Tian Yuqi, Wen Yaya, Wang Xueying, Zhang Youkun, Kang Xilong, Meng Chuang, Pan Zhiming, Jiao Xinan, Gu Dan
Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China.
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China.
PLoS Pathog. 2025 Mar 18;21(3):e1012951. doi: 10.1371/journal.ppat.1012951. eCollection 2025 Mar.
Salmonella enterica serovar 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a common nontyphoidal Salmonella serotype to cause human foodborne disease, exhibiting antibiotic and multidrug resistance. In this study, we identified the isolates of S. 4,[5],12:i:- resistant to quaternary ammonium compounds (QACs) disinfectants, displaying elevated minimum inhibitory concentration (MIC) values (200 μg/mL) in Mueller-Hinton (MH) broth. The efflux pump SugE1 and SugE2 could be induced by didecyldimethylammonium bromide (DDAB) and found to be indispensable for S. 4,[5],12:i:- resistance to DDAB. The Hoechst 33342 dye accumulation and reduced ethidium bromide efflux in ΔsugE1, ΔsugE2 and ΔsugE1ΔsugE2 further confirmed the efflux function of SugE1 and SugE2. Moreover, DDAB inhibited the expression of Salmonella pathogenicity island 1 (SPI-1) to decrease the adhesion and invasion ability of S. 4,[5],12:i:- in IPEC-J2 cells, whereas the deletion of sugE2 increased the adhesion and invasion ability. In an in vivo mice model, the virulence of ΔsugE2 and ΔsugE1ΔsugE2 mutant strains were enhanced and showed significantly increased bacterial loads in the liver, spleen, and cecum. The ΔsugE2 and ΔsugE1ΔsugE2 mutant strains exhibited an enhanced ability to disrupt the intestinal barrier, leading to systemic infection. Finally, we discovered that intestinal extracts could induce sugE1 and sugE2 expression, subsequently suppressing SPI-1 expression through SugE2, mediating the Salmonella intestinal infection process. In conclusion, our findings provide the pivotal role of the SugE2 efflux pump in conferring resistance to DDAB disinfectants and influencing bacterial virulence in S. 4,[5],12:i:-.
肠炎沙门氏菌血清型4,[5],12:i: - 是鼠伤寒沙门氏菌的单相变体，已成为引起人类食源性疾病的常见非伤寒沙门氏菌血清型，表现出抗生素和多重耐药性。在本研究中，我们鉴定了对季铵化合物（QACs）消毒剂耐药的肠炎沙门氏菌血清型4,[5],12:i: - 分离株，其在穆勒-欣顿（MH）肉汤中的最低抑菌浓度（MIC）值升高（200μg/mL）。外排泵SugE1和SugE2可被二癸基二甲基溴化铵（DDAB）诱导，并且发现它们对于肠炎沙门氏菌血清型4,[5],12:i: - 对DDAB的耐药性是必不可少的。在ΔsugE1、ΔsugE2和ΔsugE1ΔsugE2中，Hoechst 33342染料积累增加和溴化乙锭外排减少进一步证实了SugE1和SugE2的外排功能。此外，DDAB抑制沙门氏菌致病岛1（SPI-1）的表达，以降低肠炎沙门氏菌血清型4,[5],12:i: - 在IPEC-J2细胞中的粘附和侵袭能力，而sugE2的缺失则增加了其粘附和侵袭能力。在体内小鼠模型中，ΔsugE2和ΔsugE1ΔsugE2突变株的毒力增强，并且在肝脏、脾脏和盲肠中的细菌载量显著增加。ΔsugE2和ΔsugE1ΔsugE2突变株表现出破坏肠道屏障的能力增强，导致全身感染。最后，我们发现肠道提取物可以诱导sugE1和sugE2的表达，随后通过SugE2抑制SPI-1的表达，介导沙门氏菌肠道感染过程。总之，我们的研究结果表明SugE2外排泵在肠炎沙门氏菌血清型4,[5],12:i: - 对DDAB消毒剂的耐药性及影响细菌毒力方面起着关键作用。
