## 1 Introduction  
_Pasteurella multocida (Pm)_ is a Gram-negative bacterium implicated in multi-host infections. Strains of their species are currently classified into type A, type B, type D, type E and type F serogroups [1; 2]. _Pm_ is one of the primary pathogens of bovine respiratory disease (BRD) in Asia, Middle East, Africa and Europe [3; 4; 5]. At present, the infection of cattle with _Pm_ leads to tremendous economic losses for the cattle industry due to increased mortalities and high treatment costs [6]. The treatment of BRD mainly depends on antibiotics, and penicillin has often been used as the drug of choice for the last few decades [7; 8]. However, due to the irrational use of antibiotics in clinical treatment, it has been observed that the drug resistance rate of \(\beta\)-lactams, macrolides and tetracyclines has increased in recent years [9; 10; 11; 12]. Irrational use of antibiotics to prevent the threat of BRD increases the rate of _Pm_ resistance [13]. Fluoroquinolones are one of the main therapeutic drugs for _Pm_ infections in animals [12]. Enrofloxacin has a good therapeutic effect on nasal, upper respiratory and lung infections caused by _Pm_ infection in animals [14; 15; 16]. Unfortunately, _Pm_ has recently been reported to possess acquired fluoroquinolone resistance mechanisms [17]. Among them, variation of DNA gyrase or topoisomerase IV, bacterial cell membrane permeability and bacterial active efflux mechanisms are the most common. DNA gyrase is a tetramer composed of GyrA and GyrB proteins, and topoisomerase VI is a tetramer composed of ParC and ParE proteins [18]. Mutation of any of these four proteins may cause drug resistance to fluoroquinolones. In _Pm_, _gyrA_ gene mutation often leads to the structural change of DNA helicase, which leads to drug resistance. Within the _gyrA_ gene, quinolone-resistant determining region (QRDR) is closely associated with drug resistance [19]. Mutation in this region can cause drug resistance. The specific positions of proteins encoded by this region are different across different strains. For example, they correspond to Gly-Asp94 in _Mycobacterium tuberculosis_, Ala67-Gln106 in _Escherichia coli_ and Arg88 Ile in _Pm_. Detection of QRDR gene mutation has been a hot issue in the early study of fluoroquinolone resistance [20]. 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_[21]. The variation of DNA gyrase or topoisomerase VI is the main cause of bacterial resistance to fluoroquinolones. The bacterial cell membrane is a highly selective permeable barrier. There are some special proteins in the outer membrane of bacteria, which are called outer membrane proteins (OMPs). OMPs account for about half of the cell wall in Gram-negative bacteria. The OMPs have the functions of antibiotic, iron transport, host adhesion and maintenance of membrane integrity [22]. At present, it is clear that OmpF, ToIC and OmpX are related to fluoroquinolone resistance [23]. Simultaneously, there is an energy-dependent protein efflux pump in the inner membrane of _Pm_ which can discharge drugs, resulting in drug resistance [24]. The efflux of fluoroquinolones in _Pm_ is mainly related to the survival-modulation-cell division (RND) family, which includes the transporters of calcium, cobalt and nickel [25]. Among Gram-negative bacteria, the AcrAB-ToIC system is the main active efflux pump related to fluoroquinolones. The active efflux pump and the change of bacterial outer membrane permeability play an important role in multidrug resistance, and attention has been paid to this by researchers [26]. However, the development of antimicrobial resistance is a complicated multifactorial process, and related studies have shown that the formation of drug resistance also depends on tolerance factors [27; 28].