解析对季铵化合物的易感性：基因、表型及环境条件的影响 - Suppr | 超能文献

Abstract

Quaternary ammonium compounds (QACs) have been extensively used in the community, healthcare facilities, and food chain, in concentrations between 20 and 30,000 mg/L. and are ubiquitous in these settings and are recognized as nosocomial pathogens worldwide, but QACs' activity against strains from diverse epidemiological and genomic backgrounds remained largely unexplored. We evaluated the role of isolates from different sources, years, and clonal lineages as hosts of QACs tolerance genes and their susceptibility to QACs in optimal, single-stress and cross-stress growth conditions. Only 1% of the isolates included in this study and 0.5% of publicly available genomes carried or genes, shared with >60 species of Bacillota, Pseudomonadota, Actinomycetota, or Spirochaetota. These genes were generally found within close proximity of antibiotics and/or metals resistance genes. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of benzalkonium chloride (BC) and didecyldimethylammonium chloride ranged between 0.5 and 4 mg/L (microdilution: 37°C/20 h/pH = 7/aerobiosis) for 210 and isolates (two isolates carrying ). Modified growth conditions (e.g., 22°C/pH = 5) increased MIC/MBC (maximum of eightfold and MBC = 16 mg/L) and changed bacterial growth kinetics under BC toward later stationary phases in both species, including in isolates without QACs tolerance genes. In conclusion, are susceptible to in-use QACs concentrations and rarely carry QACs tolerance genes. However, their potential gene exchange with different microbiota, the decreased susceptibility to QACs under specific environmental conditions, and the presence of subinhibitory QACs concentrations in various settings may contribute to the selection of particular strains and, thus, require a One Health strategy to maintain QACs effectiveness. IMPORTANCE Despite the increasing use of quaternary ammonium compounds (QACs), the susceptibility of pathogens to these antimicrobials remains largely unknown. and are susceptible to in-use QACs concentrations and are not main hosts of QACs tolerance genes but participate in gene transfer pathways with diverse bacterial taxa exposed to these biocides. Moreover, QACs tolerance genes often share the same genetic contexts with antibiotics and/or metals resistance genes, raising concerns about potential co-selection events. and showed increased tolerance to benzalkonium chloride under specific environmental conditions (22°C, pH = 5), suggesting that strains might be selected in settings where they occur along with subinhibitory QACs concentrations. Transcriptomic studies investigating the cellular mechanisms of adaptation to QACs tolerance, along with longitudinal metadata analysis of tolerant populations dynamics under the influence of diverse environmental factors, are essential and should be prioritized within a One Health strategy.

摘要

季铵化合物（QACs）已在社区、医疗机构和食物链中广泛使用，浓度范围为20至30000 mg/L。它们在这些环境中普遍存在，并且在全球范围内被认为是医院病原体，但QACs对来自不同流行病学和基因组背景菌株的活性在很大程度上仍未得到探索。我们评估了来自不同来源、年份和克隆谱系的菌株作为QACs耐受基因宿主的作用，以及它们在最佳、单一应激和交叉应激生长条件下对QACs的敏感性。本研究中纳入的菌株只有1%，公开可用的基因组中只有0.5%携带与60多种芽孢杆菌门、假单胞菌门、放线菌门或螺旋体门共有的qacA或qacB基因。这些基因通常位于抗生素和/或金属抗性基因附近。对于210株金黄色葡萄球菌和表皮葡萄球菌菌株（两株携带qacA基因），苯扎氯铵（BC）和二癸基二甲基氯化铵的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）在0.5至4 mg/L之间（微量稀释法：37°C/20小时/pH = 7/需氧培养）。改良的生长条件（例如，22°C/pH = 5）会增加MIC/MBC（最高可达八倍，MBC = 16 mg/L），并使两种菌在BC作用下的细菌生长动力学向后期稳定期转变，包括那些没有QACs耐受基因的菌株。总之，金黄色葡萄球菌和表皮葡萄球菌对实际使用的QACs浓度敏感，很少携带QACs耐受基因。然而，它们与不同微生物群潜在的基因交换、在特定环境条件下对QACs敏感性的降低以及各种环境中存在亚抑菌浓度的QACs，可能会导致特定菌株的选择，因此需要一种“同一健康”策略来维持QACs的有效性。重要性尽管季铵化合物（QACs）的使用越来越多，但病原体对这些抗菌剂的敏感性在很大程度上仍然未知。金黄色葡萄球菌和表皮葡萄球菌对实际使用的QACs浓度敏感，不是QACs耐受基因的主要宿主，但参与了与接触这些杀菌剂的不同细菌类群的基因转移途径。此外，QACs耐受基因通常与抗生素和/或金属抗性基因共享相同的遗传背景，这引发了对潜在共选择事件的担忧。金黄色葡萄球菌和表皮葡萄球菌在特定环境条件（22°C，pH = 5）下对苯扎氯铵的耐受性增加，这表明在存在亚抑菌浓度QACs的环境中可能会选择出这些菌株。研究金黄色葡萄球菌适应QACs耐受的细胞机制的转录组学研究，以及在不同环境因素影响下对耐受种群动态的纵向元数据分析，至关重要，应在“同一健康”策略中优先进行。