Liu Fangjia, Wu Menghui, Shao Dan, Zhou Xueya, Liu Quan, Sheng Xijing, Li Donghua, Dai Menghong
The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China; MOA Key Laboratory of Food Safety Evaluation/National Reference Laboratory of Veterinary Drug Residue (HZAU), Huazhong Agricultural University, Wuhan, 430070, China.
The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China; MOA Key Laboratory of Food Safety Evaluation/National Reference Laboratory of Veterinary Drug Residue (HZAU), Huazhong Agricultural University, Wuhan, 430070, China.
Microb Pathog. 2025 Jun;203:107428. doi: 10.1016/j.micpath.2025.107428. Epub 2025 Feb 26.
as an important food-borne zoonotic pathogen, is found in soil and processing environment by human or animal feces, causing serious public health problems. Quaternary ammonium compounds (QACs) disinfectants are widely used in hospitals, livestock farms and food processing sites because of their low toxicity and broad-spectrum disinfection. However, sub-lethal levels of QACs disinfectants can induce bacteria to develop tolerance to disinfectants and cross-resistance to other antimicrobial agents. The acquired resistance will undoubtedly pose a threat to the prevention of antimicrobial resistance. In this study, Salmonella enterica SE211 was induced by the sub-inhibitory concentration and sub-lethal concentration of dodecyl dimethyl ammonium bromide (DDAB) in vitro. Following exposure to DDAB, the strains showed increased resistance to DDAB, doxycycline, amphenicols and fluoroquinolones, and increased sensitivity to colistin drugs. Phenotypic experiments showed that the induced strains exhibited changes in efflux pump activity, biofilm formation ability, motility and membrane characterization. Next-generation sequencing revealed mutations in induced strains involved in LPS-related genes (msbA, lptDE) and cationic antimicrobial peptide (CAMP) resistance-related genes (phoQ, pmrD). Transcriptome sequencing (RNA-seq) analysis revealed up-regulation of efflux pump genes and down-regulation of CAMP resistance, LPS and peptidoglycan related genes. Our study provided a theoretical basis for the potential consequences of disinfection failures and environmental residues of QACs disinfectants on the evolution of antibiotic resistance in salmonella. Furthermore, the induction of colistin sensitivity in salmonella by DDBA resulted in the emergence of collateral sensitivity, which offered a new strategy for drug combination applications to prevent the rise of colistin-resistant superbugs.
作为一种重要的食源性人畜共患病原体，通过人类或动物粪便存在于土壤和加工环境中，会引发严重的公共卫生问题。季铵化合物（QACs）消毒剂因其低毒性和广谱消毒作用而广泛应用于医院、养殖场和食品加工场所。然而，亚致死剂量的QACs消毒剂会诱导细菌产生对消毒剂的耐受性以及对其他抗菌剂的交叉耐药性。这种获得性耐药无疑会对抗菌药物耐药性的预防构成威胁。在本研究中，肠炎沙门氏菌SE211在体外被十二烷基二甲基溴化铵（DDAB）的亚抑制浓度和亚致死浓度诱导。暴露于DDAB后，菌株对DDAB、多西环素、氯霉素和氟喹诺酮类药物的耐药性增加，而对黏菌素类药物的敏感性增加。表型实验表明，诱导菌株在流出泵活性、生物膜形成能力、运动性和膜特性方面表现出变化。下一代测序揭示了诱导菌株中与脂多糖相关基因（msbA、lptDE）和阳离子抗菌肽（CAMP）耐药相关基因（phoQ、pmrD）的突变。转录组测序（RNA-seq）分析显示流出泵基因上调，而CAMP耐药、脂多糖和肽聚糖相关基因下调。我们的研究为QACs消毒剂消毒失败及环境残留对沙门氏菌抗生素耐药性演变的潜在后果提供了理论依据。此外，DDBA诱导沙门氏菌对黏菌素敏感导致了协同敏感性的出现，这为药物联合应用以预防耐黏菌素超级细菌的出现提供了一种新策略。
