Expression and inducibility in Staphylococcus aureus of the mecA gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein

Ubukata, Kimiko; Nonoguchi, Ritsuko; Matsuhashi, Michio; Konno, Masatoshi

doi:10.1128/jb.171.5.2882-2885.1989

Cited by 223 publications

(153 citation statements)

References 18 publications

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“…1 The mainstay of treatment has been the use of systemic and localized antibiotics. However, bacteria responsible for these infections continue to evolve resistance to commonly used antibiotics (i.e., methicillin) 2 and clearance of polymicrobial infection in patients can be difficult to achieve.…”

Section: Introductionmentioning

confidence: 99%

“…The objectives of this study were to (1) characterize the ability of antibiotic-loaded absorbable, synthetic, high-purity calcium sulfate (Stimulan Rapid Cure, Biocomposites, Keele, U.K.) beads to clear bacteria in liquid and plate cultures of gram-negative and grampositive cultures, (2) to compare the elution of antibiotics from calcium sulfate against PMMA (Simplex P, Stryker, Kalamazoo, MI) using the disc diffusion assay method for antimicrobial susceptibility testing, and (3) examine the structural differences between how these materials bind antibiotics as this will impact their ability to elute the drug after implantation.…”

Section: Introductionmentioning

confidence: 99%

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Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

McConoughey

Howlin

Wiseman

et al. 2014

J. Biomed. Mater. Res.

107

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Antibiotic-loaded bone cement is a primary option for treatment of orthopedic infections. Poly(methyl methacrylate) (PMMA) is a widely used cement that, when loaded with antibiotics in spacer or bead form, has been shown to reduce infection rates. However, PMMA is not resorbable and requires a second surgery for removal, while also acting as a potential foreign body for bacterial colonization. Alternatively, resorbable bone cements, such as calcium sulfate, have been proposed and present the advantage of being completely reabsorbed. It is unknown whether the antibiotic elution characteristics of absorbable bone cements are similar to PMMA. This study (1) characterized antibiotic elution from synthetic, highly purified calcium sulfate cement beads of varying sizes against pathogenic bacteria both in liquid culture and seeded on agar plates, (2) tested calcium sulfate beads against PMMA beads loaded with the same antibiotics, and (3) analyzed the structural differences between how PMMA and calcium sulfate bind to antibiotics. In every assay, the calcium sulfate beads performed as well as, or better than, the PMMA beads in inhibition of bacterial growth and elution of vancomycin in vitro with complete elution observed from calcium sulfate within three days. These data suggest that calcium sulfate, functions, as well as PMMA in the patient setting for infection control.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

McConoughey

Howlin

Wiseman

et al. 2014

J. Biomed. Mater. Res.

107

View full text Add to dashboard Cite

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“…As a result, the transpeptidase activity of PBP2a is functional at normally inhibitory concentrations of beta-lactam antibiotics, allowing cell wall synthesis to occur (2)(3)(4). Recently, a novel variant of mecA was identified in Staphylococcus aureus from cattle (5), humans, and a range of other animal species (6) in Denmark, France, The Netherlands, Ireland, Germany, Belgium, and the United Kingdom (5,(7)(8)(9)(10)(11).…”

