Beirne Catriona, McCann Emily, McDowell Andrew, Miliotis Georgios
Antimicrobial Resistance and Microbial Ecology Group, School of Medicine, National University of Ireland, Galway, Ireland.
Nutrition Innovation Centre for Food and Health, (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Ireland.
Access Microbiol. 2022 Aug 11;4(8):acmi000404. doi: 10.1099/acmi.0.000404. eCollection 2022.
Using available whole genome data, the objective of this study was to identify genetic mechanisms that could explain the antimicrobial resistance profile of three multi-drug resistant (MDR) strains (CA17, CA51, CA39) of the skin bacterium previously recovered from patients with acne. In particular, we were interested in detecting novel genetic determinants associated with resistance to fluoroquinolone and macrolide antibiotics that could then be confirmed experimentally.
A range of open source bioinformatics tools were used to 'mine' genetic determinants of antimicrobial resistance and plasmid borne contigs, and to characterise the phylogenetic diversity of the MDR strains.
As probable mechanisms of resistance to fluoroquinolones, we identified a previously described resistance associated allelic variant of the gene with a 'deleterious' S101L mutation in type IA strains CA51 (ST1) and CA39 (ST1), as well as a novel E761R 'deleterious' mutation in the type II strain CA17 (ST153). A distinct genomic sequence of the efflux protein YfmO which is potentially associated with resistance to MLSB antibiotics was also present in CA17; homologues in CA51, CA39, and other strains of , were also found but differed in amino acid content. Strikingly, in CA17 we also identified a circular 2.7 kb non-conjugative plasmid (designated pCA17) that closely resembled a 4.8 kb plasmid (pYU39) from the MDR strain YU39.
This study has provided a detailed explanation of potential genetic determinants for MDR in the strains CA17, CA39 and CA51. Further laboratory investigations will be required to validate these results, especially in relation to pCA17.
利用现有的全基因组数据，本研究旨在确定能够解释先前从痤疮患者中分离出的三种皮肤细菌多药耐药（MDR）菌株（CA17、CA51、CA39）抗菌耐药谱的遗传机制。特别地，我们感兴趣的是检测与氟喹诺酮和大环内酯类抗生素耐药相关的新遗传决定因素，随后通过实验进行确认。
使用一系列开源生物信息学工具来“挖掘”抗菌耐药性的遗传决定因素和质粒携带的重叠群，并对MDR菌株的系统发育多样性进行表征。
作为对氟喹诺酮耐药的可能机制，我们在IA型菌株CA51（ST1）和CA39（ST1）中鉴定出一个先前描述的与耐药相关的等位基因变体，该基因存在“有害的”S101L突变，以及在II型菌株CA17（ST153）中发现一个新的E761R“有害的”突变。CA17中还存在一种与MLSB抗生素耐药潜在相关的外排蛋白YfmO的独特基因组序列；在CA51、CA39以及其他菌株中也发现了同源物，但氨基酸含量不同。令人惊讶的是，在CA17中我们还鉴定出一个环状2.7 kb非接合性质粒（命名为pCA17），它与MDR菌株YU39的4.8 kb质粒（pYU39）非常相似。
本研究详细解释了CA17、CA39和CA51菌株中MDR的潜在遗传决定因素。需要进一步的实验室研究来验证这些结果，特别是关于pCA17的结果。
