scholarly journals Linezolid-Resistant Staphylococcus aureus Strain 1128105, the First Known Clinical Isolate Possessing thecfrMultidrug Resistance Gene

2014 ◽  
Vol 58 (11) ◽  
pp. 6592-6598 ◽  
Author(s):  
Jeffrey B. Locke ◽  
Douglas E. Zuill ◽  
Caitlyn R. Scharn ◽  
Jennifer Deane ◽  
Daniel F. Sahm ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Resistance Gene ◽  
Ribosomal Subunit ◽  
Single Copy ◽  
Aureus Strain ◽  
23S Rrna ◽  
Surveillance Program ◽  
Rrna Gene ◽  
Multidrug Resistance Gene ◽  
Content Type

ABSTRACTThe Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribosomal subunit, including some oxazolidinones, such as linezolid (LZD). The mobilecfrgene was identified in European veterinary isolates from the late 1990s, although the earliest report of a clinicalcfr-positive strain was the 2005 Colombian methicillin-resistantStaphylococcus aureus(MRSA) isolate CM05. Here, through retrospective analysis of LZDrclinical strains from a U.S. surveillance program, we identified acfr-positive MRSA isolate, 1128105, from January 2005, predating CM05 by 5 months. Molecular typing of 1128105 revealed a unique pulsed-field gel electrophoresis (PFGE) profile most similar to that of USA100,spatype t002, and multilocus sequence type 5 (ST5). In addition tocfr, LZD resistance in 1128105 is partially attributed to the presence of a single copy of the 23S rRNA gene mutation T2500A. Transformation of the ∼37-kb conjugative p1128105cfr-bearing plasmid from 1128105 intoS. aureusATCC 29213 background strains was successful in recapitulating the Cfr antibiogram, as well as resistance to aminoglycosides and trimethoprim. A 7-kbcfr-containing region of p1128105 possessed sequence nearly identical to that found in the Chinese veterinaryProteus vulgarisisolate PV-01 and in U.S. clinicalS. aureusisolate 1900, although the presence of IS431-like sequences is unique to p1128105. Thecfrgene environment in this early clinicalcfr-positive isolate has now been identified in Gram-positive and Gram-negative strains of clinical and veterinary origin and has been associated with multiple mobile elements, highlighting the versatility of this multidrug resistance gene and its potential for further dissemination.

scholarly journals Solithromycin Inhibition of Protein Synthesis and Ribosome Biogenesis in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae

2013 ◽  
Vol 57 (4) ◽  
pp. 1632-1637 ◽  
Author(s):  
Ward Rodgers ◽  
Ashley D. Frazier ◽  
W. Scott Champney
Keyword(s):  
Staphylococcus Aureus ◽  
Protein Synthesis ◽  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Ribosome Biogenesis ◽  
Antimicrobial Agents ◽  
Protein Biosynthesis ◽  
Ribosomal Subunit ◽  
23S Rrna ◽  
Content Type

ABSTRACTThe continuing increase in antibiotic-resistant microorganisms is driving the search for new antibiotic targets and improved antimicrobial agents. Ketolides are semisynthetic derivatives of macrolide antibiotics, which are effective against certain resistant organisms. Solithromycin (CEM-101) is a novel fluoroketolide with improved antimicrobial effectiveness. This compound binds to the large 50S subunit of the ribosome and inhibits protein biosynthesis. Like other ketolides, it should impair bacterial ribosomal subunit formation. This mechanism of action was examined in strains ofStreptococcus pneumoniae,Staphylococcus aureus, andHaemophilus influenzae. The mean 50% inhibitory concentrations (IC50s) for solithromycin inhibition of cell viability, protein synthesis, and growth rate were 7.5, 40, and 125 ng/ml forStreptococcus pneumoniae,Staphylococcus aureus, andHaemophilus influenzae, respectively. The net formation of the 50S subunit was reduced in all three organisms, with IC50s similar to those given above. The rates of 50S subunit formation measured by a pulse-chase labeling procedure were reduced by 75% in cells growing at the IC50of solithromycin. Turnover of 23S rRNA was stimulated by solithromycin as well. Solithromycin was found to be a particularly effective antimicrobial agent, with IC50s comparable to those of telithromycin and significantly better than those of azithromycin and clarithromycin in these three microorganisms.

