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

Area of Science:

• Veterinary immunology and vaccinology
• Bacterial pathogenesis and host-pathogen interactions
• Transcriptomics and molecular biology in animal health

Background:

• Bovine respiratory disease (BRD) significantly impacts cattle health and productivity, necessitating effective control strategies.
• Live-attenuated vaccines offer a promising approach for inducing robust, long-lasting immunity against BRD with minimal adverse effects.
• Pasteurella multocida is a key pathogen in BRD, making vaccine development crucial for animal welfare and economic reasons.

Purpose of the Study:

• To evaluate three Pasteurella multocida mutants (fhaB2, hyaE, nanP) as potential live vaccine candidates against BRD.
• To assess the protective efficacy of these mutants through clinical challenge studies and transcriptome analysis.
• To identify molecular mechanisms underlying host response and vaccine efficacy using transcriptomic data.

Main Methods:

• Generation of three P. multocida mutants by disrupting fhaB2, hyaE, and nanP genes in a serogroup 3 strain (P1062).
• Clinical evaluation of mutant efficacy through challenge studies, assessing lung lesions and colonization rates.
• Transcriptome analysis of blood and liver tissues to identify differentially expressed protein-coding transcripts (DETs), microRNAs (DEmiRNAs), and long non-coding RNAs (DElncRNAs).

Main Results:

• All three P. multocida mutants conferred protection against challenge, significantly reducing lung lesions (4.7-6.2%) compared to the sham group (22.4%).
• Transcriptome analysis revealed substantial numbers of DETs in blood (807) and liver (6473), along with differentially expressed non-coding RNAs.
• The fhaB2 mutant demonstrated promising vaccine potential, indicated by reduced lung lesions and colonization, supported by transcriptomic data showing distinct host responses.

Conclusions:

• The fhaB2, hyaE, and nanP mutants of P. multocida provide protection against BRD challenge in cattle.
• Transcriptome analysis provides insights into host responses to vaccination and infection, highlighting pathways related to signaling and sensory perception.
• The fhaB2 mutant is identified as a promising candidate for a live-attenuated vaccine against bovine respiratory disease due to its efficacy and favorable transcriptomic profile.