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confidence: 99%

A Staphylococcus xylosus Isolate with a New mecC Allotype

Harrison

Paterson

Holden

et al. 2013

Antimicrob Agents Chemother

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jRecently, a novel variant of mecA known as mecC (mecA LGA251 ) was identified in Staphylococcus aureus isolates from both humans and animals. In this study, we identified a Staphylococcus xylosus isolate that harbors a new allotype of the mecC gene, mecC1. Whole-genome sequencing revealed that mecC1 forms part of a class E mec complex (mecI-mecR1-mecC1-blaZ) located at the orfX locus as part of a likely staphylococcal cassette chromosome mec element (SCCmec) remnant, which also contains a number of other genes present on the type XI SCCmec. Methicillin resistance in staphylococci is encoded by mecA, encoding the penicillin-binding protein 2a (PBP2a), which has a low affinity for beta-lactam antibiotics (1). As a result, the transpeptidase activity of PBP2a is functional at normally inhibitory concentrations of beta-lactam antibiotics, allowing cell wall synthesis to occur (2-4). Recently, a novel variant of mecA was identified in Staphylococcus aureus from cattle (5), humans, and a range of other animal species (6) in Denmark, France, The Netherlands, Ireland, Germany, Belgium, and the United Kingdom (5, 7-11). This subtype was originally designated mecA LGA251 but has since been renamed mecC and shares 70% nucleotide identity with the conventional mecA gene. The mecC gene is present with its cognate regulators mecI-mecR1, as part of a class E mec complex that shares structural similarity (mecI-mecR1-mecC-blaZ) with a mec gene complex found in Macrococcus caseolyticus (12). The class E complex is present as part of a larger, 29.4-kb, type XI staphylococcal cassette chromosome mec element (SCCmec) inserted at orfX; this element also includes the recombinase genes ccrAB and arsenic resistance genes. In this work, we describe a highly related mecC homolog present in the orfX locus in a Staphylococcus xylosus.A search of the EMBL nucleotide database identified submission of sequences from S. xylosus strain S04009 (13) with a high degree of similarity (Ͼ90%) to mecC (5, 8). However, antimicrobial susceptibility testing of strain S04009 by disk diffusion with oxacillin and cefoxitin showed it to be susceptible to both antibiotics but resistant to penicillin using British Society for Antimicrobial Chemotherapy (BSAC) criteria (version 10.2) (data not shown). Therefore, we submitted the mecC-positive strain S04009 and a mecC-negative S. xylosus isolate, S040010, for whole-genome sequencing to further characterize the mecC-containing region. Illumina library preparation was carried out as described by Quail et al. (14), and HiSeq sequencing was carried out following the manufacturer's standard protocols (Illumina, Inc.). Genome sequencing confirmed the presence of a mecC homolog in S04009 located downstream of the S. xylosus orfX homolog, a region associated with horizontally transferred elements (Fig. 1). Immediately downstream of orfX in S04009 is a 3.3-kb region that shows a high degree of similarity (Ͼ95% nucleotide identity) to the 3= end of the arginine catabolic mobile element (ACME) in the S. aureus USA300 strai...

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“…It has been established that the production of an additional penicillin-binding protein PBP-2' (PBP-2a), with low-affinity for betalactam antibiotics, is mainly involved in the mechanism of methicillin resistance of S. aureus [3]. While the PBP-2', which is encoded by a chromosomal structural gene designated as mecA, is usually induced by beta-lactam antibiotics, it is known to be constitutively produced in some MRSA [4,5]. Further epidemiological studies revealed that mecA genes are also distributed widely among CNS, and are associated with methicillin-resistance [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Detection ofmecA, femA, andfemBgenes in clinical strains of staphylococci using polymerase chain reaction

et al. 1994

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SUMMARYMecA, a structural gene located on the chromosome of Staphylococcus aureus, characterizes methicillin-resistant S. aureus (MRSA), and femA and femB(fem) genes encode proteins which influence the level of methicillin resistance of S. aureus. In order to examine effectiveness of detecting mecA and fem genes in identification of MRSA, the presence of these genes in 237 clinically isolated strains of staphylococci was investigated by polymerase chain reaction (PCR). An amplified mecA DNA fragment of 533 base pairs (bp) was detected in 100 % of oxacillin-resistant S. aureus, in 16'7 % of oxacillin-sensitive S. aureus, in 81-5 % of S. epidermidis, and in 58'3 % of other coagulase-negative staphylococci (CNS). While the PCR product of femA (509 bp) or femB (651 bp) was obtained from almost all the S. aureus strains except for five oxacillin-resistant strains (2'5%), neither of these genes were detected in CNS. Therefore, the detection offemA and femB together with mecA by PCR was considered to be a more reliable indicator to identify MRSA by differentiating it from mecA-positive CNS than single detection of mecA.

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Expression and inducibility in Staphylococcus aureus of the mecA gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein

Cited by 223 publications

References 18 publications

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

A Staphylococcus xylosus Isolate with a New mecC Allotype

Detection ofmecA, femA, andfemBgenes in clinical strains of staphylococci using polymerase chain reaction

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