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

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.