Australian Centre for Water and Environmental Biotechnology (ACWEB, Formerly AWMC), The University of Queensland, Brisbane, QLD, 4072, Australia.
Institute for Hydrobiology, Technische Universität Dresden, 01217, Dresden, Germany.
Microbiome. 2022 Aug 12;10(1):124. doi: 10.1186/s40168-022-01314-y.
Horizontal gene transfer (HGT) plays a critical role in the spread of antibiotic resistance and the evolutionary shaping of bacterial communities. Conjugation is the most well characterized pathway for the spread of antibiotic resistance, compared to transformation and transduction. While antibiotics have been found to induce HGT, it remains unknown whether non-antibiotic pharmaceuticals can facilitate conjugation at a microbial community-wide level.
In this study, we demonstrate that several commonly consumed non-antibiotic pharmaceuticals (including carbamazepine, ibuprofen, naproxen and propranolol), at environmentally relevant concentrations (0.5 mg/L), can promote the conjugative transfer of IncP1-α plasmid-borne antibiotic resistance across entire microbial communities. The over-generation of reactive oxygen species in response to these non-antibiotic pharmaceuticals may contribute to the enhanced conjugation ratios. Cell sorting and 16S rRNA gene amplicon sequencing analyses indicated that non-antibiotic pharmaceuticals modulate transconjugant microbial communities at both phylum and genus levels. Moreover, microbial uptake ability of the IncP1-α plasmid was also upregulated under non-antibiotic pharmaceutical exposure. Several opportunistic pathogens, such as Acinetobacter and Legionella, were more likely to acquire the plasmid conferring multidrug resistance.
Considering the high possibility of co-occurrence of pathogenic bacteria, conjugative IncP1-α plasmids and non-antibiotic pharmaceuticals in various environments (e.g., activated sludge systems), our findings illustrate the potential risk associated with increased dissemination of antibiotic resistance promoted by non-antibiotic pharmaceuticals in complex environmental settings. Video abstract.
水平基因转移（HGT）在抗生素耐药性的传播和细菌群落的进化塑造中起着关键作用。与转化和转导相比， conjugation 是抗生素耐药性传播的最典型途径。虽然已经发现抗生素会诱导 HGT，但仍不清楚非抗生素类药物是否可以在微生物群落水平上促进 conjugation。
在这项研究中，我们证明了几种常见的非抗生素类药物（包括卡马西平、布洛芬、萘普生和普萘洛尔）在环境相关浓度（0.5mg/L）下可以促进 IncP1-α 质粒携带的抗生素耐药性在整个微生物群落中的共轭转移。这些非抗生素类药物会引起过量的活性氧生成，这可能有助于提高共轭比。细胞分选和 16S rRNA 基因扩增子测序分析表明，非抗生素类药物会在门和属水平上调节转染微生物群落。此外，在非抗生素药物暴露下，IncP1-α 质粒的微生物摄取能力也被上调。一些机会性病原体，如不动杆菌和军团菌，更有可能获得赋予多药耐药性的质粒。
考虑到在各种环境（例如活性污泥系统）中，病原菌、可接合的 IncP1-α 质粒和非抗生素类药物同时存在的可能性很高，我们的研究结果表明，在复杂的环境中，非抗生素类药物促进抗生素耐药性传播的潜在风险增加。
