Fluoroquinolone susceptibility of wild-type Listeria monocytogenes isolates and the role of FepR and ParC mutations in conferring fluoroquinolone tolerance
Bibliographic record
Abstract
Fluoroquinolone response and associated genotypic variants were characterized in a set of 88 Listeria monocytogenes strains isolated from Canadian dairy facilities over a span of 10 years. All strains were susceptible to ciprofloxacin (CIP), moxifloxacin (MOX), and levofloxacin (LEV) using the VITEK GP-AST75 assay. However, CIP minimum inhibitory concentrations (MICs) varied in the broth dilution assay, with 47 isolates exhibiting MICs of 1 ppm and 41 isolates at ≤0.5 ppm (detection limit). Isolates with elevated MICs to one fluoroquinolone showed correlated increases in MICs to other fluoroquinolones (Spearman's correlation; p < 0.0001). MICs were confirmed using a broth dilution assay (0.125-8 ppm; two-fold dilution in MHB), with variable growth observed among replicates at sublethal CIP concentrations. After two passages in 0.5 ppm CIP, WRLP81 exhibited increased fitness (reduced lag phase duration) and MIC increases in CIP (4 ppm), LEV (2 ppm), and MOX (1 ppm). Whole genome sequencing of descendants (81.2B; 81.2C) revealed two unique frameshift mutations in fepR: V114fs and Glu139fs. Molecular modeling predicted conformational defects likely impairing FepA dimerization and efflux pump repression. Similarly, after two passages in 0.5 ppm CIP, a WRLP86 descendant (86.2C_2) exhibited increased MICs for CIP (2 ppm), LEV (4 ppm), and MOX (1 ppm), linked to a parC missense mutation that altered the winged helix domain. This amino acid change likely creates steric interference near the fluoroquinolone binding pocket and represents the first report of a parC mutation identified in L. monocytogenes in response to sublethal CIP exposure. This research highlights the rapid and varied adaptation of reduced fluoroquinolone susceptibility in L. monocytogenes.
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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".