Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus

Sieradzki, Krzysztof; Tomasz, Alexander

doi:10.1128/jb.179.8.2557-2566.1997

Cited by 279 publications

(306 citation statements)

References 43 publications

(33 reference statements)

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“…However, high-level vancomycin resistance (MICs Ն 32 g/ml) due to this resistance mechanism is not seen among clinical isolates. Here we show that high-level, passage-induced vancomycin resistance is associated with a decrease in the growth rate and the loss of SCCmec, including mecA, observations that have also been made by others (1,31,36,41). These SCCmec deletions resulted in strains with a faster growth rate and an ability to outcompete their mecA-containing vancomycin-resistant counterparts in mixed culture competition experiments (Fig.…”

Section: Discussionmentioning

confidence: 56%

“…The loss of mecA during the passage of S. aureus to high-level vancomycin resistance has been observed previously (1,31,36,41). In order to further characterize the loss of mecA during vancomycin passage, we examined three sets of strains.…”

Section: Resultsmentioning

confidence: 99%

“…PBP 2a is not capable of cross-linking peptidoglycan containing stem peptide modified by the van genes (21,39). Although it is not universally seen, there are several observations that MRSA passaged in the presence of increasing concentrations of vancomycin has a decrease in oxacillin resistance or has a deleted mecA (1,36,41). In the study described here we investigated the genetic and fitness alterations that occurred in three MRSA strains that became oxacillin susceptible during passage to high-level vancomycin resistance in compar-ison with those of isogenic strains that retained oxacillin resistance during the same vancomycin passage experiments.…”

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confidence: 99%

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Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Noto¹,

Fox²,

Archer

2008

Antimicrob Agents Chemother

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Treatment of infections caused byStaphylococcus aureus is often confounded by the bacterium's ability to develop resistance to chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) arises through the acquisition of staphylococcal chromosomal cassette mec (SCCmec), a genomic island containing the methicillin resistance determinant, mecA. In contrast, resistance to vancomycin can result from exposure to the drug, a mechanism that is not dependent upon a gene acquisition event. Here we describe three MRSA strains that became resistant to vancomycin during passage in the presence of increasing concentrations of the drug. In each case two derivative strains were isolated, one that had lost mecA and one that retained mecA during passage. Strain 5836VR lost mecA by the site-specific chromosomal excision of SCCmec, while the other two strains (strains 3130VR and VP32) deleted portions of their SCCmec elements in a manner that appeared to involve IS431. Conversion to vancomycin resistance caused a decrease in the growth rate that was partially compensated for by the deletion of mecA. In mixed-culture competition experiments, vancomycin-resistant strains that lacked mecA readily outcompeted their mecA-containing counterparts, suggesting that the loss of mecA during conversion to vancomycin resistance was advantageous to the organism.

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Section: Discussionmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Noto¹,

Fox²,

Archer

2008

Antimicrob Agents Chemother

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“…The mechanisms responsible for synergy and antagonism are not well defined. A reduction in ␤-lactam resistance in MRSA when the MIC for glycopeptides increases and the simultaneous inhibition of different stages of cell wall synthesis have been proposed as mechanisms (21,22).…”

Section: Discussionmentioning

confidence: 99%

Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods

Huang

Chen

et al. 2016

J Clin Microbiol

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Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and ␤-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699).Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 g/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any ␤-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations (P < 0.05). The overall agreement between the MDD and checkerboard methods to detect synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 g/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests.V ancomycin and other glycopeptide antibiotics are currently the standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) (1). The emergence of MRSA with reduced vancomycin susceptibility (SA-RVS) raises concerns about the reliability of vancomycin for the treatment of MRSA (2). Resistance during treatment with daptomycin has raised similar concerns about its effectiveness for life-threatening MRSA infections (3). Low serum levels and the bacteriostatic activity of tigecycline against MRSA limit its use for the treatment of MRSA bacteremia (4).The combination of vancomycin and ␤-lactam antibiotics offers a potential option for management of MRSA infections (5). This concept is based on several in vitro and animal studies that demonstrated a synergistic effect of vancomycin-␤-lactam combinations against MRSA (6-11).The current study was designed to determine the utility of a modified disk diffusion (MDD) test to assess synergy and antagonism for combinations of vancomycin and ␤-lactam antibiotics among clinical isolates of MRSA (8, 12). The CLSI checkerboard method was used as the reference for the determination of synergy. We determined the vancomycin MIC breakpoint where synergy is most commonly observed in MRSA isolates. MATERIALS AND METHODSBacterial isolates. Fifty-nine unique clinical isolates of MRSA with vancomycin MICs of Ն0.5 g/ml were obtained from patients at the Kaohsiung Veterans General Hospital in Taiwan ...

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“…Colonies that grew in the clear zone of growth inhibition were purified on a drug free agar plate and resistance levels to carbapenems were examined by agar dilution methods. on selective agar plates containing different concentrations of each carbapenem was determined (i.e., population analysis) [15]. The results are shown as a survival curve in Fig.…”

Section: Figmentioning

confidence: 99%

Potency of Carbapenems for the Prevention of Carbapenem-Resistant Mutants of Pseudomonas aeruginosa

et al. 2006

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The potencies of the carbapenems; doripenem (DRPM), meropenem (MEPM) and imipenem (IPM) in preventing the emergence of carbapenem-resistant mutants were examined in Pseudomonas aeruginosa strains. The carbapenems predominantly selected carbapenem-resistant mutants or carbapenem mutants with reduced susceptibilities that were specifically resistant to carbapenems and had arisen as a result of the reduced level of expression of the outer membrane protein with a molecular weight of about 48,000 (OprD). The potency of carbapenems in preventing the growth of the mutants differed for DRPM, MEPM and IPM. The isolation frequency of the mutant was examined on agar plates containing each of the carbapenems at a concentration of 1/2 or 1/4 MIC of each carbapenem for that mutant. Mutants were not selected on agar containing DRPM at a frequency of greater than 10 Ϫ9 per cell per generation, whereas mutants of each strain were selected on agar containing MEPM or IPM at frequencies of 10 Ϫ7 to 10 Ϫ9 per cell per generation. The drug concentrations and the drug concentration range for the selective increase of carbapenem resistant mutants in the broth culture containing each carbapenem differed for each carbapenem. DRPM exhibited both the lowest drug concentration and the narrowest range of drug concentration for selection of the carbapenem-resistant mutants. The results shown in this report indicated that DRPM exhibited the greatest ability to prevent the emergence of the mutant.

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Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus

Cited by 279 publications

References 43 publications

Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods

Potency of Carbapenems for the Prevention of Carbapenem-Resistant Mutants of Pseudomonas aeruginosa

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