scholarly journals Linezolid Surveillance Results for the United States (LEADER Surveillance Program 2014)

2016 ◽  
Vol 60 (4) ◽  
pp. 2273-2280 ◽  
Author(s):  
Robert K. Flamm ◽  
Rodrigo E. Mendes ◽  
Patricia A. Hogan ◽  
Jennifer M. Streit ◽  
James E. Ross ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Ribosomal Proteins ◽  
The United States ◽  
23S Rrna ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Content Type ◽  
Mrsa Strains ◽  
Viridans Group Streptococci

ABSTRACTThelinezolidexperience andaccuratedetermination ofresistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated wereStaphylococcus aureus(3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855),Streptococcus pneumoniae(874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (cfrandoptrA). The MIC50/90forStaphylococcus aureuswas 1/1 μg/ml, with 47.2% of isolates being methicillin-resistantStaphylococcus aureus. Linezolid was active against allStreptococcus pneumoniaestrains and beta-hemolytic streptococci with a MIC50/90of 1/1 μg/ml and against viridans group streptococci with a MIC50/90of 0.5/1 μg/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harboredcfronly (MIC, 4 μg/ml), one harbored G2576T (MIC, 8 μg/ml), and one containedcfrand G2576T with L3 changes (MIC, ≥8 μg/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of ≥4 μg/ml. Five of these were identified asStaphylococcus epidermidis, four of which containedcfrin addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (≥4 μg/ml; five with G2576T mutations, including one with an additionalcfrgene, and one strain withoptrAonly). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall.

scholarly journals Genetic Environment and Stability ofcfrin Methicillin-Resistant Staphylococcus aureus CM05

2011 ◽  
Vol 56 (1) ◽  
pp. 332-340 ◽  
Author(s):  
Jeffrey B. Locke ◽  
Shahad Rahawi ◽  
Jacqueline LaMarre ◽  
Alexander S. Mankin ◽  
Karen Joy Shaw
Keyword(s):  
Staphylococcus Aureus ◽  
Recombination Event ◽  
Sequence Similarity ◽  
Ribosomal Subunit ◽  
23S Rrna ◽  
Broad Host Range ◽  
Chromosomal Locus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Fitness Advantage

ABSTRACTThe Cfr methyltransferase confers resistance to many 50S ribosomal subunit-targeted antibiotics, including linezolid (LZD), via methylation of the 23S rRNA base A2503 in the peptidyl transferase center. Methicillin-resistantStaphylococcus aureusstrain CM05 is the first clinical isolate documented to carrycfr. Whilecfris typically plasmid borne, in CM05 it is located on the chromosome and is coexpressed withermBas part of themlroperon. Here we evaluated the chromosomal locus, association with mobile genetic elements, and stability of thecfrinsertion region in CM05. Thecfr-containingmlroperon is located within a 15.5-kb plasmid-like insertion into 23S rRNA allele 4. The region surrounding thecfrgene has a high degree of sequence similarity to the broad-host-range toxin/antitoxin multidrug resistance plasmid pSM19035, including a secondermBgene downstream of themlrlocus andistAS-istBS. Analysis of several individual CM05 colonies revealed two distinct populations for which LZD MICs were either 8 or 2 μg/ml. In the LZDscolonies (designated CM05Δ), a recombination event involving the twoermBgenes had occurred, resulting in the deletion ofcfrand the 3′ flanking region (cfr-istAS-istBS-ermB). The fitness advantage of CM05Δ over CM05 (though not likely due to thecfrdeletion itself) results in the predominance of CM05Δ in the absence of selective pressure. Minicircles resulting from theermBrecombination event and the novel association ofcfrwith the pSM19035 plasmid system support the potential for the continued dissemination ofcfr.

scholarly journals Five-Year Summary of In Vitro Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015)

