L-Ascorbic Acid Shapes Bovine Pasteurella multocida Serogroup A Infection

Abstract

Bovine Pasteurella multocida serogroup A (bovine PmA) is one of the most important pathogens causing fatal pneumonia in cattle. However, it is largely unknown how nutrition shapes bovine PmA infection. Here, we discovered that the infected lung held the highest bacterial density than other tissues during infection. By screening the different metabolites between high (lung)- and low (liver)-bacterial density tissues, the present work revealed that L-ascorbic acid and L-aspartic acid directly influenced bovine P. multocida growth. Interestingly, L-ascorbic acid, which is expressed at higher levels in the infected livers, inhibited bovine PmA growth as well as virulence factor expression and promoted macrophage bactericidal activity in vitro. In addition, ascorbic acid synthesis was repressed upon bovine PmA infection, and supplementation with exogenous L-ascorbic acid significantly reduced the bacterial burden of the infected lungs and mouse mortality. Collectively, our study has profiled the metabolite difference of the murine lung and liver during bovine PmA infection. The screened L-ascorbic acid showed repression of bovine PmA growth and virulence expression in vitro and supplementation could significantly increase the survival rate of mice and reduce the bacterial load in vivo, which implied that L-ascorbic acid could serve as a potential protective agent for bovine PmA infection in clinic.

Pasteurella multocida activates apoptosis via the FAK-AKT-FOXO1 axis to cause pulmonary integrity loss, bacteremia, and eventually a cytokine storm

“…In our previous work [ 21 ], we found that mice intranasally infected with PmCQ2 exhibited severe lung damage and extrapulmonary infections. Here, we repeated previous work and found that intranasal infection with 1 × 10 4 CFU of lethal PmCQ2 indeed induced serious lung damage in mice in a time-dependent manner (Figures 1 A through C ).…”

“…As a respiratory pathogen, P. multocida infection, particularly capsular type A infection, frequently causes clinically detectable pulmonary damage [ 18 ]. Nevertheless, there is a growing body of evidence indicating that P. multocida , including capsular type A, can both damage the host's respiratory system and leak into its blood circulation system (bacteremia), leading to extrapulmonary infections [ 19 – 21 ]. Notably, P. multocida bacteremia and P. multocida -induced extrapulmonary damage have become increasingly common in the clinic, suggesting that P. multocida -induced systemic infection could be an important part of its pathogenesis [ 22 – 24 ].…”

Pasteurella multocida activates Rassf1-Hippo-Yap pathway to induce pulmonary epithelial apoptosis

“…Pm can be classified into 5 serotypes, based on their capsule characteristics: A, B, D, E and F [5]. Among these, Pm serogroup A (PmA), which is usually found in domestic animals, especially in cattle, rabbits and chickens, is known to cause fatal pneumonia, resulting in significant economic losses in animal husbandry worldwide [6][7][8][9][10].…”

Immune Protective Efficacy of China’s Traditional Inactivated and Attenuated Vaccines against the Prevalent Strains of Pasteurella multocida in Mice

“…This bacterium was named after Louis Pasteur, who first recognized P. multocida as the causative agent of fowl disease in 1880 [1]. P. multocida is a widespread pathogen capable of infecting a wide variety of animals [2][3][4] and an opportunistic pathogen of humans. It is the primary causative agent of fowl cholera in chickens [5], hemorrhagic septicemia in ungulates, snuffles in rabbits [6], and progressive atrophic rhinitis or pneumonia in pigs [7].…”