Mark Smeltzer, Ph.D., is a Professor in the Department of Microbiology & Immunology, Department of Pathology, and Department of Orthopaedic Surgery at the University of Arkansas for Medical Sciences (UAMS). After receiving his Ph.D. from Kansas State University, Dr. 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. 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 orthopaedic 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. a primary goal of the Smeltzer laboratory has been to understand the pathophysiology of Staphylococcus aureus as an orthopaedic pathogen to a degree than can be exploited to prophylactic and therapeutic advantage.

Research Focus:
The primary goal of the Smeltzer laboratory has been to understand the pathophysiology of Staphylococcus aureus as an orthopaedic pathogen to a degree than 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. This impact of these proteases is currently being exploited to comprehensively identify these virulence factors using a proteomics approach.

Current Projects:
In collaboration with the laboratory of Dr. Jingyi Chen at the University of Arkansas-Fayetteville, the Smeltzer laboratory is exploring the use of a novel nanotherapeutic approach to the treatment of S. aureus infections. This approach employs photoactivatable antibody-conjugated, antibiotic-loaded gold nanocages to achieve a lethal photothermal effect and the simultaneous release of antibiotics directly at the surface of the targeted bacterial cells. Work to date confirms that it is capable of eradicating an established S. aureus biofilm, a result that cannot be achieved using any concentration of conventional antibiotic alone.

With support from the Texas Hip and Knee Foundation, and in collaboration with Dr. Alexandru Biris at the University of Arkansas at Little Rock and Dr. David Anderson at the University of Tennessee-Knoxville, the Smeltzer laboratory is also exploring the use of a nanoparticle based “scaffold” that can be used to deliver antibiotics directly to the site of infection and simultaneously promote bone regeneration across segmental bone defects following traumatic injury and/or radical surgical debridement.

Funding:
R01AI119380 – National Institute of Allergy and Infectious Disease (NIAID)
Defining the role of post-translation regulation by extracellular proteases in the pathogenesis of Staphylococcus aureus osteomyelitis.
September 1, 2021-August 31-2026.

P30-GM145393 – National Institute of General Medical Sciences (NIGMS)
Microbial pathogenesis and host inflammatory responses.
Role on project: Principal Investigator
The goal of this grant is to establish a self-sustaining Center of Biomedical Research Excellence in infectious disease around the central theme of understanding the impact of the host inflammatory response on the clinical outcome in infections caused by diverse microbial pathogens.
May 1, 2022-April 30, 2027

Texas Hip and Knee Center – Investigating a nanotherapeutic approach to the prevention and treatment of orthopaedic infections.
Role on project: Principal Investigator T
Research gift from an anonymous donor on overcoming the clinical problem of orthopaedic infections.