Experimental pathogenicity and comparative genome analysis of high- and low-virulence strains of rabbit-origin Pasteurella multocida

Pasteurella multocida, the causative pathogen of rabbit pasteurellosis, causes significant economic losses in the commercial rabbit industry. However, the associated pathogenic mechanism of P. multocida remains unclear. The aim of this study is to compare the genomes and pathogenicity of high- and low-virulence strains of P. multocida to advance the current understanding of rabbit pasteurellosis. The high-virulence strain rapidly proliferates in the lung and spleen of infected mice within approximately 9 h, maintaining a high bacterial load until host death. Meanwhile, the low-virulence strain only proliferates in mouse organs for a short time, with the bacterial load beginning to decrease 13 h post-infection. Moreover, the expressions of inflammatory cytokines MCP-1, TNF-α, and IL-1β are upregulated in all infected mouse lung and spleen tissue, however, the high-virulence strain induced significantly higher expression than the low-virulence strain. Histopathological analysis revealed greater inflammation and tissue lesions in the lung and spleen of mice infected with the high-virulence strain. Two pathogenicity-associated regions unique to the genome of the high-virulence strain harbor approximately 199 genes, including functional genes related to virulence factors, such as lipopolysaccharide biosynthesis, iron acquisition, biosynthesis of outer membrane proteins, and adhesion. These two genomic regions are shared by three previously sequenced, highly virulent P. multocida strains in rabbits. In conclusion, the increased pathogenicity of high-virulence P. multocida may be due to the presence of virulence-associated genes in two unique genomic regions, resulting in strong proliferative activity, significant inflammation, and pathological lesions in the mouse model. These findings provide important insights regarding the pathogenic mechanism underlying rabbit pasteurellosis.