Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene

Ba, Xiaoliang; Harrison, Ewan M.; Edwards, Giles; Holden, Matthew T. G.; Larsen, Anders Rhod; Petersen, Andreas; Skov, Robert; Peacock, Sharon J.; Parkhill, Julian; Paterson, Gavin K.; Holmes, Mark A.

doi:10.1093/jac/dkt418

Cited by 97 publications

(99 citation statements)

References 21 publications

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“…Some researchers in Nigeria and elsewhere have also reported absence of mecA gene as well as the gene product, PBP2a or PBP2', in phenotypic MRSA strains and have suggested the possibility of hyper-production of β-lactamase as a cause of this phenomenon (11,12). We also did not test for this in our study.…”

Section: Resultsmentioning

confidence: 61%

Non detection of mecA gene in methicillin resistant Staphylococcus aureus isolates from pigs

Nwaogaraku¹,

Smith²,

Badaki³

2019

Af J Clin Exp Micro

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Background: Methicillin resistant Staphylococcus aureus (MRSA) have become a global health problem causing infections in both humans and livestock, ranging from skin and soft tissue to life threatening blood stream infections. The mecA gene is known to confer resistance to MRSA isolates. This study investigated the carriage of mecA gene by MRSA isolates from pigs. Methods: One hundred non duplicate staphylococcal isolates recovered from blood samples of pigs in Bariga district of Lagos State at the Molecular Biology and Biotechnology unit of the Nigerian Institute of Medical Research were used in the study. S. aureus was identified by cultural characteristics, and positive catalase, coagulase and deoxyribonuclease tests. Phenotypic methicillin resistance was determined by the modified Kirby Bauer disk diffusion method and mecA gene was detected by conventional polymerase chain reaction (PCR) assay. Results: Twenty-five S. aureus were identified, of which 11 (44%) were MRSA by phenotypic method. All the isolates were mecA negative on PCR. Conclusion: The MRSA phenotype observed in the pig isolates in this study appears not to be the classical mecA mediated resistance. There may be alternative mechanisms of resistance in MRSA isolates in pigs.

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Section: Resultsmentioning

confidence: 61%

Non detection of mecA gene in methicillin resistant Staphylococcus aureus isolates from pigs

Nwaogaraku¹,

Smith²,

Badaki³

2019

Af J Clin Exp Micro

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“…However, other mechanisms may be involved in the expression of oxacillin resistance such as the production of a new methicillinase, change in the penicillin-binding protein subtypes, or increased levels of resistance to cadmium (Massidda et al, 2006;Park et al, 2013). It has been shown that mutations in the penicillin-binding proteins 1, 2, and 3 may lower their affinity for the β-lactam antibiotics (Ba et al, 2014), mediating oxacillin resistance in the absence of mecA or mecC. Other studies are necessary to investigate the oxacillin resistance mechanism in the 13 mecA-and blaZ-negative CNS isolates we found in this present study.…”

Section: Discussionmentioning

confidence: 99%

Presence of mecA-positive multidrug-resistant Staphylococcus epidermidis in bovine milk samples in Brazil

Santos

Mendonça

Reis

et al. 2016

Journal of Dairy Science

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Bacteria of the genus Staphylococcus are one of the major pathogens causing bovine mastitis. In recent decades, resistance of this genus to oxacillin (methicillin) has been a matter of concern due to the possibility of reducing the effectiveness of mastitis treatments and the transfer of resistance determinants to other bacteria. Oxacillin resistance was studied in 170 staphylococci from bovine milk samples, including 79 Staphylococcus aureus and 91 coagulase-negative staphylococci (CNS). The susceptibility profile of 10 antimicrobial agents used in veterinary practice was determined by the Etest method. In addition to the Etest, the phenotypic characterization of oxacillin resistance was tested using the cefoxitin disk diffusion test. All isolates were screened by PCR to detect the mecA gene in 2 different regions of the gene. The isolates with an oxacillin minimum inhibitory concentration ≥0.5 µg/mL or resistant to cefoxitin were identified by sequencing a 536-bp fragment of the 16S rRNA gene. This group of isolates was also evaluated for the presence of blaZ and mecC genes. Molecular analysis of the mecA gene was carried out by typing of the staphylococcal cassette chromosome mec (SCCmec). The relatedness of the mecA-positive isolates was evaluated by macrorestriction of chromosomal DNA followed by pulsed-field gel electrophoresis. With the exception of penicillin and oxacillin, 86% of the isolates showed susceptibility to cephalothin, gentamicin, erythromycin, sulfonamide, trimethoprim-sulfamethoxazole, and tetracycline. All S. aureus isolates were susceptible to oxacillin, whereas 47% (n=43) of the CNS isolates were resistant. The CNS isolates showed a higher resistance to cephalothin, erythromycin, tetracycline, and gentamicin in comparison with S. aureus. The mecA gene was only detected in 10 CNS isolates, identified as Staphylococcus epidermidis, and classified into 3 pulsotypes (A, B, and C) and 4 subtypes (A1, B1, B2, and B3). Among the isolates with an oxacillin resistance phenotype, 12 were positive for the blaZ gene, and 9 of them were mecA-positive. Two of the oxacillin-resistant isolates amplified the mecA homolog gene of Staphylococcus sciuri and none amplified mecC. Three SCCmec types, I, IV, and V, were found. Our results suggest that Staphylococcus epidermidis can be a reservoir for mecA for other Staphylococcus species. Studies investigating the molecular and phenotypic profile of antimicrobial resistance in staphylococcal species should be performed for controlling the spread of resistance and the selection of appropriate therapeutic measures.

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“…Various point mutations in PBP2 and other PBPs, often in the transpeptidase domain targeted by β-lactams, have been observed in such clinical isolates (132)(133)(134)(135). There are few data on the prevalence of such isolates, but anecdotally they appear rare and their level of resistance low compared with that of mecA MRSA.…”

Section: Non-meca Gene-mediated Methicillin Resistancementioning

confidence: 99%

Mechanisms of Methicillin Resistance in Staphylococcus aureus

Peacock

Paterson

2015

Annu. Rev. Biochem.

500

371

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Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for β-lactams. This resistance allows cell-wall biosynthesis, the target of β-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile genetic element (SCCmec), the expression of which is controlled through a proteolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.

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Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene

Cited by 97 publications

References 21 publications

Non detection of <i>mecA</i> gene in methicillin resistant <i>Staphylococcus aureus</i> isolates from pigs

Non detection of <i>mecA</i> gene in methicillin resistant <i>Staphylococcus aureus</i> isolates from pigs

Presence of mecA-positive multidrug-resistant Staphylococcus epidermidis in bovine milk samples in Brazil

Mechanisms of Methicillin Resistance in Staphylococcus aureus

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