Characterization of <i>ermA</i> in Macrolide-Susceptible Strains of Methicillin-Resistant <i>Staphylococcus aureus</i>
Bibliographic record
Abstract
Two gene classes are responsible for macrolide resistance in Staphylococcus aureus. The erythromycin ribosome methylase (erm) genes confer resistance to macrolide, lincosamide, and streptogramin B antibiotics (MLSB phenotype), while the macrolide streptogramin resistance (msr) drug efflux mechanism yields an MSB phenotype (2-4). In methicillin-resistant S. aureus (MRSA), ermA resides on Tn554, located in staphylococcal cassette chromosome mec (SCCmec) types II and III (1). The Canadian Nosocomial Infection Surveillance Program (CNISP) has been characterizing MRSA isolates collected from 49 sentinel Canadian hospitals since 1995 (9). We recently identified two isolates that carried ermA yet were susceptible to erythromycin and clindamycin while characterizing the macrolide and lincosamide resistance mechanisms in a subset of CNISP isolates (5). A retrospective examination of the susceptibility and molecular typing data between 1995 and 2007 was performed to identify any additional isolates with these characteristics. A total of 13 SCCmec II MRSA isolates were found that were susceptible to erythromycin and clindamycin (MICs of 0.25 and 0.5 μg/ml, respectively). These isolates, belonging to CMRSA2 (USA100) and spa type 2 (TJMBMDMGMK), were identified from three provinces: British Columbia (2007 [n = 1]), Manitoba (2007 [n = 4]), and Ontario (2004 [n = 2], 2005 [n = 1], and 2007 [n = 5]). The presence of the ermA coding sequence was confirmed by PCR (data not shown) (8). However, amplification with primers that span a 196-bp region upstream of the translation initiation site and the entire coding sequence yielded a smaller amplicon from both genomic DNA and reverse-transcribed cDNA (data not shown). DNA sequence analysis revealed that 48 bp (nucleotides 5,277 to 5,324) of Tn554 (GenBank accession no. {type:entrez-nucleotide,attrs:{text:X03216,term_id:43726,term_text:X03216}}X03216) were missing in these isolates (Fig. (Fig.11). FIG. 1. Secondary structure of ermA mRNA permissible for translation. The region spanning positions 5,399 to 5,262 of Tn554 encodes a 19-mer peptide and IR1 to IR4 (arrows). Sequestration of IR1 by macrolide-bound ribosomes (conjoined ovals) leads to IR2:IR3 ... The translation attenuation for ermA parallels that for ermC (10). The ermA attenuation sequence is composed of at least a 19-mer peptide coding sequence and two pairs of inverted repeats (IR1 and -2 and IR3 and -4) located immediately upstream of the AUG start codon for ErmA. In the absence of inducers, ermA mRNA forms two stable hairpin structures (IR1:IR2 and IR3:IR4), resulting in the sequestration of the ErmA Shine-Dalgarno sequence and start codon within IR3:IR4. ErmA translation occurs when an inducing macrolide binds and stalls the ribosome during translation of the 19-mer peptide that overlaps IR1 (Fig. (Fig.1).1). The sequestration of IR1 by the stalled ribosome elicits hairpin formation between IR2 and IR3, thereby freeing the translation initiation elements downstream of IR3. In the 13 erythromycin- and clindamycin-susceptible isolates, no ErmA protein could be produced because the 48-bp deletion had removed its translation initiation elements. In contrast to previous reports of ermA alterations that resulted in constitutive erythromycin resistance (6, 7, 11), the 48-bp deletion in the ermA attenuation sequence represents a novel event that confers an erythromycin- and clindamycin-susceptible phenotype. Although this deletion event appears to be rare, ongoing monitoring is needed to determine its frequency over time.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".