Department of Microbiology, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia.
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA.
mSphere. 2021 Mar 10;6(2):e00033-21. doi: 10.1128/mSphere.00033-21.
is an emerging pathogen with increasing clinical importance due to its intrinsic resistance to several classes of antibiotics. The chromosomally encoded drug efflux pumps contribute to antibiotic resistance and represent a major challenge for the treatment of bacterial infections. The ABC-type efflux pump MacAB was previously linked to macrolide resistance in and serovar Typhimurium. The role of the MacAB homolog in antibiotic resistance of is currently unknown. We found that an mutant lacking the MacAB pump did not show increased sensitivity to the macrolide antibiotic erythromycin but was significantly more sensitive to aminoglycoside antibiotics and polymyxins. We also showed that, in addition to its role in drug efflux, the MacAB efflux pump is required for swimming motility and biofilm formation. We propose that the motility defect of the mutant is due, at least in part, to the loss of functional flagella on the bacterial surface. Furthermore, we found that the promoter of the MacAB efflux pump was active during the initial hours of growth in laboratory medium and that its activity was further elevated in the presence of hydrogen peroxide. Finally, we demonstrate a complete loss of mutant viability in the presence of peroxide, which is fully restored by complementation. Thus, the MacAB efflux pump is essential for survival during oxidative stress and is involved in protection from polymyxins and aminoglycoside antibiotics. The opportunistic pathogen can cause urinary tract infections, respiratory infections, meningitis, and sepsis in immunocompromised individuals. These infections are challenging to treat due to the intrinsic resistance of to an extensive array of antibiotics. Efflux pumps play a crucial role in protection of bacteria from antimicrobials. The MacAB efflux pump, previously linked to efflux of macrolides in and protection from oxidative stress in serovar Typhimurium, is not characterized in We show the role of the MacAB efflux pump in protection from aminoglycoside antibiotics and polymyxins, modulation of bacterial motility, and biofilm formation, and we illustrate the essential role for this pump in bacterial survival during oxidative stress. Our findings make the MacAB efflux pump an attractive target for inhibition to gain control over infections.
是一种具有日益重要临床意义的新兴病原体，由于其对几类抗生素的固有耐药性。染色体编码的药物外排泵有助于抗生素耐药性，是治疗细菌感染的主要挑战。ABC 型外排泵 MacAB 先前与 和 血清型鼠伤寒沙门氏菌中的大环内酯类耐药性有关。目前尚不清楚 中 MacAB 同源物在抗生素耐药性中的作用。我们发现缺乏 MacAB 泵的 突变体对大环内酯类抗生素红霉素没有表现出增加的敏感性，但对氨基糖苷类抗生素和多黏菌素明显更敏感。我们还表明，除了在药物外排中的作用外，MacAB 外排泵还需要用于游泳运动和生物膜形成。我们提出， 突变体的运动缺陷至少部分归因于细菌表面功能性鞭毛的丧失。此外，我们发现 MacAB 外排泵的启动子在实验室培养基中生长的最初几个小时内是活跃的，并且在存在过氧化氢时其活性进一步升高。最后，我们证明了 突变体在存在过氧化物时完全丧失了活力，而过氧化物的完全互补恢复了其活力。因此，MacAB 外排泵对于氧化应激期间的存活是必需的，并且参与了对多黏菌素和氨基糖苷类抗生素的保护。机会性病原体 可导致免疫功能低下个体的尿路感染、呼吸道感染、脑膜炎和败血症。由于 对广泛的抗生素固有耐药性，这些感染难以治疗。外排泵在保护细菌免受抗菌药物方面起着至关重要的作用。MacAB 外排泵先前与 和 血清型鼠伤寒沙门氏菌中的大环内酯类外排和氧化应激保护有关，但在 中尚未表征。我们显示了 MacAB 外排泵在 对氨基糖苷类抗生素和多黏菌素的保护、细菌运动性和生物膜形成的调节中的作用，并说明了该泵在细菌氧化应激期间生存中的重要作用。我们的发现使 MacAB 外排泵成为抑制的有吸引力的靶点，以控制 感染。
