Working Paper Article Version 1 This version is not peer-reviewed

Transcriptomic Changes and satP Gene Function Analysis in Pasteurella multocida With Different Levels of Resistance to Fluoroquinolones

Version 1 : Received: 15 July 2021 / Approved: 20 July 2021 / Online: 20 July 2021 (14:48:06 CEST)

How to cite: Xu, G.; HAQMAL MOHAMMAD, A.; Xu, Y.; Xue, J.; Muhammad, I.; Zhang, H.; Li, X.; Jia, Y.; Wang, Y.; He, C.; Kong, L.; Ma, H. Transcriptomic Changes and satP Gene Function Analysis in Pasteurella multocida With Different Levels of Resistance to Fluoroquinolones. Preprints 2021, 2021070454 Xu, G.; HAQMAL MOHAMMAD, A.; Xu, Y.; Xue, J.; Muhammad, I.; Zhang, H.; Li, X.; Jia, Y.; Wang, Y.; He, C.; Kong, L.; Ma, H. Transcriptomic Changes and satP Gene Function Analysis in Pasteurella multocida With Different Levels of Resistance to Fluoroquinolones. Preprints 2021, 2021070454

Abstract

Under the pressure of fluoroquinolones, Pasteurella multocida (PM) can easily develop resistance to fluoroquinolones mediated by QRDR target mutation. It is imperative to find new drug resistance inhibitor targets to combat the rapid development of drug resistance. In order to overcome these problems, we sequenced the transcriptome of PM with different levels of resistance to ENR(0.03 μg/mL; 8 μg/mL; 32μg/Ml, Enrofloxacin). The results showed that with the increase of resistance to fluoroquinolones, the expression of satP gene was significantly up-regulated. The satP gene deletion strain and replenishment strain were constructed, and their drug resistance and tolerance were determined. The results showed that the deletion of satP gene did not affect the resistance of PM to fluoroquinolones, rather affected the time when PM developed resistance to fluoroquinolones. After 10 generations of drug induction, the MIC (minimum inhibitory concentration) of fluoroquinolones for wild strain was 64 μg/mL, while the MIC for satP gene deletion strain was only 8 μg/mL. The MDK99 test (time to kill 99% bacteria),agar diffusion test and mutation frequency test showed that the tolerance of satP gene deletion strain was significantly lower than that of wild strain. At the same time, the virulence of gene deletion strain and wild strain was tested, and about 400 times decreased virulence was observed for satP gene deletion strain. The mouse infection model confirmed that mice infected with satP gene deletion strains were more likely to be treated with ENR than mice infected with wild-type bovine PM strains. The results show that satP has potential to be a target of fluoroquinolone resistance inhibitors.

Subject Areas

Bovine respiratory disease; Pasteurella multocida; resistance; tolerance; satP.

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