The role of lipooligosaccharide phosphorylcholine in colonization and pathogenesis of Histophilus somni in cattle

Abstract

Histophilus somni is a Gram-negative bacterium and member of the Pasteurellaceae that is responsible for respiratory disease and other systemic infections in cattle. One of the bacterium’s virulence factors is antigenic phase variation of its lipooligosaccharide (LOS). LOS antigenic variation may occur through variation in composition or structure of glycoses or their substitutions, such as phosphorylcholine (ChoP). However, the role of ChoP in the pathogenesis of H. somni disease has not been established. In Haemophilus influenzae ChoP on the LOS binds to platelet activating factor on epithelial cells, promoting bacterial colonization of the host upper respiratory tract. However, ChoP is not expressed in the blood as it also binds C-reactive protein, resulting in complement activation and killing of the bacteria. In order to simulate the susceptibility of calves with suppressed immunity due to stress or previous infection, calves were challenged with bovine herpes virus-1 or dexamethazone 3 days prior to challenge with H. somni. Following challenge, expression of ChoP on the LOS of 2 different H. somni strains was associated with colonization of the upper respiratory tract. In contrast, lack of ChoP expression was associated with bacteria recovered from systemic sites. Histopathology of cardiac tissue from myocarditis revealed lesions containing bacterial clusters that appeared similar to a biofilm. Furthermore, some respiratory cultures contained substantial numbers of Pasteurella multocida, which were not present on preculture screens. Subsequent biofilm experiments have shown that H. somni and P. multocida grow equally well together in a biofilm, suggesting a commensal relationship may exist between the two species. Our results also showed that ChoP contributed to, but was not required for, adhesion to respiratory epithelial cells. In conclusion, expression of ChoP on H. somni LOS contributed to colonization of the bacteria to the host upper respiratory tract, but phase variable loss of ChoP expression may help the bacteria survive systemically.

Microbial Modulation of Host Immunity with the Small Molecule Phosphorylcholine

“…S. pneumoniae strains without ChoP-modified TA are unable to colonize the upper respiratory tract in mice and are less virulent in a murine sepsis model (49). ChoP expression in Histophilus somni has also been shown to increase colonization of its bovine host (50).…”

Identification of thelic1ABCDoperon that controls the phase-variable expression of phosphorylcholine on lipopolysaccharide fromAvibacterium paragallinarum

“…Three of the 40 re-isolates of TW07 had variation in the number of repeats and the frequency of variation was 7.5%. This high frequency may have resulted from immune selection since switching off ChoP expression enhanced the systematic survival of bacteria (Humphries & High, 2002;Elswaifi et al, 2012). Taken together, data presented here showed that Av.…”

“…Many mucosal pathogens, including H. influenzae, have evolved a mechanism for phase-variable (ON/OFF switching) expression of ChoP (Weiser et al, 1997;Warren & Jennings, 2003). It is proposed that switching ON expression of ChoP helps bacteria to colonize on the mucosal surface during the initial stage of infection, whereas switching OFF helps bacteria to escape serum killing mediated by C-reactive protein during systematic infection (Humphries & High, 2002;Elswaifi et al, 2012).…”

Detection of Antibodies to the Biofilm Exopolysaccharide of Histophilus somni following Infection in Cattle by Enzyme-Linked Immunosorbent Assay

“…The prechallenge with virus or dexamethasone was used to stress the animals and suppress the innate immune response. Without prior prechallenge, the animals become colonized but do not develop disease (13). These prechallenged stressed animals developed clinical symptoms of pneumonia.…”

“…A postmortem examination revealed that the calves had various degrees of purulent bronchopneumonia with abscesses and multifocal purulent myocarditis. A more complete description of the pathology of each calf has been provided elsewhere (13). Normal respiratory tract bacteria, such as viridans group streptococci, were not isolated from the bronchoalveolar lavage fluid specimens, indicating that the H. somni isolates recovered from BAL fluid were not part of the normal upper respiratory tract flora.…”