Dr. Mark Smeltzer completed post-doctoral training in the laboratory of Dr. John J. Iandolo. It was in Dr. Iandolo’s lab that he was first introduced to Staphylococcus aureus as a bacterial pathogen. His goal during that time wasn’t so much to learn about S. aureus but rather to learn the experimental tools of molecular biology, which he then hoped to apply to an as yet to be determined biomedical problem.

Dr. Mark Smeltzer was recruited to UAMS in 1993 by the former chair of the Department of Orthopaedic Surgery, Dr. Carl L. Nelson. His recruitment to UAMS was based on the observation that S. aureus was and continues to be the leading cause of infections involving bone and indwelling orthopedic devices. These infections are remarkably difficult to treat even when the offending bacterial strain is susceptible to the preferred antibiotics.

This most often necessitates surgical intervention to remove infected tissues and/or indwelling devices, and even then the recurrence rate of infection is unacceptably high. Thus, a primary goal of the Smeltzer laboratory has been to understand the pathophysiology of Staphylococcus aureus as an orthopedic pathogen to a degree that can be exploited to prophylactic and therapeutic advantage.

This work has led to a focus on the staphylococcal accessory regulator (sarA), mutation of which limits the ability of S. aureus to form a biofilm to a degree that can be correlated with increased antibiotic susceptibility. It also limits overall virulence in the context of sepsis, osteomyelitis, and implant-associated infection. Based on this, current research funded by the Peer-Reviewed Orthopaedic

Research Program within the Congressionally-Directed Medical Research Program is aimed at identifying small molecule inhibitors of sarA and developing more effective methods for the delivery of these inhibitors, together with conventional antibiotics, directly to the site of infection.

In work funded by the National Institute of Allergy and Infectious Disease (NIAID), the Smeltzer lab is also investigating the mechanistic basis by which sarA impacts all of these clinically-relevant phenotypes. This has led to the hypothesis that the inability of sarA mutants to repress the production of extracellular proteases plays a critical role owing to the fact that it limits the accumulation of S. aureus virulence factors that contribute to these infections. The impact of these proteases is currently being exploited to comprehensively identify these virulence factors using a proteomics approach.

He is also working as Principal Investigator of Center for Microbial Pathogenesis and Host Inflammatory Responses, Arkansas

Mark Smeltzer, Ph.D. | UAMS Department of Microbiology and Immunology