Characterization of Histophilus somni sialic acid uptake mutant (ΔnanP-ΔnanU) using a mouse septicemia and mortality model

Menghwar, Harish; Tatum, Fred M.; Briggs, Robert E.; Kanipe, Carly; Casas, Eduardo; Kaptur, Jean; Kaplan, Bryan S.; Inzana, Thomas J.; Azadi, Parastoo; Dassanayake, Rohana P.

doi:10.1016/j.micpath.2024.106839

Characterization of Histophilus somni sialic acid uptake mutant (ΔnanP-ΔnanU) using a mouse septicemia and mortality model

Journal Article · Sat Aug 03 00:00:00 EDT 2024 · Microbial Pathogenesis

DOI:https://doi.org/10.1016/j.micpath.2024.106839· OSTI ID:2530507

^[1]; Tatum, Fred M. ^[2]; Briggs, Robert E. ^[2]; ^[2]; Casas, Eduardo ^[2]; Kaptur, Jean ^[2]; ^[2]; Inzana, Thomas J. ^[3]; ^[4]; ^[2]

United States Department of Agriculture, Ames, IA (United States); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
United States Department of Agriculture, Ames, IA (United States)
Long Island University, Brookville, NY (United States)
University of Georgia, Athens, GA (United States)

Histophilus somni is an important pathogen of the bovine respiratory disease complex, yet the mechanisms underlying its virulence remain poorly understood. It is known that H. somni can incorporate sialic acid into lipooligosaccharide (LOS), and sialylated H. somni is more resistant to phagocytosis and complement-mediated killing by serum compared to non-sialylated bacteria in vitro. However, the virulence of non-sialylated H. somni has not been evaluated in vivo using an animal model. In this study, we investigated the contribution of sialic acid to virulence by constructing an H. somni sialic acid uptake mutant (ΔnanP-ΔnanU) and comparing the parent and mutant strains in a mouse septicemia and mortality model. Intraperitoneal challenge of mice with wildtype H. somni (1 × 10⁸ colony forming units/mouse, CFU) was lethal to all animals. Mice challenged with three different doses (1, 2, or 5 × 108 CFU/mouse) of an H. somni ΔnanP-ΔnanU sialic acid uptake mutant exhibited survival rates of 90 %, 60 %, and 0 % respectively. High-performance anion exchange chromatography analyses revealed that LOS prepared from both parent and the ΔnanP-ΔnanU mutant strains of H. somni were sialylated. These findings suggest the presence of de novo sialic acid synthesis pathway, although the genes associated with de novo sialic acid synthesis (neuB and neuC) were not identified by genomic analysis. The lower attenuation in mice is most likely attributed to the sialylated LOS of H. somni nanPU mutant.

View Accepted Manuscript (DOE)

Research Organization:: University of Georgia, Athens, GA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0015662

OSTI ID:: 2530507

Journal Information:: Microbial Pathogenesis, Journal Name: Microbial Pathogenesis Vol. 194; ISSN 0882-4010

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Bovine respiratory disease complex
Histophilus somni
Mouse model
Sialic acid uptake mutant
Virulence

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References (23)

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