Study reveals how bacterial pathogen adapts to dietary stress

In order to trigger illness, the human pathogen Staphylococcus aureus should adapt to the altering host setting. Many of those diversifications are mediated by means of two-component sign transduction programs (TCSs) that coordinate gene expression in response to environmental stimuli. In a brand new research reported within the Journal of Bacteriology, researchers at Illinois present perception into the sign transduction mechanism utilized by the staphylococcal TCS ArlRS in response to host-imposed manganese and glucose hunger.

“Signal transduction systems, such as ArlRS, play critical roles in allowing pathogens to adapt to the ever-changing environment that pathogens encounter during infection and thus are critical contributors to disease,” mentioned Thomas Kehl-Fie (MMG), an affiliate professor of microbiology and chief of the research.

To restrict S. aureus pathogenicity, the host sequesters essential nutrients—a course of referred to as dietary immunity—resembling manganese, zinc, and iron throughout an infection. However, profitable pathogens can circumvent this host protection and trigger illness. The researchers zeroed in on one mechanism utilized by S. aureus to evade this host response that depends on the ArlRS two-component system, which includes the histidine kinase ArlS and response regulator protein ArlR.

“We are particularly interested in elucidating how ArlR is activated, as this response regulator is implicated in the ability of S. aureus to both survive nutrient limitation and coordinate a response that attacks the host immune system,” mentioned Kehl-Fie.

“One of the interests of the Kehl-Fie lab is trying to understand how S. aureus resists nutritional immunity,” mentioned Paola Párraga Solórzano, Ph.D. pupil within the Kehl-Fie lab and first creator of the paper. “Since ArlR was suggested to be activated by other histidine kinases, we wanted to understand if ArlS was necessary for the response of ArlR to manganese and glucose-limited conditions.”

Although histidine kinases have particular interactions with their cognate response regulators, crosstalk can happen the place histidine kinases can activate non-cognate response regulators. In different research, a non-cognate histidine kinase was proven to activate ArlR, bringing the function of ArlS in resisting dietary immunity into query.

To decide if ArlS is important for activation of ArlR, a mutant pressure missing the arlS gene was assessed for his or her means to develop and activate ArlR in manganese-starved circumstances. These circumstances had been achieved utilizing calprotectin, an immune effector that sequesters manganese away from pathogens like S. aureus. The research revealed that ArlS is important for activation of ArlR underneath these circumstances, mentioned Párraga Solórzano.

Because glucose is the popular carbon supply for S. aureus, Párraga Solórzano evaluated the function of ArlS in glucose-starved circumstances. While ArlR nonetheless had a stage of exercise within the absence of ArlS, ArlS was required for full activation in response to glucose limitation, mentioned Párraga Solórzano.

“We were able to understand how these signaling mechanisms work and how S. aureus coordinates responses to stressful conditions normally encountered during infection,” mentioned Párraga Solórzano. “We determined that ArlS is important for the response of S. aureus to both manganese starvation and glucose limitation.”

Preliminary research that furthered this work had been performed by co-author and former undergraduate pupil Angela Shupe.