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Michael A. Pfaller ◽  
Rodrigo E. Mendes ◽  
Jennifer M. Streit ◽  
Patricia A. Hogan ◽  
Robert K. Flamm
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Resistance Mechanisms ◽  
23S Rrna ◽  
Rrna Gene ◽  
Gram Positive ◽  
Content Type ◽  
Linezolid Resistance

ABSTRACT This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity in testing against Staphylococcus aureus, inhibiting >99.9% of 3,031 isolates at ≤2 µg/ml. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and 100.0% of Streptococcus pneumoniae, virdans group, and beta-hemolytic streptococcus isolates tested. The overall linezolid resistance rate remained a modest <1% from 2011 to 2015. Staphylococci, especially Staphylococcus epidermidis, showed a range of linezolid resistance mechanisms. Increased annual trends for the presence of cfr among Staphylococcus aureus isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, ≥4 µg/ml) to linezolid carried this transferrable gene (2011 to 2015). The cfr gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than S. aureus from 2011 to 2015. The optrA gene was noted in half (2/4) of the population of linezolid-nonsusceptible Enterococcus faecalis isolates from 2011 to 2015, while linezolid-nonsusceptible Enterococcus faecium isolates showed alterations predominantly (16/16) in the 23S rRNA gene (G2576T). This report confirms a long record of linezolid activity against Gram-positive isolates in the United States since regulatory approval in 2000 and reports the oxazolidinones evolving resistance mechanisms.

scholarly journals Klasterisasi Staphylococcus aureus Resisten Neutrofil Berdasar Assesory Gene Regulator

2020 ◽  
Vol 38 (2) ◽  
pp. 95
Author(s):  
Christin Marganingsih Santosa ◽  
Fajar Budi Lestari ◽  
Rini Widayanti ◽  
Siti Isrina Oktavia Salasia
Keyword(s):  
Staphylococcus Aureus ◽  
Food Poisoning ◽  
Pcr Amplification ◽  
Aureus Strain ◽  
23S Rrna ◽  
Rrna Gene ◽  
Polymorphonuclear Cells ◽  
Biochemical Tests

Staphylococcus aureus is recognized worldwide as a major pathogen causing subclinical intramammary infections in dairy cows and food poisoning due to its ability to produce enterotoxin. The study aimed to identify enterotoxins of S. aureus and clustering the enterotoxins based on assessory gene regulator (agr). Virulence of S. aureus to the host was characterized based on the response of polymorphonuclear cells to the infection. Twelve S. aureus could be isolated from milk cows in central of dairy farming in Sumedang West Java. The identification of S. aureus was based on cultural and biochemical tests and an amplification of a specific section of the 23S rRNA gene. The sensitivity test against antibiotics revealed that some isolates of S. aureus were resistant to penicillin and methycillin. By PCR amplification one or more staphylococcal enterotoxin genes could be observed five genes in combinations of sea (216 bp), seb (478 bp), seh (375 bp), sei (576 bp), and sej (142 bp). Clustering of S. aureus based on the assesory gene regulator could be grouped into 4 clusters for agr1 (1 isolat), agr2 (2 isolates), in combination for agr1 and agr2 (1 isolate), and for non agr (2 isolates). Based on the response of polymorphonuclear cell in vitro and in vivo assays, revealed that S. aureus strain I-2 (agr1 cluster) and P1 (agr1+agr2 cluster) were more resistant to polymorphonuclear cells and could survive intracellularly, indicated that these strains could be used as proper candidates to develop dignostic tool based on agr against staphylococcal mastitis.  

scholarly journals Ceftaroline Activity against Bacterial Pathogens Frequently Isolated in U.S. Medical Centers: Results from Five Years of the AWARE Surveillance Program

2015 ◽  
Vol 59 (4) ◽  
pp. 2458-2461 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Jennifer M. Streit ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Bacterial Pathogens ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Methicillin Resistant ◽  
Content Type ◽  
Medical Centers ◽  
Resistant Strains

