Mark S. Smeltzer

Professor, Department of Microbiology & Immunology and Department of Orthopaedics

Bacteriology

Research Interest:  Molecular Pathogenesis of Staphylococcus aureus infections

Ph.D ., Kansas State University

Postdoctoral , Kansas State University

Phone: (501) 686-7958 or (501) 686-5254
Fax: (501) 686-5359

E-mail 

Laboratory Website

Research Description

Staphylococcus aureus is a commensal inhabitant of up to 50% of the healthy adult population, but it also has the capacity to cause serious and even life-threatening infections. These infections are difficult to treat for two reasons. The first is the emergence of antibiotic-resistant strains including methicillin-resistant S. aureus (MRSA) and, more recently, vancomycin-resistant S. aureus (VRSA). The second is that many S. aureus infections are associated with formation of a biofilm, which limits the efficacy of antimicrobial therapy even in those cases in which the infection is caused by a strain that does not exhibit high-level antibiotic resistance.  Important examples of particular interest to my lab are infections of musculoskeletal tissues including osteomyelitis and infections associated with implanted orthopaedic devices. With these issues in mind, the research focus in my laboratory is directed toward three primary areas. The first is directed toward understanding how S. aureus forms a biofilm and the nature of the adaptive response that allows S. aureus to persist within a biofilm. We believe this is important in that understanding these  issues may led to the development of therapeutic strategies that prevent biofilm formation or limit the ability of S. aureus to survive within a biofilm, and this could significantly enhance the efficacy of conventional antimicrobial therapy. The second research area is directed toward defining the regulatory circuits that control expression of S. aureus virulence factors.  These are complex circuits that collectively allow S. aureus to adapt to the host environment and ultimately cause disease, and we believe a better understanding of these circuits could also lead to the development of therapeutic strategies that enhance the efficacy of conventional antimicrobial agents but the host's ability to clear the infection. Importantly, there are important differences between regulatory circuits in the prototype laboratory strains that have been the primary research focus to date and the most prominent clinical isolates of S. aureus , and our specific emphasis is on understanding these differences and their impact on the ability to cause disease.  The third research focus is a collaborative effort with faculty in the Department of Orthopaedic Surgery and the Department of Radiology and Nuclear Medicine aimed at the detection, diagnosis and treatment of S. aureus musculoskeletal infection. Specifically, we are investigating the use of FDG-PET as a means of detecting infection in its early stages, the use of PCR-based methods that can be used to rapidly confirm the identity of the offending organism and address critical therapeutic issues including antibiotic resistance, and the development of alternative means of delivering effective concentrations of antibiotic directly to the site of infection. Taken together, we believe these three research areas represent a comprehensive approach that will ultimately lead to the development of new therapeutic agents and better methods of using these agents to treat staphylococcal musculoskeletal infection. At present, research in the Smeltzer laboratory is supported by grants from the National Institute of Allergy and Infectious Disease, the American Heart Association, and Cubist Pharmaceuticals.

References

Kanangat, S., Postlehwaite, A., Hasty, K., Kang, A., Smeltzer, M. , Appling, W. and Schaberg, D., Induction of multiple matrix metalloproteinases in human dermal and synovia fibroblasts by Staphylococcus aureus : Implications in the pathogenesis of septic arthritis and other soft tissue infections. Arthritis Research and Therapy , 2006 Nov 27;8(6):R176 [Epub ahead of print]

McLaren, A.C., McLaren, S.G, and Smeltzer, M.S. , 2006. Xylitol and glycine fillers increase permeability of PMMA to enhance elution of daptomycin. Clinical Orthopaedics and Related Research , 451:25-28.

Sambanthamoorthy, K., Smeltzer, M.S. and Elasri, M.O. 2006. Identification and characterization of msa (SA1233), a gene that is involved in expression of sarA and several virulence factors in Staphylococcus aureus . Microbiology , 152 :2559-2572.

Cassat, J.E., Dunman, P.M., Murphy, E.J., Projan, S.J., Beenken, K.E., Palm, K.J., Yang, S-J., Rice, K.C., Bayles, K.W. and Smeltzer, M.S. 2006. Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences by comparison to the laboratory strain RN6390. Microbiology , 152 :3075-3090.

Zharov, V.P., Mercer, K.E., Galitovskaya, E.N. and Smeltzer, M.S., 2006. Photothermal nanotherapeutics and nanodiagnostics for selective killing of bacteria targeted with gold nanoparticles. Biophysical Journal , 90 :619-627.

Jones-Jackson, L., Walker, R., Purnell, G., McLaren, S.G., Skinner, R.A., Thomas, J.R., Suva, L., Anaissie, E., Miceli, M., Nelson, C.L., Ferris, E. and Smeltzer, M.S. , 2005. Early detection of bone infection and differentiation from post-surgical inflammation using 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography (FDG-PET) in an animal model. Journal of Orthopaedic Research, 23 :1484-1489 .

Nelson, C.L., McLaren, A.C., McLaren, S.G., Johnson, J.W. and Smeltzer, M.S. , 2005. Is aseptic loosening really aseptic? Clinical Orthopaedics and Related Research , 437 :25-30.

Cassat J.E., Dunman, P.M., McAleese, F., Murphy, E., Projan, S.J. and Smeltzer, M.S. , Comparative genomics of Staphylococcus aureus musculoskeletal isolates. 2005. Journal of Bacteriology, 187 :547-592.

