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

Authors: Ma, Hao; Tatum, Fred; BRIGGS, ROBERT - Retired ARS Employee; Dassanayake, Rohana; KENDRICK, TASIA - Michigan State University; Casas, Eduardo

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/20/2026
Publication Date: 1/30/2026
Citation: Ma, H., Tatum, F.M., Briggs, R.E., Dassanayake, R.P., Kendrick, T.M., Casas, E. 2026. Transcriptome profiling indicates varied gene responses to Pasteurella multocida mutant infections in cattle. PLOS ONE. 21(1). Article e0341813. https://doi.org/10.1371/journal.pone.0341813.
DOI: https://doi.org/10.1371/journal.pone.0341813

Interpretive Summary: Pasteurella multocida is one of the pathogens causing bovine respiratory disease, and the development of an effective vaccine is important to improve animal health and welfare. The objective of this study was to evaluate the expression of genes in cattle, produced by three different potential vaccine candidates. These vaccine candidates were made by disrupting one of the three genes that produce virulence factors in P. multocida. Animals in different groups were given the three vaccine candidates, another group was left as a control, and yet another group was given P. multocida to produce an immune response. Later, all groups were given P. multocida to develop respiratory disease. Tissues were collected after the experiment and RNA was extracted and sequenced. After evaluating the profiles of gene expression in blood and liver, animals inoculated with one of the vaccine candidates had fewer lesions and caused fewer changes in the expression of genes. The modified P. multocida identified could likely be used as a vaccine candidate.

Technical Abstract: Pasteurella multocida is one of the pathogens causing bovine respiratory disease, and the development of an effective vaccine is important to improve animal health and welfare. Live-attenuated vaccines can create a strong and long-lasting immune response with minimal side effects. The objective of this study was to evaluate potential live vaccine candidates from P. multocida mutants (fhaB2, hyaE, and nanP) produced by disruption one of the three genes encoding putative virulence factors (fhaB2: filamentous haemagglutinin 2; hyaE: hyaluronic acid capsule; nanP: sialic acid uptake) of a serogroup 3 strain (P-1062, WT) by clinical test and transcriptome analysis. Challenge with WT, the 3 mutants conferred protection against P. multocida, leading to decreased 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 blood and 6473 DETs in liver when comparing the sham, WT, and each of the mutants. A total of 15 and 64 differentially expressed microRNAs (DEmiRNAs) and 12 and 74 differentially expressed long non-coding RNAs (DElncRNAs) were found in blood and liver respectively. The DEmiRNA and DElncRNA were associated with some of the DETs. The greatest number of unique DETs were found between hyaE vs sham in liver, which agreed with its 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 liver for the DETs identified by WT vs sham, nanP vs sham, and hyaE vs sham respectively, and were related to signaling pathway, stimulus, and sensory perceptions in biological process with the molecular function of olfactory receptor activity. The number of identified DETs, the decreased percentage of lung lesions, and colonization rates indicate that fhaB could be a promising vaccine candidate.