Transcriptome profiling indicates varied gene responses to Pasteurella multocida mutant infections in cattle

Pasteurella multocida is a pathogen that causes bovine respiratory disease, and the development of an effective vaccine is important for improving animal health. Live-attenuated vaccines induce a long-lasting immune response with minimal side effects. The objective of this study was to evaluate potential live vaccine candidates from three P. multocida mutants produced by separately disrupting the genes of filamentous hemagglutinin 2 (fhaB2), hydrogenase-1 operon (hyaE), and n-acylneuraminate-9-phosphatase (nanP) of a serogroup 3 strain (P1062, WT) by clinical testing and transcriptome analysis. Challenge with WT and the three mutants conferred protection against P. multocida, with less lung lesions (4.7-6.2%) compared to 22.4% in the sham group. Transcriptome analysis identified 807 differentially expressed protein-coding transcripts (DETs) in the blood and 6473 DETs in the liver compared to the sham, WT, and each of the mutants. In total, 15 and 64 differentially expressed microRNAs (DEmiRNAs) and 12 and 74 differentially expressed long non-coding RNAs (DElncRNAs) were identified in blood and liver, respectively. The DEmiRNAs were not significantly associated with the DETs within each comparison. DElncRNAs were associated with 12 and 170 DETs in blood and liver respectively. The greatest number of unique DETs were found between hyaE and sham groups in the liver, which agreed with the low colonization rate in the nares and palatine tonsils. For the DETs between sham and WT the under-enriched gene ontology terms in blood were all included in the liver for the DETs identified by WT vs. sham, nanP vs. sham, and hyaE vs. sham, and were related to the signaling pathway, stimulus, and sensory perceptions in biological processes with the molecular function of olfactory receptor activity. The number of identified DETs, decreased percentage of lung lesions, and colonization rates indicate that fhaB2 could be a promising vaccine candidate.