Abstract
Pasteurella multocida is one of the primary pathogens of bovine respiratory disease (BRD), and causes huge losses in the cattle industry. The Pm3 strain was a natural isolate, which is a strong form of pathogen and is sensitive to fluoroquinolones antibiotics. A high fluoroquinolone resistant strain, Pm64 (MIC = 64 μg/mL), was formed after continuous induction with subinhibitory concentration (1/2 MIC) of enrofloxacin, with the enhanced growth characteristics and large attenuation of pathogenicity in mice. This study reports the whole genome sequence and the transcription profile by RNA-Seq of strain Pm3/Pm64. The results showed an ineffective difference between the two strains at the genome level. However, 32 genes could be recognized in the gene islands (GIs) of Pm64, in which 24 genes were added and 8 genes were lost. Those genes are involved in DNA binding, trehalose metabolism, material transportation, capsule synthesis, prophage, amino acid metabolism, and other functions. In Pm3 strain, 558 up-regulated and 568 down-regulated genes were found compared to Pm64 strain, from which 20 virulence factor-related differentially expressed genes (DEGs) were screened. Mainly differentially transcribed genes were associated with capsular polysaccharide (CPS), lipopolysaccharide (LPS), lipooligosaccharide (LOS). Iron utilization, and biofilm composition. We speculated that the main mechanism of virulence attenuation after the formation of resistance of Pm64 comes from the change of the expression profile of these genes. This report elucidated the toxicity targets of P. multocida serogroup A which provide fundamental information toward the understanding of the pathogenic mechanism and to decreasing antimicrobial drugs resistance.
Highlights
In recent years, the high incidence of bovine respiratory diseases (BRD) has seriously affected the cattle breeding industry worldwide, and these diseases mainly occur in fattening cattle and calves during long distance transportation, and cause a lack of energy and appetite, accompanied by cough, runny nose, and dyspnea [1]
Several researchers confirmed that P. multocida serogroup A was the primary pathogen causing BRD in China, and in our previous study, we found it has a higher risk of fluoroquinolone resistance during antibiotic therapy [6, 7]
Observing the pathological changes under a microscope, it can be seen that the alveolar wall capillaries are dilated; a large number of neutrophils infiltrate, which is consistent with the infection characteristics of P. multocida (Supplementary Figure 1)
Summary
The high incidence of bovine respiratory diseases (BRD) has seriously affected the cattle breeding industry worldwide, and these diseases mainly occur in fattening cattle and calves during long distance transportation, and cause a lack of energy and appetite, accompanied by cough, runny nose, and dyspnea [1]. In North America, BRD accounts for ∼75% of all disease incidence and 50% of all mortality in cattle farms, with an even higher prevalence (nearly 90%) in calves [2]. Bacterial pathogens which are associated with BRD include Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni [3]. Among these bacteria, Pasteurella multocida (P. multocida), a pathogenic gram-negative bacterium, has been divided into three subspecies, five capsular serogroups, and 16 serotypes. Several researchers confirmed that P. multocida serogroup A was the primary pathogen causing BRD in China, and in our previous study, we found it has a higher risk of fluoroquinolone resistance during antibiotic therapy [6, 7]
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