The Grunenwald Lab
Staphylococcus aureus stress responses at the host-pathogen interface
"Antimicrobial Resistance is a Slow Burning Fire"
Antimicrobial resistance (AMR) is considered a slow burning fire, with many mechanisms of resistance unknown, it is imperative that how these pathogens escape the host immune system as well as antibiotic treatment.
Antibiotic resistance can be believed to come from imporper use of antibiotics by patients with infections, however, resistance is a function of evolution. The proper usage of antibiotics does not keep the bacteria from becoming resitant, it prolongs the lifespan of the drug itself. Bacteria mutate all the time and eventually become to the treatments that they encounter. The mechansims of how these bacteria develop resistance is a crucial tipping factor in the race between host and pathogen.
Staphylococcus aureus is a Formidable Human Pathogen
S. aureus is a gram positive cocci, this bacteria asymptomatically colonizes 1/3 of individuals, and has the ability to infect nearly every body site. Infection can lead to conditions such as endocarditis, pneumonia, sepsis, toxic shock syndrome, osteomyelitis, and soft tissue infections. The public health threat of S. aureus is compounded by the rise of antibiotic resistance, most notably methicillin-resistant S. aureus (MRSA).
Central Hypothesis
The ability to readily sense environmental changes and accordingly shift cellular physiology opens niches for S. aureus within different tissues and confers intrinsic resistance to antibiotic treatments, contributing to S. aureus’s virulence, persistence, and success as a pathogen.
PASTA Kinase stk1
The eukaryotic like PASTA Kinase known as Stk1 has been shown to be a cirtical player in β-lactam resistance in S. aureus. Additionally, stk1 is highly conserved amongst Gram Positives, Myobacteria. This kinase can be considered a master regulator with controls over processes like carbon metabolism, biofilm, and most pertaining to our lab, cell wall stress.
Cell Wall Stress Response
There are many stress mechanisms in S.aureus that have evolved to make the bacteria more successful in its virulence. However, the mechanism of how S.aureus responds to antibiotic stress is still unknown. This is the main focus of the Grunenwald Lab.