Glycomic Analysis Reveals a Conserved Response to Bacterial Sepsis Induced by Different Bacterial Pathogens

Abstract

Sepsis is an extreme inflammatory response to infection that occurs in the bloodstream and causes damage throughout the body. Glycosylation is known to play a role in immunity and inflammation, but the role of glycans in sepsis is not well-defined. Herein, we profiled the serum glycomes of experimental mouse sepsis models to identify changes induced by 4 different clinical bacterial pathogens (Gram-positive: Streptococcus pneumoniae and Staphylococcus aureus , Gram-negative: Escherichia coli and Salmonella Typhimurium) using our lectin microarray technology. We observed global shifts in the blood sera glycome that were conserved across all four species, regardless of whether they were Gram positive or negative. Bisecting GlcNAc was decreased upon sepsis and a strong increase in core 1/3 O -glycans was observed. Lectin blot analysis revealed a high molecular weight protein induced in sepsis by all four bacteria as the major cause of the core 1/3 O -glycan shift. Analysis of this band by mass spectrometry identified interalpha-trypsin inhibitor heavy chains (ITIHs) and fibronectin, both of which are associated with human sepsis. Shifts in the glycosylation of these proteins were observed. Overall, our work points toward a common mechanism for bacterially induced sepsis, marked by conserved changes in the glycome.

The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice

“…Bacteremia is a bacterial infection occurring in the bloodstream. A bacteremia may develop into sepsis and septic shock, causing overwhelming inflammation, immune system dysfunction, multiple organ failure, and death 7 – 9 . Gram-positive bacteria Staphylococcus aureus ( S. aureus ) is one of the most common pathogens that cause various infections in hospitals and communities, posing a medical challenge 10 , 11 .…”

α2,6-Sialylation Is Upregulated in Severe COVID-19, Implicating the Complement Cascade

“… 14 An advantage of this method is that probes that identify significant changes in the glycome can then be used for further glycoproteomic and histochemical studies. High-throughput glycomic analysis using our established array technology has revealed new roles for glycans in cancer biology, 17 host–pathogen interactions, 18 , 19 and vaccine response. 20 In brief, each sample was fluorescently labeled ( S , Alexa Fluor 555 labeled) and mixed with an equal amount of an orthogonally labeled reference standard ( R , Alexa Fluor 647 labeled commercial plasma).…”

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

“…Further, the creation of lectin arrays [ 8 – 9 ], which employ a diverse set of characterized lectins, has enabled high-throughput glycan profiling, thereby advancing both diagnostic methods and biomarker discovery. Examples include arrays that can rapidly profile alterations in glycosylation patterns, pivotal in many diseases and inflammatory changes [ 10 – 11 ].…”