scholarly journals Staphylococcus aureus VRSA-11B Is a Constitutive Vancomycin-Resistant Mutant of Vancomycin-Dependent VRSA-11A

2012 ◽  
Vol 56 (9) ◽  
pp. 4693-4696 ◽  
Author(s):  
Bruno Périchon ◽  
Patrice Courvalin
Keyword(s):  
Staphylococcus Aureus ◽  
Insertion Sequence ◽  
Constitutive Expression ◽  
Growth Curves ◽  
Resistant Mutant ◽  
Vancomycin Resistance ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Dipeptidase Activity

ABSTRACTVancomycin-resistantStaphylococcus aureusVRSA-10 was isolated in 2009, whereas VRSA-11A and VRSA-11B were isolated from the same patient in 2010. Growth curves and determination of the nature of the peptidoglycan precursors and of the VanXd,d-dipeptidase activity in the absence and in the presence of vancomycin indicated that vancomycin resistance was inducible in VRSA-10, that VRSA-11A was partially dependent on glycopeptide for growth, and that VRSA-11B was constitutively resistant. Both VRSA-11A and -11B harbored an insertion sequence, ISEf1, at the same locus in thevanX-vanYintergenic region of Tn1546and an S183A mutation in the chromosomald-alanyl:d-alanine ligase (Ddl). This substitution has been shown to be responsible for a drastic diminution of the affinity of the enzyme ford-Ala at subsite 1 inEscherichia coliDdlB. VRSA-11B exhibited an additional mutation, P216T, in the transcriptional regulator VanR, most probably associated with constitutive expression of vancomycin resistance. It is thus likely that VRSA-11B is a constitutive derivative of VRSA-11A selected during prolonged vancomycin therapy. Synthesis of peptidoglycan precursors ending ind-Ala-d-lactate was responsible for oxacillin susceptibility of VRSA-11A and VRSA-11B despite the presence of a wild-typemecAgene in both strains.

scholarly journals Genomic Analysis of the Emergence of Vancomycin-Resistant Staphylococcus aureus

mBio ◽  
2012 ◽  
Vol 3 (4) ◽  
Author(s):  
Scott D. Kobayashi ◽  
James M. Musser ◽  
Frank R. DeLeo
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Dna Sequences ◽  
Clonal Complex ◽  
Infectious Agent ◽  
The United States ◽  
Vancomycin Resistance ◽  
Genetic Characteristics ◽  
Content Type ◽  
Vancomycin Resistant

ABSTRACT Staphylococcus aureus is a human commensal bacterium and a prominent cause of infections globally. The high incidence of S. aureus infections is compounded by the ability of the microbe to readily acquire resistance to antibiotics. In the United States, methicillin-resistant S. aureus (MRSA) is a leading cause of morbidity and mortality by a single infectious agent. Therapeutic options for severe MRSA infections are limited to a few antibiotics to which the organism is typically susceptible, including vancomycin. Acquisition of high-level vancomycin resistance by MRSA is a major concern, but to date, there have been only 12 vancomycin-resistant S. aureus (VRSA) isolates reported in the United States and all belong to a phylogenetic lineage known as clonal complex 5. To gain enhanced understanding of the genetic characteristics conducive to the acquisition of vancomycin resistance by S. aureus , V. N. Kos et al. performed whole-genome sequencing of all 12 VRSA isolates and compared the DNA sequences to the genomes of other S. aureus strains. The findings provide new information about the evolutionary history of VRSA and identify genetic features that may bear on the relationship between S. aureus clonal complex 5 strains and the acquisition of vancomycin resistance genes from enterococci.

scholarly journals In VivoStudies Suggest that Induction of VanS-Dependent Vancomycin Resistance Requires Binding of the Drug to d-Ala-d-Ala Termini in the Peptidoglycan Cell Wall

2013 ◽  
Vol 57 (9) ◽  
pp. 4470-4480 ◽  
Author(s):  
Min Jung Kwun ◽  
Gabriela Novotna ◽  
Andrew R. Hesketh ◽  
Lionel Hill ◽  
Hee-Jeon Hong
Keyword(s):  
Cell Wall ◽  
Transcriptional Activation ◽  
Streptomyces Coelicolor ◽  
Constitutive Expression ◽  
Transcriptional Response ◽  
Vancomycin Resistance ◽  
Content Type ◽  
Expression Of Genes ◽  
Peptidoglycan Cell Wall

