, Bacterial; Genes, Bacterial; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Reverse Transcriptase Polymerase Chain Reaction; Staphylococcus aureus; Streptogramin A; Virginiamycin
PubMed: 12121902
DOI: 10.1128/AAC.46.8.2337-2343.2002 -
Journal of Global Antimicrobial... Dec 2023Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is an important zoonotic microorganism that increasingly causes public health concern...
OBJECTIVES
Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is an important zoonotic microorganism that increasingly causes public health concern worldwide. The objective of this study was to determine the prevalence and transmission of S. aureus in duck farms and evaluate its antimicrobial resistance and genetic characteristics.
METHODS
The samples associated with ducks, feeders, and the environment were collected on 14 duck farms from four areas in Guangdong, China, from 2020 to 2021. All isolates were subjected to antimicrobial susceptibility testing. A comprehensive epidemiological survey of S. aureus was conducted by S. aureus protein A typing and whole-genome sequencing.
RESULTS
A total of 560 samples were collected. The prevalence rate of MRSA among ducks (8.1%, 11 of 135) was higher compared with that in environmental samples. OptrA-positive ST398-t034 MRSA were first detected from duck farms in China. A total of 79.3% (34 of 46) S. aureus isolates showed multidrug-resistant phenotypes. Notably, some isolates carried multidrug-resistant genes encoding macrolide-lincosamide-streptogramin B, pleuromutilin-pleuromutilin-streptogramin A, and oxazolidinone. Analysis of the virulence genes revealed that the MRSA isolates carried genes encoding gamma-hemolysin, enterotoxin, and leukocidin. ST9-t899 is a primary clonal lineage among duck- and environment-associated MRSA. Single-nucleotide polymorphism analysis showed the potential contamination relationship of optrA-positive ST2308 MRSA isolates carrying the gamma-hemolysin genes and the leukocidin virulence genes between airborne dust and sick ducks.
CONCLUSION
The contamination of MRSA, especially optrA-positive MRSA, between food animals and the environment is a growing public health concern worldwide. Based on One Health principles, continuous surveillance of MRSA is urgently needed.
Topics: Animals; Methicillin-Resistant Staphylococcus aureus; Staphylococcus aureus; Ducks; Farms; Leukocidins; Hemolysin Proteins; Microbial Sensitivity Tests; Anti-Bacterial Agents; Pleuromutilins
PubMed: 37689309
DOI: 10.1016/j.jgar.2023.08.015