Glycosaminoglycans (GAGs) are highly acidic polymers encountered by bacteria during the process of invasion. We are interested in understanding how pathogenic bacteria sense and respond to them. To begin, we studied interactions between the model pathogen, Staphylococcus aureus, and the model GAG, heparin. Literature suggests heparin sequesters cations needed for S. aureus growth and survival, due to its highly sulfated nature. We hypothesized that growth inhibition is a defense mechanism instead. Comparing the bacterial response to heparin and other highly sulfated polymers, we find that growth inhibition cannot be explained by the degree of sulfation. No other GAG blocked growth, and dextran sulfate, which contains 2-fold more sulfates than heparin, also failed to affect growth. This conclusively demonstrates that the bacterium specifically recognizes and responds to heparin. We have also demonstrated that specific signaling cascades (kdpD, hssS and nreB histidine kinases) are involved in sensing this GAG. Finally, we have shown that, S. aureus ceases its own growth in the presence of heparin to enhance virulence activities like biofilm formation. Overall, our work demonstrates that the pathogen has evolved to sense heparin, and switches from growth to virulence phenotypes. Understanding this phenomenon may help unravel details of how S. aureus invades hosts.

What bugs the bug? Staphylococcus aureus specifically senses and responds to heparin

ACS Spring 2022

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