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Eagle-type methicillin resistance: new phenotype of high methicillin resistance under mec regulator gene control.

ABSTRACT: We report a novel phenotype of methicillin resistance, designated "Eagle-type" resistance, which is characteristic in its resistance to high concentrations of methicillin (64 to 512 microg/ml) and susceptibility to low concentrations of methicillin (2 to 16 microg/ml). The type of resistance was expressed in mutant strains selected with high concentrations (e.g., 128 to 512 microg/ml) of methicillin from the pre-methicillin-resistant Staphylococcus aureus strain N315, whose mecA gene transcription is strongly repressed by the mecI gene-encoded repressor protein MecI. The Eagle-type mutant strains harbored no mutation in the mecI gene or in the operator region of mecA gene to which MecI repressor is supposed to bind. In the representative Eagle-type strain h4, repression of mecA gene transcription and penicillin-binding protein 2' production were found to be released by exposing the cells to a high concentration (128 microg/ml) of methicillin but not to lower concentrations (1 and 8 microg/ml) of methicillin. The strain h4 expressed paradoxical susceptibility (Eagle effect) to the cytokilling activity of methicillin. Experimental deletion of mecI gene from the chromosome of h4 by mecI-specific gene substitution converted its Eagle-type resistance to homogeneously high methicillin resistance. We cloned two novel genes, designated hmrA and hmrB, from genomic library of h4, which conferred Eagle-type resistance to N315 when introduced into the cell in multiple copies. The genes were shown to confer homogeneous methicillin resistance to the heterogeneously methicillin-resistant strain LR5 when they were introduced into on multicopy plasmids. This result strongly indicated that the genetic alteration responsible for the expression of the Eagle phenotype is identical, or equivalent in its effect, to the genetic alteration underlying heterogeneous-to-homogeneous conversion of methicillin resistance in S. aureus.

SUBMITTER: Kondo N

PROVIDER: S-EPMC90380 | biostudies-literature | 2001 Mar

REPOSITORIES: biostudies-literature

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Eagle-type methicillin resistance: new phenotype of high methicillin resistance under mec regulator gene control.

Kondo N N Kuwahara-Arai K K Kuroda-Murakami H H Tateda-Suzuki E E Hiramatsu K K

Antimicrobial agents and chemotherapy 20010301 3

We report a novel phenotype of methicillin resistance, designated "Eagle-type" resistance, which is characteristic in its resistance to high concentrations of methicillin (64 to 512 microg/ml) and susceptibility to low concentrations of methicillin (2 to 16 microg/ml). The type of resistance was expressed in mutant strains selected with high concentrations (e.g., 128 to 512 microg/ml) of methicillin from the pre-methicillin-resistant Staphylococcus aureus strain N315, whose mecA gene transcripti ...[more]

PMID: 11181367

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Project description:Background and objectivesMRSA became a widely recognized cause of mortality worldwide with necessity of its epidemiological pattern study. Typing of MRSA isolates was performed molecularly based on SCCmec type and relation to resistance pattern was investigated.Materials and methodsOut of 200 clinical specimens, S. aureus was detected phenotypically and confirmed as MRSA by PCR in 124 isolates obtained from associated laboratories of different hospitals of Zagazig, during 2018-2019. Antimicrobial resistance pattern was detected and MRSA SCCmec was typed by two methods.ResultsS. aureus rate was high in wounds, sputum, blood, and urine isolates. Antimicrobial resistance rates against cefotaxime, tetracycline, gentamicin, ciprofloxacin, erythromycin, azithromycin, clindamycin, chloramphenicol, sulfamethoxazole-trimethoprim, linezolid and vancomycin were 82.3%, 65.3%, 56.4%, 45.1%, 37.1%, 32.3%, 32.3%, 25%, 7.3%, 2.4% and 0%, respectively. Multiplex-PCR(M-PCR) was able to detect SCCmec element among 57% of isolates classified as SCCmec II (n=40), III (n=21), IVa (n=3), IVd (n=2), V(n=1), and four isolates contain both SCCmec II and SCCmec IV. Traditional typing by PCR for mec and ccr gene complexes was almost concordant with M-PCR. Furthermore, it was able to identify SCCmec types VI, IX, and XIV among 1, 3 and 18 isolates, respectively. No Statistical correlation was established between type of cassette and rate of antimicrobial resistance. Phylogenetic analysis reveals that all ccr types were related to each other and no significant variation in the same ccr type of different SCCmec cassettes.ConclusionMost MRSA isolates were MDR reflecting antimicrobials misuse. Detection of various SCCmec types among MRSA isolates indictae the complexity of MRSA epidemiology and increase chance for gene sharing creating new types. The presented investigation was important in understanding MRSA epidemiology and diversity in Egypt providing advice for improving therapeutic protocols.

Dataset Information

Eagle-type methicillin resistance: new phenotype of high methicillin resistance under mec regulator gene control.

Publications

Eagle-type methicillin resistance: new phenotype of high methicillin resistance under mec regulator gene control.

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