ABSTRACTVanRS two-component regulatory systems are key elements required for the transcriptional activation of inducible vancomycin resistance genes in bacteria, but the precise nature of the ligand signal that activates these systems has remained undefined. Using the resistance system inStreptomyces coelicoloras a model, we have undertaken a series ofin vivostudies which indicate that the VanS sensor kinase in VanB-type resistance systems is activated by vancomycin in complex with thed-alanyl-d-alanine (d-Ala-d-Ala) termini of cell wall peptidoglycan (PG) precursors. Complementation of an essentiald-Ala-d-Ala ligase activity by constitutive expression ofvanAencoding a bifunctionald-Ala-d-Ala andd-alanyl-d-lactate (d-Ala-d-Lac) ligase activity allowed construction of strains that synthesized variable amounts of PG precursors containingd-Ala-d-Ala. Assays quantifying the expression of genes under VanRS control showed that the response to vancomycin in these strains correlated with the abundance ofd-Ala-d-Ala-containing PG precursors; strains producing a lower proportion of PG precursors terminating ind-Ala-d-Ala consistently exhibited a lower response to vancomycin. Pretreatment of wild-type cells with vancomycin or teicoplanin to saturate and mask thed-Ala-d-Ala binding sites in nascent PG also blocked the transcriptional response to subsequent vancomycin exposure, and desleucyl vancomycin, a vancomycin analogue incapable of interacting withd-Ala-d-Ala residues, failed to inducevangene expression. Activation of resistance by a vancomycin–d-Ala-d-Ala PG complex predicts a limit to the proportion of PG that can be derived from precursors terminating ind-Ala-d-Lac, a restriction also enforced by the bifunctional activity of the VanA ligase.

scholarly journals Activities of Oxadiazole Antibacterials against Staphylococcus aureus and Other Gram-Positive Bacteria

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Derong Ding ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Mrsa Strains

ABSTRACT The activities of four oxadiazoles were investigated with 210 methicillin-resistant Staphylococcus aureus (MRSA) strains. MIC50 and MIC90 values of 1 to 2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA strains. The MIC for ND-421 is lowered severalfold in combination with oxacillin, as they synergize. The MIC90 of ND-421 against vancomycin-resistant enterococci is ≤1 μg/ml.

scholarly journals New Gram-Positive Agents: the Next Generation of Oxazolidinones and Lipoglycopeptides

2016 ◽  
Vol 54 (9) ◽  
pp. 2225-2232 ◽  
Author(s):  
Matthew P. Crotty ◽  
Tamara Krekel ◽  
Carey-Ann D. Burnham ◽  
David J. Ritchie
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Next Generation ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
The U.S

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibitin vitroactivity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstratein vitroactivity against VRE. These new Gram-positive agents are reviewed here.

scholarly journals Homologous Recombination within Large Chromosomal Regions Facilitates Acquisition of β-Lactam and Vancomycin Resistance in Enterococcus faecium

2016 ◽  
Vol 60 (10) ◽  
pp. 5777-5786 ◽  
Author(s):  
Mónica García-Solache ◽  
Francois Lebreton ◽  
Robert E. McLaughlin ◽  
James D. Whiteaker ◽  
Michael S. Gilmore ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Genomic Dna ◽  
Large Scale ◽  
Vancomycin Resistance ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Single Nucleotide ◽  
Content Type ◽  
Donor Chromosome ◽  
Vancomycin Resistant

ABSTRACTThe transfer of DNA betweenEnterococcus faeciumstrains has been characterized both by the movement of well-defined genetic elements and by the large-scale transfer of genomic DNA fragments. In this work, we report on the whole-genome analysis of transconjugants resulting from mating events between the vancomycin-resistantE. faeciumC68 strain and the vancomycin-susceptible D344RRF strain to discern the mechanism by which the transferred regions enter the recipient chromosome. Vancomycin-resistant transconjugants from five independent matings were analyzed by whole-genome sequencing. In all cases but one, the penicillin binding protein 5 (pbp5) gene and the Tn5382vancomycin resistance transposon were transferred together and replaced the correspondingpbp5region of D344RRF. In one instance, Tn5382inserted independently downstream of the D344RRFpbp5gene. Single nucleotide variant (SNV) analysis suggested that entry of donor DNA into the recipient chromosome occurred by recombination across regions of homology between donor and recipient chromosomes, rather than through insertion sequence-mediated transposition. The transfer of genomic DNA was also associated with the transfer of C68 plasmid pLRM23 and another putative plasmid. Our data are consistent with the initiation of transfer by cointegration of a transferable plasmid with the donor chromosome, with subsequent circularization of the plasmid-chromosome cointegrant in the donor prior to transfer. Entry into the recipient chromosome most commonly occurred across regions of homology between donor and recipient chromosomes.

scholarly journals Rapid Microarray-Based Identification of DifferentmecAAlleles in Staphylococci

2012 ◽  
Vol 56 (11) ◽  
pp. 5547-5554 ◽  
Author(s):  
Stefan Monecke ◽  
Elke Müller ◽  
Stefan Schwarz ◽  
Helmut Hotzel ◽  
Ralf Ehricht
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid Sequences ◽  
Animal Origin ◽  
Coagulase Negative Staphylococci ◽  
Content Type ◽  
Diagnostic Assays ◽  
Rapid Discrimination ◽  
Unique Amino Acid ◽  
Full Length Gene

