Kang Minjeong, Choi Tae-Rim, Ahn Soyeon, Heo Hee Young, Kim Hyerim, Lee Hye Soo, Lee Yoo Kyung, Joo Hwang-Soo, Yune Philip S, Kim Wooseong, Yang Yung-Hun
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea.
Department of Biological Engineering, College of Engineering, Konkuk University, Seoul 05029, Korea.
Antibiotics (Basel). 2022 Jul 29;11(8):1019. doi: 10.3390/antibiotics11081019.
Bacteria can evade antibiotics by acquiring resistance genes, as well as switching to a non-growing dormant state without accompanying genetic modification. Bacteria in this quiescent state are called persisters, and this non-inheritable ability to withstand multiple antibiotics is referred to as antibiotic tolerance. Although all bacteria are considered to be able to form antibiotic-tolerant persisters, the antibiotic tolerance of extremophilic bacteria is poorly understood. Previously, we identified the psychrotolerant bacterium Pseudomonas sp. B14-6 from the glacier foreland of Midtre Lovénbreen in High Arctic Svalbard. Herein, we investigated the resistance and tolerance of Pseudomonas sp. B14-6 against aminoglycosides at various temperatures. This bacterium was resistant to streptomycin and susceptible to apramycin, gentamicin, kanamycin, and tobramycin. The two putative aminoglycoside phosphotransferase genes aph1 and aph2 were the most likely contributors to streptomycin resistance. Notably, unlike the mesophilic Pseudomonas aeruginosa PA14, this cold-adapted bacterium demonstrated reduced susceptibility to all tested aminoglycosides in a temperature-dependent manner. Pseudomonas sp. B14-6 at a lower temperature formed the persister cells that shows tolerance to the 100-fold minimum inhibitory concentration (MIC) of gentamicin, as well as the partially tolerant cells that withstand 25-fold MIC gentamicin. The temperature-dependent gentamicin tolerance appears to result from reduced metabolic activity. Lastly, the partially tolerant Pseudomonas sp. B14-6 cells could slowly proliferate under the bactericidal concentrations of aminoglycosides. Our results demonstrate that Pseudomonas sp. B14-6 has a characteristic ability to form cells with a range of tolerance, which appears to be inversely proportional to its growth rate.
细菌可以通过获取耐药基因以及转变为不生长的休眠状态(无需伴随基因修饰)来逃避抗生素。处于这种静止状态的细菌被称为持留菌,这种耐受多种抗生素的非遗传性能力被称为抗生素耐受性。尽管所有细菌都被认为能够形成耐受抗生素的持留菌,但嗜极菌的抗生素耐受性却知之甚少。此前,我们从北极斯瓦尔巴群岛中特雷·洛文冰川前沿分离出了耐冷细菌假单胞菌属B14 - 6。在此,我们研究了假单胞菌属B14 - 6在不同温度下对氨基糖苷类抗生素的抗性和耐受性。该细菌对链霉素耐药,对阿普拉霉素、庆大霉素、卡那霉素和妥布霉素敏感。两个假定的氨基糖苷磷酸转移酶基因aph1和aph2最有可能是导致链霉素耐药的原因。值得注意的是,与嗜温的铜绿假单胞菌PA14不同,这种适应寒冷的细菌对所有测试的氨基糖苷类抗生素的敏感性都以温度依赖的方式降低。较低温度下的假单胞菌属B14 - 6形成了对庆大霉素最低抑菌浓度(MIC)100倍具有耐受性的持留菌细胞,以及能耐受庆大霉素25倍MIC的部分耐受细胞。温度依赖性庆大霉素耐受性似乎是由代谢活性降低导致的。最后,部分耐受的假单胞菌属B14 - 6细胞在氨基糖苷类抗生素的杀菌浓度下能够缓慢增殖。我们的结果表明,假单胞菌属B14 - 6具有形成一系列耐受性细胞的独特能力,这种能力似乎与其生长速率成反比。