![]() ![]() The bacterial cell membrane is a highly selective permeable barrier. The variation of DNA gyrase or topoisomerase VI is the main cause of bacterial resistance to fluoroquinolones. Our previous results indicated that Pm is extremely resistant to fluoroquinolones in vivo and in vitro, and the mechanism is mainly mediated through target mutation in gyrA and parC. Detection of QRDR gene mutation has been a hot issue in the early study of fluoroquinolone resistance. For example, they correspond to Gly–Asp94 in Mycobacterium tuberculosis, Ala67–Gln106 in Escherichia coli and Arg88Ile in Pm. The specific positions of proteins encoded by this region are different across different strains. Mutation in this region can cause drug resistance. Within the gyrA gene, quinolone-resistant determining region (QRDR) is closely associated with drug resistance. In Pm, gyrA gene mutation often leads to the structural change of DNA helicase, which leads to drug resistance. Mutation of any of these four proteins may cause drug resistance to fluoroquinolones. DNA gyrase is a tetramer composed of GyrA and GyrB proteins, and topoisomerase VI is a tetramer composed of ParC and ParE proteins. Among them, variation of DNA gyrase or topoisomerase IV, bacterial cell membrane permeability and bacterial active efflux mechanisms are the most common. Unfortunately, Pm has recently been reported to possess acquired fluoroquinolone resistance mechanisms. Enrofloxacin has a good therapeutic effect on nasal, upper respiratory and lung infections caused by Pm infection in animals. Therefore, this study found that the satP gene was related to the tolerance and pathogenicity of Pm, and may be used as a target of enrofloxacin synergistic effect.įluoroquinolones are one of the main therapeutic drugs for Pm infections in animals. The pathogenicity of ΔPm and Pm was measured by an acute pathogenicity test in mice, and it was found that the pathogenicity of ΔPm was reduced by about 400 times. MDK 99, agar diffusion and mutation frequency experiments showed significantly lower tolerance of ΔPm than the wild-type strains. Through a continuously induced resistance test, it was found that the resistance rate of ΔPm was obviously lower than that of Pm in vitro. In order to further confirm the function of this gene, we constructed a satP deletion ( ΔPm) strain using suicide vector plasmid pRE112, and constructed the C-Pm strain using pBBR1-MCS, and further analyzed the function of the satP gene. The satP gene, of which the expression changed significantly with the increase in drug resistance, was screened. Then transcriptome sequencing of clinically isolated sensitive strains, resistant and highly drug-resistant strains, treated with enrofloxacin at sub-inhibitory concentrations, were performed. In order to better understand the resistance mechanism of Pm to enrofloxacin, we isolated PmS and PmR strains with the same PFGE typing in vitro, and artificially induced PmR to obtain the highly resistant phenotype, PmHR. ![]() Our earlier research group found that with clinical use of enrofloxacin, Pm was more likely to develop drug resistance to enrofloxacin. Pasteurella multocida (Pm) is one of the major pathogens of bovine respiratory disease (BRD), which can develop drug resistance to many of the commonly used antibiotics. We found that the satP gene is related to the tolerance and pathogenicity of Pasteurella multocida, and can be used as a target of enrofloxacin synergistic effect. After satP gene deletion, the resistance of Pasteurella multocida was obviously lower than that of wild-type strains in vitro, and the pathogenicity of Pasteurella multocida was reduced by about 400 times. In order to further confirm the function of this gene, we constructed the deleted and complemented strains of satP, and further analyzed the function of the satP gene. Then, transcriptome sequencing of clinically isolated sensitive strains, resistant and highly drug-resistant strains, treated with enrofloxacin at sub-inhibitory concentrations, were performed. In order to better understand the resistance mechanism of Pasteurella multocida to enrofloxacin, we isolated PmS and PmR strains with the same PFGE typing in vitro, and artificially induced PmR to obtain the highly resistant phenotype, PmHR. We found that enrofloxacin has shown a high drug resistance in clinical treatment of Pasteurella multocida infection. Pasteurella multocida is a major pathogen of bovine respiratory disease, which is resistant to many of the commonly used antibiotics.
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