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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #423056
Research Project: Host-pathogen Interactions and Control Strategies for Bacterial Respiratory Pathogens in Cattle

Location: Ruminant Diseases and Immunology Research

Title: Mannheimia haemolytica isogenic capsular and LPS-sialylation gene deletion mutants are attenuated in a calf lung challenge model

Author
item MENGHWAR, HARISH - Oak Ridge Institute For Science And Education (ORISE)
item Tatum, Fred
item Briggs, Robert
item Zakrzewicz, Anna
item Chriswell, Bradley
item Kanipe, Carly
item Ma, Hao
item Casas, Eduardo
item Dassanayake, Rohana

Submitted to: Microbiology Spectrum
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/13/2025
Publication Date: 4/23/2025
Citation: Menghwar, H., Tatum, F.M., Briggs, R.E., Zakrzewicz, A.K., Chriswell, B.O., Kanipe, C.R., Ma, H., Casas, E., Dassanayake, R.P. 2025. Mannheimia haemolytica isogenic capsular and LPS-sialylation gene deletion mutants are attenuated in a calf lung challenge model. Microbiology Spectrum. Article e00283-25. https://doi.org/10.1128/spectrum.00283-25.
DOI: https://doi.org/10.1128/spectrum.00283-25

Interpretive Summary: Mannheimia haemolytica is an economically important bacterial pathogen to the US cattle industry and the leading bacterial cause of the development of bovine respiratory disease complex. Sialic acid and capsule have been identified as important virulence determinants (in M. haemolytica). However, no animal studies have been conducted to determine their roles in the virulence. To fill this knowledge gap, we conducted a calf lung challenge study to assess their roles in pneumonia development. We found that the sialic acid and capsular mutants caused significantly less lung lesions and recovered fewer bacterial loads as compared to parent wildtype strain challenged calves. These findings suggest that sialic acid and capsule are important virulence factors for the survival of M. haemolytica within the host.

Technical Abstract: Bovine respiratory disease complex (BRDC) is a multifactorial syndrome that involves complex interactions between environment, bacterial/viral pathogens, and the host. Mannheimia haemolytica is the most significant bacterial pathogen associated with BRDC. This study investigated the virulence of an M. haemolytica serotype (St)1 capsular ('cap) mutant and an M. haemolytica LPS-sialylation ('neuA, CMP-sialic acid synthetase) mutant in a calf lung challenge model. Twelve colostrum-deprived calves were divided into three groups (four calves/group), and intratracheally administered inoculum of M. haemolytica wildtype (WT), or M. haemolytica 'cap, or M. haemolytica 'neuA strains (~5 × 108 CFU/animal). Animals were observed for signs of pneumonia and were humanely euthanized two-to-three days post-bacterial challenge. Lungs were examined for gross pulmonary lesions, histopathological changes, and bacterial culture. Calves administered WT M. haemolytica exhibited severe lung lesions characterized by extensive consolidation and hemorrhage. In contrast, calves administered M. haemolytica 'cap, or M. haemolytica 'neuA mutants displayed significantly reduced lung lesions (P < 0.05). The most severely affected lung lobes were the right cranial and right middle lobes, with ~50% consolidation. The WT group exhibited significantly higher lung tissue bacterial loads than either of the groups receiving the mutant strains (P < 0.05). The reduced clinical signs, pneumonic lung lesions, and bacterial recovery in the lungs of the calves challenged with either the 'cap or the 'neuA M. haemolytica mutant strains indicated that these mutations were significantly less virulent than the parent strain.