ABSTRACTTo screen isolates and to identifymecAalleles, publishedmecAsequences were analyzed, and a microarray for the rapid discrimination ofmecAalleles was designed. A GenBank analysis yielded 135 full-length gene sequences annotated asmecA. These sequences clustered into 32 different alleles corresponding to 28 unique amino acid sequences and to 15 distinct hybridization patterns on this microarray. A collection of 78 clinical and veterinary isolates ofStaphylococcusspp. was characterized using this assay. Nine of the 15 expected patterns, as well as one as-yet-unknown pattern, were identified. These patterns were detected in various epidemic methicillin-resistantStaphylococcus aureusstrains, inS. pseudintermedius, and in coagulase-negative species such asS. epidermidis,S. fleurettii, orS. haemolyticus. There was no correlation between the differentmecAhybridization patterns and the SCCmectype. Determination of MICs showed thatmecAalleles corresponding to only four of these nine patterns were associated with β-lactam resistance. ThemecAalleles that did not confer β-lactam resistance were largely restricted to coagulase-negative staphylococci of animal origin, such asS. sciuriandS. vitulinus. Because of the diversity of sequences and the different impact on β-lactam susceptibility, the existence of differentmecAalleles needs to be taken into account when designing diagnostic assays for the detection ofmecA.

Vancomycin Resistance Among Clinical Isolates of Staphylococcus aureus Obtained from Selected Hospitals in Sokoto Metropolis

2020 ◽  
pp. 111-116
Author(s):  
Umar A.I. ◽  
Keyword(s):  
Staphylococcus Aureus ◽  
Public Awareness ◽  
Vancomycin Resistance ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Major Public Health Problem ◽  
Drug Resistant ◽  
Sensitivity Testing ◽  
Vancomycin Resistant ◽  
Mic Value

The decreased vancomycin susceptibility and subsequent emergence of vancomycin resistant Staphylococcus aureus (VRSA) strains is a major public health problem. This study was aimed at detecting the prevalence of vancomycin resistant Staphylococcus aureus among clinical isolates obtained from patients attending Specialist Hospital Sokoto and Maryam Abacha Women and Children Hospital Sokoto. A total of 80 S. aureus clinical isolates were obtained from the medical microbiology laboratories of the selected hospitals. Antibiotic sensitivity testing of the isolates was carried out using the agar dilution method and isolates were screened for vancomycin resistance using vancomycin agar screen method. Of the 80 S. aureus isolates studied, 69 (86.0%) were identified as vancomycin susceptible S. aureus (VSSA) with MIC value of ≤2 µg/ml, 11 (13.8%) were identified as vancomycin intermediate S. aureus (VISA) and had MIC value of 4-8 µg/mL (VISA) and none of the isolates was identified as vancomycin resistant S. aureus (VRSA). The study detects high prevalence rate of VISA in the study area and identifies the need for increased public awareness on the danger associated with the presence of drug resistant bacteria. Emphasis should be directed at discouraging practices such as the use of over the counter medications which increase the rate of development of drug resistant organisms. Keywords: Vancomycin, Resistance, Staphylococcus aureus, MIC, VRSA

scholarly journals Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains and Their Positions within the Clade Most Commonly Associated with Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States

mBio ◽  
2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Veronica N. Kos ◽  
Christopher A. Desjardins ◽  
Allison Griggs ◽  
Gustavo Cerqueira ◽  
Andries Van Tonder ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Infection ◽  
Vancomycin Resistant ◽  
Foreign Dna ◽  
Mrsa Strains ◽  
Hospital Acquired

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistantS. aureus(VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift indprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.IMPORTANCEInvasive methicillin-resistantStaphylococcus aureus(MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistantS. aureus(VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546from enterococcal donors. All acquisitions of Tn1546so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.

scholarly journals Penicillin-Binding Protein 2 Is Essential for Expression of High-Level Vancomycin Resistance and Cell Wall Synthesis in Vancomycin- Resistant Staphylococcus aureus Carrying the Enterococcal vanA Gene Complex

2004 ◽  
Vol 48 (12) ◽  
pp. 4566-4573 ◽  
Author(s):  
Anatoly Severin ◽  
Shang Wei Wu ◽  
Keiko Tabei ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Binding Protein ◽  
Inducible Promoter ◽  
Protein Product ◽  
Vancomycin Resistance ◽  
Penicillin Binding Protein ◽  
Oxacillin Resistance ◽  
Vancomycin Resistant ◽  
High Level

ABSTRACT A combination of biochemical and genetic experiments were performed in order to better understand the mechanism of expression of high-level vancomycin resistance in Staphylococcus aureus. The transcription of pbp2 of the highly vancomycin- and oxacillin-resistant strain COLVA200 and its mutant derivative with inactivated mecA were put under the control of an inducible promoter, and the dependence of oxacillin and vancomycin resistance and cell wall composition on the concentration of the isopropyl-β-d-thiogalactopyranoside inducer was determined. The results indicate that mecA—the genetic determinant of oxacillin resistance—while essential for oxacillin resistance, is not involved with the expression of vancomycin resistance. Penicillin binding protein 2A, the protein product of mecA, appears to be unable to utilize the depsipeptide cell wall precursor produced in the vancomycin-resistant cells for transpeptidation. The key penicillin binding protein essential for vancomycin resistance and for the synthesis of the abnormally structured cell walls characteristic of vancomycin-resistant S. aureus (A. Severin, K. Tabei, F. Tenover, M. Chung, N. Clarke, and A. Tomasz, J. Biol. Chem. 279:3398-3407, 2004) is penicillin binding protein 2.

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