ABSTRACTA total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. Ceftaroline inhibited allStaphylococcus aureusisolates at ≤2 μg/ml and was very active against methicillin-resistant strains (MIC at which 90% of the isolates tested are inhibited [MIC90], 1 μg/ml; 97.6% susceptible). AmongStreptococcus pneumoniaeisolates, the highest ceftaroline MIC was 0.5 μg/ml, and ceftaroline activity against the most commonEnterobacteriaceaespecies (MIC50, 0.12 μg/ml; 78.9% susceptible) was similar to that of ceftriaxone (MIC50, ≤0.25 μg/ml; 86.8% susceptible).

scholarly journals Draft Genome Sequence of Bacillus sp. Strain IGA-FME-2, Isolated from the Bulk Soil of Soybean (Glycine max L.) in Northeast China

2021 ◽  
Vol 10 (16) ◽  
Author(s):  
Zhenhua Yu ◽  
Sergio de los Santos-Villalobos ◽  
Yansheng Li ◽  
Jian Jin ◽  
Fannie Isela Parra Cota ◽  
...  
Keyword(s):  
Glycine Max ◽  
Draft Genome ◽  
Gc Content ◽  
Single Copy ◽  
Bulk Soil ◽  
23S Rrna ◽  
Protein Coding ◽  
Content Type ◽  
Protein Coding Genes ◽  
Glycine Max L

ABSTRACT Here, we present the draft genome of Bacillus sp. strain IGA-FME-2. This strain was isolated from the bulk soil of soybean (Glycine max L.). Its genome consists of 3,810 protein-coding genes, 44 tRNAs, two 16S rRNAs, and a single copy of 23S rRNA, with a GC content of 46.4%.

scholarly journals Genome Sequence of a Staphylococcus aureus Strain Isolated from a Dairy Cow That Was Nonresponsive to Antibiotic Treatment

2020 ◽  
Vol 9 (20) ◽  
Author(s):  
John D. Lippolis ◽  
Ellie J. Putz ◽  
Hao Ma ◽  
David P. Alt ◽  
Eduardo Casas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dairy Cattle ◽  
Antibiotic Treatment ◽  
Genome Sequence ◽  
Dairy Cow ◽  
Aureus Strain ◽  
Chronic Case ◽  
Content Type

Staphylococcus aureus can cause mastitis in dairy cattle. We report the genome sequence of a Staphylococcus aureus strain isolated from a dairy cow with a chronic case of mastitis. The infection with this strain of Staphylococcus aureus was not cleared from the animal with antibiotic treatment.

scholarly journals Novel Plasmid-Borne Multidrug Resistance Gene Cluster Includinglsa(E) from a Linezolid-Resistant Enterococcus faecium Isolate of Swine Origin

2015 ◽  
Vol 59 (11) ◽  
pp. 7113-7116 ◽  
Author(s):  
Hongbin Si ◽  
Wan-Jiang Zhang ◽  
Shengbo Chu ◽  
Xiu-Mei Wang ◽  
Lei Dai ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Gene Cluster ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Enterococcus Faecium ◽  
Insertion Element ◽  
Multidrug Resistance Gene ◽  
Content Type ◽  
Recombination Processes ◽  
Faecium Isolate

ABSTRACTA novel nonconjugative plasmid of 28,489 bp from a porcine linezolid-resistantEnterococcus faeciumisolate was completely sequenced. This plasmid harbored a novel type of multiresistance gene cluster that comprised the resistance geneslnu(B),lsa(E),spw,aadE,aphA3, and two copies oferm(B), which account for resistance to macrolides, lincosamides, streptogramins, pleuromutilins, streptomycin, spectinomycin, and kanamycin/neomycin. Structural comparisons suggested that this plasmid might have developed from other enterococcal plasmids by insertion element (IS)-mediated interplasmid recombination processes.

scholarly journals Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States

2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
The United States ◽  
Resistance Mechanisms ◽  
Regulatory Approval ◽  
Surveillance Program ◽  
Gram Positive ◽  
Content Type

ABSTRACTThis study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980Staphylococcus aureusisolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.

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