Staphylococcal methicillin resistance: fine focus on folds and functions

Mallorqui-Fernandez, G.; Marrero, Aniebrys; García‐Piquè, Sonia; García‐Castellanos, Raquel; Gomis‐Rüth, F. Xavier

doi:10.1016/j.femsle.2004.04.035

Cited by 6 publications

(3 citation statements)

References 51 publications

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“…46% vs. 29% prevalence, respectively). Since all isolates were oxacillin resistant, mecA -positive ( mecA encodes the penicillin binding protein 2a, the molecular determinant for methicillin resistance [21]), nuc- and femA- positive, they were confirmed as MRSA. Prior to use, the CHROMagar batch passed quality control screening with known MRSA and MSSA strains; yet only 26 isolates grew mauve colonies (which is indicative of MRSA); the use CHROMagar in this setting may need further investigations.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda

et al. 2011

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BackgroundThere is limited data on Methicillin resistant Staphylococcus aureus (MRSA) in Uganda where, as in most low income countries, the routine use of chromogenic agar for MRSA detection is not affordable. We aimed to determine MRSA prevalence among patients, healthcare workers (HCW) and the environment in the burns units at Mulago hospital, and compare the performance of CHROMagar with oxacillin for detection of MRSA.ResultsOne hundred samples (from 25 patients; 36 HCW; and 39 from the environment, one sample per person/item) were cultured for the isolation of Staphylococcus aureus. Forty one S. aureus isolates were recovered from 13 patients, 13 HCW and 15 from the environment, all of which were oxacillin resistant and mecA/femA/nuc-positive. MRSA prevalence was 46% (41/89) among patients, HCW and the environment, and 100% (41/41) among the isolates. For CHROMagar, MRSA prevalence was 29% (26/89) among patients, HCW and the environment, and 63% (26/41) among the isolates. There was high prevalence of multidrug resistant isolates, which concomitantly possessed virulence and antimicrobial resistance determinants, notably biofilms, hemolysins, toxin and ica genes. One isolate positive for all determinants possessed the bhp homologue which encodes the biofilm associated protein (BAP), a rare finding in human isolates. SCCmec type I was the most common at 54% prevalence (22/41), followed by SCCmec type V (15%, 6/41) and SCCmec type IV (7%, 3/41). SCCmec types II and III were not detected and 10 isolates (24%) were non-typeable.ConclusionsHyper-virulent methicillin resistant Staphylococcus aureus is prevalent in the burns unit of Mulago hospital.

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Section: Discussionmentioning

confidence: 99%

High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda

et al. 2011

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“…the minimum inhibitory concentration, MIC, for the strain) [16], [17]. Finally, the existence of other unknown determinants involved in mecA regulation, for instance mediating the signal transduction between the activated MecR1 and the promoter bound MecI, has been postulated based on contradictory experimental observations [13], [15], [18] and critical structural data analysis [19], [20]. Early studies on the β-lactamase regulon in S. aureus by Cohen and Sweeney have also suggested the existence of the blaR2 locus, unlinked to blaI-blaR1 and able to mediate the constitutive expression of blaZ [21].…”

Section: Introductionmentioning

confidence: 99%

Methicillin-Resistance in Staphylococcus aureus Is Not Affected by the Overexpression in Trans of the mecA Gene Repressor: A Surprising Observation

Oliveira

Lencastre²

2011

PLoS ONE

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Methicillin-resistant Staphylococcus aureus (MRSA) is intrinsically cross-resistant to virtually all β-lactam antibiotics. The central determinant for the MRSA phenotype is the mecA gene, whose transcriptional control may be mediated by a repressor (mecI) and a sensor/inducer (mecR1). The mecI-mecR1-mediated induction of mecA takes several hours rendering the strains phenotypically susceptible in spite of the presence of the resistance gene. Therefore, it has been proposed that the full resistance to β-lactams observed in many contemporary clinical MRSA strains requires a non-functional mecI-mecR1 regulatory system. The mecA gene is embedded in a large chromosomal cassette (the SCCmec element) for which several structural types have been described. Some epidemic MRSA clones, typically expressing full β-lactam resistance, carry SCCmec elements that contain an intact mecI-mecR1 locus (e.g. SCCmec types II and III). We have addressed this apparent contradiction by first sequencing the mecI coding region and mecA promoter sequences in a collection of prototype MRSA strains characterized by different SCCmec types. A conserved non-sense mutation within mecI was detected in all SCCmec type III strains tested, presumably responsible for a non-functional truncated MecI protein and, therefore, explaining the full resistance phenotype. In SCCmec type II strains no conserved mutations were found. We next transformed a collection of prototype MRSA epidemic strains with a recombinant plasmid overexpressing a wild-type copy of mecI. Surprisingly, for the great majority of the strains no significant alterations in the phenotypic expression of β-lactam resistance could be detected. These findings were confirmed and further explored, challenging the currently accepted mechanism of mecA transcriptional control. Our observations suggest the existence of yet unidentified additional determinants involved in the transcriptional control of mecA gene and point to a revision of the mecA regulatory mechanism in contemporary MRSA strains.

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“…Yet another class of aminoacyl‐tRNA‐protein transferases includes the bacterial low‐affinity penicillin‐binding proteins, also known as methicillin resistance proteins. These enzymes use aminoacyl‐tRNA cofactor, typically charged with Gly or Ala, to form interchain peptide linkers and to attach them to L ‐lysine in the linear pentapeptide‐disaccharide chains of peptidoglycan (Mallorqui‐Fernandez et al , 2004). Crystal structures of several enzymes of this family, including FemA from Staphylococcus aureus and FemX from Weissella viridescens , have been determined (Benson et al , 2002; Biarrotte‐Sorin et al , 2004).…”

Section: Introductionmentioning

confidence: 99%

Molecular dissection of arginyltransferases guided by similarity to bacterial peptidoglycan synthases

et al. 2006

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Post-translational protein arginylation is essential for cardiovascular development and angiogenesis in mice and is mediated by arginyl-transfer RNA-protein transferases Ate1-a functionally conserved but poorly understood class of enzymes. Here, we used sequence analysis to detect the evolutionary relationship between the Ate1 family and bacterial FemABX family of aminoacyl-tRNApeptide transferases, and to predict the functionally important residues in arginyltransferases, which were then used to construct a panel of mutants for further molecular dissection of mouse Ate1. Point mutations of the residues in the predicted regions of functional importance resulted in changes in enzymatic activity, including complete inactivation of mouse Ate1; other mutations altered its substrate specificity. Our results provide the first insights into the mechanisms of Ate1-mediated arginyl transfer reaction and substrate recognition, and define a new protein superfamily called Dupli-GNAT to reflect its origin by the duplication of the GNAT acetyltransferase domain.

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Staphylococcal methicillin resistance: fine focus on folds and functions

Cited by 6 publications

References 51 publications

High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda

High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda

Methicillin-Resistance in Staphylococcus aureus Is Not Affected by the Overexpression in Trans of the mecA Gene Repressor: A Surprising Observation

Molecular dissection of arginyltransferases guided by similarity to bacterial peptidoglycan synthases

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