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Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus

Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus
Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus

The Gram-negative anaerobic bacterium Dichelobacter nodosus (Dn) causes footrot in ruminants, a debilitating and highly contagious disease that results in necrotic hooves and significant economic losses in agriculture. Vaccination with crude whole-cell vaccine mixed with multiple recombinant fimbrial proteins can provide protection during species-specific outbreaks, but subunit vaccines containing broadly cross-protective antigens are desirable. We have investigated two D. nodosus candidate vaccine antigens. Macrophage Infectivity Potentiator Dn-MIP (DNO_0012, DNO_RS00050) and Adhesin Complex Protein Dn-ACP (DNO_0725, DNO_RS06795) are highly conserved amongst ~170 D. nodosus isolates in the https://pubmlst.org/dnodosus/ database. We describe the presence of two homologous ACP domains in Dn-ACP with potent C-type lysozyme inhibitor function, and homology of Dn-MIP to other putative cell-surface and membrane-anchored MIP virulence factors. Immunization of mice with recombinant proteins with a variety of adjuvants induced antibodies that recognised both proteins in D. nodosus. Notably, immunization with fimbrial-whole-cell Footvax vaccine induced anti-Dn-ACP and anti-Dn-MIP antibodies. Although all adjuvants induced high titre antibody responses, only antisera to rDn-ACP-QuilA and rDn-ACP-Al(OH)3 significantly prevented rDn-ACP protein from inhibiting lysozyme activity in vitro. Therefore, a vaccine incorporating rDn-ACP in particular could contribute to protection by enabling normal innate immune lysozyme function to aid bacterial clearance.

2045-2322
1-14
Humbert, Maria Victoria
82134d25-24b8-4fdd-bd1c-461683b5322e
Jackson, Alexandra
eb2e2dd5-0d2c-47af-89a9-09b82f4b4ccb
Orr, Christian M.
f64259af-4120-481a-8e12-11344d005de0
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Humbert, Maria Victoria
82134d25-24b8-4fdd-bd1c-461683b5322e
Jackson, Alexandra
eb2e2dd5-0d2c-47af-89a9-09b82f4b4ccb
Orr, Christian M.
f64259af-4120-481a-8e12-11344d005de0
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078

Humbert, Maria Victoria, Jackson, Alexandra, Orr, Christian M., Tews, Ivo and Christodoulides, Myron (2019) Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus. Scientific Reports, 9 (1), 1-14. (doi:10.1038/s41598-019-46506-z).

Record type: Article

Abstract

The Gram-negative anaerobic bacterium Dichelobacter nodosus (Dn) causes footrot in ruminants, a debilitating and highly contagious disease that results in necrotic hooves and significant economic losses in agriculture. Vaccination with crude whole-cell vaccine mixed with multiple recombinant fimbrial proteins can provide protection during species-specific outbreaks, but subunit vaccines containing broadly cross-protective antigens are desirable. We have investigated two D. nodosus candidate vaccine antigens. Macrophage Infectivity Potentiator Dn-MIP (DNO_0012, DNO_RS00050) and Adhesin Complex Protein Dn-ACP (DNO_0725, DNO_RS06795) are highly conserved amongst ~170 D. nodosus isolates in the https://pubmlst.org/dnodosus/ database. We describe the presence of two homologous ACP domains in Dn-ACP with potent C-type lysozyme inhibitor function, and homology of Dn-MIP to other putative cell-surface and membrane-anchored MIP virulence factors. Immunization of mice with recombinant proteins with a variety of adjuvants induced antibodies that recognised both proteins in D. nodosus. Notably, immunization with fimbrial-whole-cell Footvax vaccine induced anti-Dn-ACP and anti-Dn-MIP antibodies. Although all adjuvants induced high titre antibody responses, only antisera to rDn-ACP-QuilA and rDn-ACP-Al(OH)3 significantly prevented rDn-ACP protein from inhibiting lysozyme activity in vitro. Therefore, a vaccine incorporating rDn-ACP in particular could contribute to protection by enabling normal innate immune lysozyme function to aid bacterial clearance.

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s41598-019-46506-z - Version of Record
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Accepted/In Press date: 24 June 2019
e-pub ahead of print date: 11 July 2019

Identifiers

Local EPrints ID: 432758
URI: https://eprints.soton.ac.uk/id/eprint/432758
ISSN: 2045-2322
PURE UUID: 594f465b-b15b-4a01-a5e1-d769594cfe67
ORCID for Christian M. Orr: ORCID iD orcid.org/0000-0002-6137-8969
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139

Catalogue record

Date deposited: 26 Jul 2019 16:30
Last modified: 29 Aug 2019 00:38

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