Monash University

education📍 Melbourne, Australia
Monash University
2
Alpha-gal Syndrome Publications
1
Alpha-gal Syndrome Researchers

Associated Institutions

Box Hill Hospital
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Burnet Institute
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Australian Regenerative Medicine Institute
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Monash Medical Centre
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Frankston Hospital
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Alpha-gal Syndrome Researchers

Publications

Immunoglobulin E Sensitization to Mammalian Oligosaccharide Galactose-α-1,3 (α-Gal) Is Associated With Noncalcified Plaque, Obstructive Coronary Artery Disease, and ST-Segment-Elevated Myocardial Infarction.

Vernon ST, Kott KA, Hansen T, Finemore M, Baumgart KW, et al.
Arteriosclerosis, thrombosis, and vascular biology •

Treating known risk factors for coronary artery disease (CAD) has substantially reduced CAD morbidity and mortality. However, a significant burden of CAD remains unexplained. Immunoglobulin E sensitization to mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal) was recently associated with CAD in a small observational study. We sought to confirm that α-Gal sensitization is associated with CAD burden, in particular noncalcified plaque. Additionally, we sort to assess whether that α-Gal sensitization is associated with ST-segment-elevated myocardial infarction (STEMI) Methods: We performed a cross-sectional analysis of participants enrolled in the BioHEART cohort study. We measured α-Gal specific-immunoglobulin E antibodies in serum of 1056 patients referred for CT coronary angiography for suspected CAD and 100 selected patients presenting with STEMI, enriched for patients without standard modifiable risk factors. CT coronary angiograms were assessed using coronary artery calcium scores and segmental plaque scores. α-Gal sensitization was associated with presence of noncalcified plaque (odds ratio, 1.62 [95% CI, 1.04-2.53], =0.03) and obstructive CAD (odds ratio, 2.05 [95% CI, 1.29-3.25], =0.002), independent of age, sex, and traditional risk factors. The α-Gal sensitization rate was 12.8-fold higher in patients with STEMI compared with matched healthy controls and 2.2-fold higher in the patients with STEMI compared with matched stable CAD patients (17% versus 1.3%, =0.01 and 20% versus 9%, =0.03, respectively). α-Gal sensitization is independently associated with noncalcified plaque burden and obstructive CAD and occurs at higher frequency in patients with STEMI than those with stable or no CAD. These findings may have implications for individuals exposed to ticks, as well as public health policy. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001322224.

Structure and biosynthetic locus of the lipopolysaccharide outer core produced by Pasteurella multocida serovars 8 and 13 and the identification of a novel phospho-glycero moiety.

Harper M, St Michael F, Vinogradov E, John M, Steen JA, et al.
Glycobiology •

Pasteurella multocida strains are classified into 16 Heddleston serovars on the basis of the lipopolysaccharide (LPS) antigens expressed on the surface of the bacteria. The LPS structure and the corresponding LPS outer core biosynthesis loci of strains belonging to serovars 1, 2, 3, 5, 9 and 14 have been characterized, revealing a clear structural basis for serovar classification. However, several of these serovars are genetically related, sharing the same LPS outer core biosynthesis locus, but producing different LPS molecules as a result of mutations within LPS assembly genes. In this article, we report that the P. multocida type strains belonging to serovars 8 and 13 share the same LPS outer core biosynthesis locus and produce structurally related LPS molecules. Structural analysis of the serovar 8 LPS revealed an inner core that is conserved among P. multocida strains and the following outer core structure: X-(1-6)-(1S)GalaNAC-(1-4-6)-α-Gal-(1-3)-β-Gal(PEtn)-(1-4)-L,D-α-Hep-(1-6) where X is a unique phospho-glycero moiety, 1-((4-aminobutyl)amino)-3-hydroxy-1-oxopropan-2-yl hydrogen phosphate, attached to the sixth position of (1S)GalaNAc. For serovar 13, the LPS structure is the same except for the absence of the terminal phospho-glycero moiety. Analysis of the common outer core biosynthesis locus from the serovar 8 and 13 type strains identified three genes that we predict are involved in the biosynthesis of this terminal moiety. Furthermore, bioinformatic comparisons with the characterized LPS outer core glycosyltransferases from Actinobacillus pleuropneumoniae serovar 1, strain 4074, allowed us to assign a function for each of the glycosyltransferases encoded within the serovar 8/13 LPS outer core biosynthesis locus.