Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.
Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Vet Res. 2021 Apr 29;52(1):63. doi: 10.1186/s13567-021-00934-w.
The TonB system is generally considered as an energy transporting device for the absorption of nutrients. Our recent study showed that deletion of this system caused a significantly increased sensitivity of Aeromonas hydrophila to the macrolides erythromycin and roxithromycin, but had no effect on other classes of antibiotics. In this study, we found the sensitivity of ΔtonB123 to all macrolides tested revealed a 8- to 16-fold increase compared with the wild-type (WT) strain, but this increase was not related with iron deprivation caused by tonB123 deletion. Further study demonstrated that the deletion of tonB123 did not damage the integrity of the bacterial membrane but did hinder the function of macrolide efflux. Compared with the WT strain, deletion of macAB, one of two ATP-binding cassette (ABC) types of the macrolide efflux pump, enhanced the sensitivity to the same levels as those of ΔtonB123. Interestingly, the deletion of macAB in the ΔtonB123 mutant did not cause further increase in sensitivity to macrolide resistance, indicating that the macrolide resistance afforded by the MacAB pump was completely abrogated by tonB123 deletion. In addition, macAB expression was not altered in the ΔtonB123 mutant, indicating that any influence of TonB on MacAB-mediated macrolide resistance was at the pump activity level. In conclusion, inactivation of the TonB system significantly compromises the resistance of A. hydrophila to macrolides, and the mechanism of action is related to the function of MacAB-mediated macrolide efflux.
TonB 系统通常被认为是一种能量转运装置，用于吸收营养物质。我们最近的研究表明，该系统的缺失会导致嗜水气单胞菌对大环内酯类抗生素红霉素和罗红霉素的敏感性显著增加，但对其他类别的抗生素没有影响。在本研究中，我们发现与野生型（WT）菌株相比，ΔtonB123 对所有测试的大环内酯类药物的敏感性增加了 8 到 16 倍，但这种增加与 tonB123 缺失引起的缺铁无关。进一步的研究表明，tonB123 的缺失不会破坏细菌膜的完整性，但确实会阻碍大环内酯类药物外排泵的功能。与 WT 菌株相比，macAB 的缺失（macrolide efflux pump 的两个 ATP 结合盒（ABC）类型之一）增强了对相同水平的大环内酯类药物的敏感性，与 ΔtonB123 的敏感性相同。有趣的是，macAB 在 ΔtonB123 突变体中的缺失并没有导致对大环内酯类药物抗性的进一步增加，表明 MacAB 泵赋予的大环内酯类药物抗性完全被 tonB123 的缺失所消除。此外，在 ΔtonB123 突变体中，macAB 的表达没有改变，表明 TonB 对 MacAB 介导的大环内酯类药物抗性的任何影响都在泵活性水平上。总之，TonB 系统的失活显著降低了嗜水气单胞菌对大环内酯类药物的耐药性，其作用机制与 MacAB 介导的大环内酯类药物外排泵的功能有关。
