Aminoglycoside Efflux in <i>Pseudomonas aeruginosa</i> : Involvement of Novel Outer Membrane Proteins
Bibliographic record
Abstract
The expression of tripartite multidrug efflux pumps such as MexA-MexB-OprM in Pseudomonas aeruginosa contributes to intrinsic resistance to a wide variety of antimicrobials, including beta-lactams, chloramphenicol, macrolides, quinolones, and tetracycline. The MexX-MexY linker-pump combination has been shown to be involved in intrinsic resistance to aminoglycosides, but the identity of the cognate outer membrane channel component remains under debate. Fourteen uncharacterized OprM homologs identified in the genome of P. aeruginosa were examined as candidates for this role by assessing the minimum inhibitory concentrations (MICs) of aminoglycosides in P. aeruginosa strain PAK knockout mutants lacking the corresponding genes. Insertional inactivation of OpmG, OpmI, and OpmH resulted in decreases of various degrees in the MICs of streptomycin, kanamycin, and gentamicin. When reintroduced into P. aeruginosa on multicopy plasmids, OpmG was able to complement the susceptibility of an opmG::miniTn5 mutant; however, cloned opmH, the proposed ortholog of Escherichia coli tolC according to our phylogenetic analysis, was able to only partially complement the opmH::miniTn5 mutant. Mini-microarray hybridization analysis demonstrated that opmG disruption does not affect expression of OpmI or OpmH (ruling out such indirect effects on aminoglycoside resistance); however, opmH disruption did have possible effects on expression of OpmG and OpmI. Based on the data, we propose that OpmG is a major outer membrane efflux channel involved in aminoglycoside efflux in P. aeruginosa PAK and that OpmI, its most related paralog, may share an overlapping function.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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 teacher head, 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".