Abstract
Bacterial antibiotic resistance is a serious global problem; the underlying regulatory mechanisms are largely elusive. The earlier reports states that the vital role of transcriptional regulators (TRs) in bacterial antibiotic resistance. Therefore, we have investigated the role of TRs on enoxacin (ENX) resistance in Aeromonas hydrophila in this study. A label-free quantitative proteomics method was utilized to compare the protein profiles of the ahslyA knockout and wild-type A. hydrophila strains under ENX stress. Bioinformatics analysis showed that the deletion of ahslyA triggers the up-regulated expression of some vital antibiotic resistance proteins in A. hydrophila upon ENX stress and thereby reduce the pressure by preventing the activation of SOS repair system. Moreover, ahslyA directly or indirectly induced at least 11 TRs, which indicates a complicated regulatory network under ENX stress. We also deleted six selected genes in A. hydrophila that altered in proteomics data in order to evaluate their roles in ENX stress. Our results showed that genes such as AHA_0655, narQ, AHA_3721, AHA_2114, and AHA_1239 are regulated by ahslyA and may be involved in ENX resistance. Overall, our data demonstrated the important role of ahslyA in ENX resistance and provided novel insights into the effects of transcriptional regulation on antibiotic resistance in bacteria.
Highlights
Antibiotic-resistant bacterial strains were discovered over 90 years ago
In order to better understand the characteristics of the transcriptional regulators (TRs) AhslyA on bacterial antibiotic resistance, we first constructed ahslyA mutant strain and tested its antibiotic susceptibilities against various antibiotics, including several quinolone antibiotics
Complementation of the ahslyA strain restored the antibiotic susceptibilities similar level to the WT strain, which is suggesting that the ahslyA gene in A. hydrophila is involved in the regulation of several antibiotic resistances, especially ENX
Summary
Antibiotic-resistant bacterial strains were discovered over 90 years ago. Since antibioticresistant bacterial strains have been found to be widely distributed in various environments, such as in hospitals, seafood, and aquaculture farms, and as a result, they pose a serious public health problem worldwide (Fritsche et al, 2009; Peng et al, 2015). Bacterial TRs play an important role in the transcriptional regulation of functional genes needed to survive environmental stresses, including antibiotic resistance (Zhou and Yang, 2006; Tang et al, 2019a). We reported that the LysRtype TR YeeY in A. hydrophila plays an important role in the regulation of furazolidone resistance by directly regulating ARGs, including AHA_3222 and AHA_4275 It indicates the crucial role of TRs in the antibiotic resistance of this pathogen. Previous research reported the homologous proteins of this TR in other bacterial species play diverse biological functions such as cell metabolism and virulence, while its biological effect and molecular mechanism are still largely unknown, especially for the bacterial antibiotics resistance in A. hydrophila (Banda et al, 2019; Tian et al, 2021). This study will conduce to further understand the complicated antibiotic resistance mechanisms mediated by bacterial TRs
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