College of Life Sciences, Sichuan University, Chengdu, PR China; Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, Chengdu, PR China; Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, Chengdu, PR China.
Luzhou Pinchuang Technology Co. Ltd., Luzhou, PR China; National Engineering Research Center of Solid-State Brewing, Luzhou Laojiao Co. Ltd., Luzhou, PR China.
Microb Pathog. 2024 Nov;196:106982. doi: 10.1016/j.micpath.2024.106982. Epub 2024 Sep 25.
Salmonella is a major foodborne pathogen that can be transmitted from livestock and poultry to humans through the food chain. Due to the widespread use of antibiotics, antibiotic resistance Salmonella has become an important factor threatening food safety. Combining antibiotic and non-antibiotic agents is a promising approach to address the widespread emergence of antibiotic-resistant pathogens. In this study, we investigated the antibiotic resistance profile and molecular characterization of different serotypes of Salmonella isolated from large-scale egg farms using drug susceptibility testing and whole genome sequencing. The synergistic effect of alpha-linolenic acid (ALA) with antibiotics was evaluated using the checkerboard test and time-kill curve. The molecular mechanism of α-linolenic acid synergism was explored using biochemical assays, pull-down assays, and molecular docking. In vivo efficacy of ALA in combination with florfenicol (FFC) or tetracycline (TET) against multidrug-resistant (MDR) Salmonella enterica subsp. enterica serovar typhimurium was also investigated using a mouse model. We found that ALA reduced the minimum inhibitory concentration (MIC) of tetracycline and florfenicol in all strains tested. When ALA (512 mg/L) was combined with florfenicol (32 mg/L) or tetracycline (16 mg/L), we observed disruption of cell membrane integrity, increased outer membrane permeability, lowered cell membrane potential, and inhibition of proton-drive-dependent efflux pumps. The synergistic treatment also inhibited biofilm production and promoted oxidative damage. These changes together led to an increase in bacterial antibiotic susceptibility. The improved efficacy of ALA combination treatment with antibiotics was validated in the mouse model. Molecular docking results indicate that ALA can bind to membrane proteins via hydrogen bonding. Our findings demonstrated that combined treatment using ALA and antibiotics is effective in preventing infections involving MDR bacteria. Our results are of great significance for the scientific and effective prevention and control of antibiotic resistance Salmonella, as well as ensuring food safety.
沙门氏菌是一种主要的食源性病原体，可以通过食物链从牲畜和家禽传播给人类。由于抗生素的广泛使用，抗生素耐药性沙门氏菌已成为威胁食品安全的重要因素。将抗生素与非抗生素药物联合使用是解决抗生素耐药性病原体广泛出现的一种有前途的方法。在这项研究中，我们使用药物敏感性测试和全基因组测序，研究了从大型蛋鸡养殖场分离的不同血清型沙门氏菌的抗生素耐药谱和分子特征。通过棋盘试验和时间杀伤曲线评估了 α-亚麻酸（ALA）与抗生素的协同作用。通过生化测定、下拉测定和分子对接探讨了 α-亚麻酸协同作用的分子机制。还使用小鼠模型研究了 ALA 与氟苯尼考（FFC）或四环素（TET）联合使用对多重耐药（MDR）鼠伤寒沙门氏菌的体内疗效。我们发现 ALA 降低了所有测试菌株中甲氧苄啶和氟苯尼考的最小抑菌浓度（MIC）。当 ALA（512mg/L）与氟苯尼考（32mg/L）或四环素（16mg/L）联合使用时，我们观察到细胞膜完整性受到破坏，外膜通透性增加，细胞膜电位降低，质子驱动依赖性外排泵受到抑制。协同治疗还抑制了生物膜的产生并促进了氧化损伤。这些变化共同导致细菌对抗生素的敏感性增加。在小鼠模型中验证了 ALA 联合抗生素治疗的效果得到了改善。分子对接结果表明，ALA 可以通过氢键与膜蛋白结合。我们的研究结果表明，使用 ALA 和抗生素联合治疗对预防涉及 MDR 细菌的感染是有效的。我们的研究结果对科学有效地预防和控制抗生素耐药性沙门氏菌以及确保食品安全具有重要意义。
Appl Environ Microbiol. 2018-9-17
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