Abstract

Pasteurella multocida is a gram-negative opportunistic pathogen that causes various diseases in poultry, livestock, and humans, resulting in huge economic losses. Pasteurella multocida serotype A CQ6 (PmCQ6) is a naturally occurring attenuated strain, while P. multocida serotype A strain CQ2 (PmCQ2) is a highly virulent strain isolated from calves. Compared with PmCQ2, it was found that bacterial loads and tissue lesions of lung tissue significantly decreased and survival rates significantly improved in mice infected with PmCQ6 by intranasal infection. However, comparative genome analysis showed that the similarity between the two strains is more than 99%. To further explore the virulence difference mechanism of PmCQ2 and PmCQ6, transcriptome sequencing analysis of the two strains was performed. The RNA sequencing analysis of PmCQ2 and PmCQ6 showed a large number of virulence-related differentially expressed genes (DEGs) in vivo and in vitro. Among them, 38 virulence-related DGEs were significantly up-regulated due to PmCQ6 infection, while the number of PmCQ2 infection was 46, much more than PmCQ6. In addition, 18 virulence-related DEGs (capsule, iron utilization, lipopolysaccharide, and outer membrane protein-related genes) were up-regulated in PmCQ2 infection compared to PmCQ6 infection, exhibiting a higher intensive expression level in vivo. Our findings indicate that these virulence-related DEGs (especially capsule) might be responsible for the virulence of PmCQ2 and PmCQ6, providing prospective candidates for further studies on pathogenesis.

Highlights

  • Pasteurella multocida is a gram-negative bacterium well-known for causing diseases in a wide range of birds and mammals [1], including fowl cholera, swine atrophic rhinitis, rabbit septicemia, bovine pneumonia, and human wound abscesses/meningitis following cat/dog-inflicted injuries [2,3,4,5], which lead to huge economic losses to animal husbandry worldwide

  • Compared with the Pasteurella multocida serotype A CQ6 (PmCQ6)-infected group, the lung tissue lesions in the PmCQ2infected group showed a significant increase based on hematoxylin and eosin (H&E) staining (Figures 1C–E)

  • In this study, a mouse model of P. multocida pneumonia caused by PmCQ2 (1 × 108 colony-forming units (CFU)) and PmCQ6 (1 × 108 CFU) was established via intranasal infection

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Summary

Introduction

Pasteurella multocida is a gram-negative bacterium well-known for causing diseases in a wide range of birds and mammals (e.g., humans and economically important animal species) [1], including fowl cholera, swine atrophic rhinitis, rabbit septicemia, bovine pneumonia, and human wound abscesses/meningitis following cat/dog-inflicted injuries [2,3,4,5], which lead to huge economic losses to animal husbandry worldwide. Pasteurella multocida have been classified into five serotypes (A, B, D, E, and F) according to the specificity of capsular antigens [6, 7] and 16 Heddleston serotypes based on the lipopolysaccharide (LPS) antigens [8]. The capsular type A P. multocida mainly causes pneumonia and serious bovine respiratory diseases. Pasteurella multocida possesses a number of virulence factors, mainly including capsular polysaccharide, iron utilizationrelated genes, LPS, and outer membrane proteins (OMPs) [4, 9, 10]. It is well-known that the virulence factors expressed by P. multocida play key roles in pathogenesis [11,12,13]. The virulence of P. multocida acapsular mutants was strongly attenuated in mice [14]; the galE (UDP-galactose) mutant for P. multocida LPS biosynthesis was completely attenuated in mice [15]

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