| Topic | Key finding | Study/system | Quantitative data | Publication (year, journal) and URL | Citation ID |
|---|---|---|---|---|---|
| Reaction/substrate | E. coli Mph(A) is a macrolide 2'-phosphotransferase/kinase that phosphorylates the amino sugar of macrolides and efficiently inactivates 14-membered macrolides such as erythromycin and the 15-membered macrolide azithromycin; Mph(A) uses GTP exclusively as phosphate donor. | Structural/biochemical characterization of MPH(2')-I from E. coli and Mph family enzymes | Qualitative substrate scope: 14- and 15-membered macrolides; exclusive GTP use | Fong et al., 2017, *Structure*; https://doi.org/10.1016/j.str.2017.03.007 | (pqac-00000003) |
| Reaction/substrate | Mph-family enzymes catalyze transfer of the γ-phosphate from GTP to the 2'-OH of macrolides; Mph(A) belongs to the clinically important mobile mph(A)-mph(O) family and is associated mainly with resistance to 14- and 15-membered macrolides. | Review of enzyme-mediated macrolide resistance | Qualitative family-level mechanistic summary | Golkar et al., 2018, *Frontiers in Microbiology*; https://doi.org/10.3389/fmicb.2018.01942 | (pqac-00000000) |
| Regulation | The E. coli mph(A)-mrx-mphR(A) cluster is inducible by erythromycin; MphR(A) is a TetR/AcrR-like repressor that binds the mph(A) promoter and is released by macrolides, causing derepression. | E. coli mph(A) regulatory locus | 2.9-kb inducible transcript detected; 14-membered macrolides inhibited MphR(A)-DNA binding at ~100-fold lower concentrations than representative 16-membered macrolides | Noguchi et al., 2000, *Journal of Bacteriology*; https://doi.org/10.1128/jb.182.18.5052-5058.2000 | (pqac-00000001, pqac-00000004, pqac-00000006) |
| Regulation/phenotype | mph(A) alone confers low-level erythromycin resistance, while co-carriage with mrx yields high-level resistance; mrx is hydrophobic and required for full Mph(A) expression/resistance phenotype. | E. coli plasmid constructs carrying mph(A) with/without mrx | Qualitative comparison: low-level vs high-level EM resistance depending on mrx presence | Noguchi et al., 2000, *Journal of Bacteriology*; https://doi.org/10.1128/jb.182.18.5052-5058.2000 | (pqac-00000001) |
| Genetic context | In a clinical E. coli ST69 isolate, mphA occurred in an IS26-composite transposon as the module IS26-mphA-mrx(A)-mphR(A)-IS6100 on a hybrid IncF plasmid carrying multiple resistance genes. | E. coli EC6868 (ST69), hospital isolate | ~18.9-kb IS26 composite transposon; isolate year 2017 | Wang et al., 2024, *Infection and Drug Resistance*; https://doi.org/10.2147/idr.s427571 | (pqac-00000011) |
| Genetic context | The same 18.9-kb mphA module is widely disseminated across Enterobacterales plasmids/chromosomes, especially IncF plasmids in E. coli, indicating strong mobility of the mphA-mrx(A)-mphR(A) cassette. | Comparative plasmid/genome analysis across Enterobacterales | 75/77 plasmids harboring the 18.9-kb structure were IncF (97.4%); 81 plasmids analyzed overall | Wang et al., 2024, *Infection and Drug Resistance*; https://doi.org/10.2147/idr.s427571 | (pqac-00000011) |
| Surveillance/prevalence | Large-scale European surveillance found mph(A) among the principal azithromycin-resistance determinants in E. coli and Salmonella and showed that different mph(A) operon structures were associated with susceptible versus resistant isolates. | EU harmonized AMR surveillance plus Danish surveillance | 1,007 E. coli analyzed, including 165 azithromycin-resistant isolates (MIC >16 mg/L); 269 Salmonella, including 29 resistant isolates; overall genotype-phenotype concordance 69% in E. coli and 92% in Salmonella | Ivanova et al., 2024, *Journal of Antimicrobial Chemotherapy*; https://doi.org/10.1093/jac/dkae161 | (pqac-00000008, pqac-00000012) |
| MIC/phenotype | In pediatric azithromycin-resistant Salmonella, all resistant isolates carried mphA and showed high AZM MICs, supporting mphA as a major high-level azithromycin resistance determinant in Enterobacterales. | 15 azithromycin-resistant Salmonella enterica isolates from children, Shenzhen | Resistance rate 3.08% (15/487); MIC distribution: 53.33% at 32 µg/mL, 20.0% at 64 µg/mL, 26.67% at 256 µg/mL; all 15/15 carried mphA | Wang et al., 2023, *Frontiers in Cellular and Infection Microbiology*; https://doi.org/10.3389/fcimb.2023.1116172 | (pqac-00000014, pqac-00000009) |
| Genetic context | mphA-bearing plasmids in Salmonella showed a conserved mobile backbone centered on an IS-mphA-tap structure and occurred on multiple plasmid types, with evidence for cross-species exchange with E. coli plasmids. | Shenzhen Salmonella plasmid analysis | All 15 mphA-positive contigs shared a core IS-mphA-tap structure; 8 distinct plasmids among 15 isolates; some homologous to E. coli plasmids at >99.9% identity | Wang et al., 2023, *Frontiers in Cellular and Infection Microbiology*; https://doi.org/10.3389/fcimb.2023.1116172 | (pqac-00000010) |
| MIC/phenotype | In Bangladesh Shigella, plasmid-borne mphA was associated with very high azithromycin resistance and was experimentally transferable into E. coli, confirming phenotype transfer by horizontal gene transfer. | Shigella donors and E. coli K-12 transconjugants | 42/59 isolates were AZM-resistant; MRP plasmid more frequent in resistant vs susceptible strains (60%, 25/42 vs 24%, 4/17; p<0.0001); transferred plasmid size 63 MDa; all transconjugants had AZM MIC ≥256 µg/mL | Asad et al., 2024, *Scientific Reports*; https://doi.org/10.1038/s41598-024-57423-1 | (pqac-00000013, pqac-00000016, pqac-00000017) |
| Interventions | Combination treatment that increased outer-membrane permeability (colistin plus azithromycin) reduced mph(A) expression/activity and restored azithromycin susceptibility in multidrug-resistant E. coli, suggesting Mph(A)-linked resistance can be partly overcome pharmacologically. | Multidrug-resistant E. coli T28R | 48 differentially expressed genes under combination treatment; mph(A) downregulated relative to azithromycin alone | Luo et al., 2024, *Microbiology Spectrum*; https://doi.org/10.1128/spectrum.03918-23 | (pqac-00000007) |


*Table: This table compiles mechanistic, regulatory, epidemiologic, and phenotypic evidence for the Enterobacterales macrolide resistance gene mphA/Mph(A), emphasizing E. coli where possible. It is useful as a concise evidence map linking biochemical function to mobile genetic context and recent surveillance findings.*