Koenig, R.L., Ray, J.L., Maleki, S.J., Smeltzer, M.S. and Hurlburt, B.K., Staphylococcus aureus AgrA binding to the RNAIII-agr regulatory region. 2004 . Journal of Bacteriology, 186 :7549-7555.

Beenken, K.E. Dunman, P.M., McAleese, F., Macapagal, D., Murphy, E., Projan, S.J., Blevins, J.S. Smeltzer, M.S. , 2004. Global gene expression in Staphylococcus aureus biofilms, Journal of Bacteriology , 186:4665-4684.

O'Leary, J.O., Langevin, M.J., Price, C.T.D., Blevins, J.S., Smeltzer, M.S. and Gustafson, J.E. 2004. Effects of sarA inactivation on the intrinsic multidrug resistance mechanism of Staphylococcus aureus . FEMS Microbiology Letters, 237:297-302.

Beenken, K.E., Blevins, J.S. and Smeltzer, M.S. 2003. Mutation of sarA impairs biofilm formation in Staphylococcus aureus. Infection and Immunity , 71:4206-4211.

Sterba, K.M., Mackintosh, S.G., Blevins, J.S., Hurlburt, B.K. and Smeltzer, M.S. 2003. Characterization of Staphylococcus aureus SarA binding sites. Journal of Bacteriology , 185:4410-4417.

Blevins, J.S. , Elasri, M.O., Skinner, R.A., Thomas, J.R. and Smeltzer, M.S. 2003. Role of sarA in the pathogenesis of Staphylococcus aureus musculoskeletal infection . Infection and Immunity, 71:516-523 .

Nugyen, L.L., Nelson, C.L., Saccente, M., Smeltzer, M.S. , Wassell, D.L. and McLaren, S.G. 2002. Detecting bacterial colonization of implanted orthopaedic devices by ultrasonication. Clinical Orthopaedics and Related Research , i403:29-37.

Nelson, C.L., McLaren, S.G., Skinner, R.A., Smeltzer , M.S. , Thomas, J.R. and Olsen, K.M., 2002. Treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets. Journal of Orthopaedic Research , 20:643-647.

Blevins, J.S., Beenkeen, K.E., Elasri, M.O., Hurlburt, B.K. and Smeltzer, M.S. 2002. Strain-dependent differences in the regulatory roles of sarA and agr in Staphylococcus aureus . Infection and Immunity, 70:470-480.

Elasri, M. O., Thomas, J.R., Skinner, R.A., Blevins, J.S., Beenken, K.E., Nelson, C.L. and Smeltzer, M.S. 2002. Staphylococcus aureus collagen adhesin contributes to the pathogenesis of osteomyelitis. Bone, 30:275-280 .

Mason, W.J., Blevins, J.S., Beenken, K.E., Wibowo, N., Ojha, N. and Smeltzer , M.S. 2001. Multiplex PCR protocol for the diagnosis of staphylococcal infection. Journal of Clinical Microbiology, 39:3332-3338

Smeltzer, M.S and Gillaspy, A.F. 2000. Molecular pathogenesis of staphylococcal osteomyelitis. Poultry Science , 79:1042-1049.

Snodgrass, J.L., Mohammed, N., Ross, J.M., Sau, S., Lee, C.Y. and Smeltzer, M.S. 1999. Functional characterization of the Staphylococcus aureus collagen adhesin B domain. Infection and Immunity , 67:3952-3959.

Ellington, J.K., Reilly, S.S., Warner, K.R., Ramp, W.K., Smeltzer, M.S. , Kellam, J.F. and Hudson , M.C. 1999. Mechanisms of Staphylococcus aureus invasion of cultured osteoblasts. Microbial Pathogenesis . 26 :317-323.

Blevins, J.S., Gillaspy, A.F., Rechtin, T.M., Hurlburt, B.K. and Smeltzer, M.S. 1999. The staphylococcal accessory regulator ( sar ) controls expression of the Staphylococcus aureus collagen adhesin gene ( cna ) in an agr -independent manner. Molecular Microbiology . 33 :317-326.

Rechtin, T.M., Gillaspy, A.F., Schumacher, M., Brennan, R.G., Smeltzer, M.S. and Hurlburt, B.K. 1999. Characterization of SarA virulence gene regulator of Staphylococcus aureus . Molecular Microbiology . 33 :307-316.

Marcos, J.Y., Soriano, A.C., Salazar, M.S., Moral, C.H., Ramos, S.S., Smeltzer, M.S. and Carrasco, G.N. 1999. Rapid identification and typing of Staphylococcus aureus by PCR-restriction fragment length polymorphism analysis of the aroA gene. Journal of Clinical Microbiology . 37 :570-574.

Gillaspy, A.F., Lee. C.Y., Sau, S., Cheung, A.L. and Smeltzer, M.S. 1998. Factors affecting the collagen binding capacity of Staphylococcus aureus. Infection and Immunity . 66 :3170-3178.

Smeltzer, M.S. , Gillaspy, A.F., Pratt, F.L., Jr. and Thames , M.D. 1997. Comparative evaluation of cna, fnbA, fnbB and hlb genomic fingerprinting for the epidemiological typing of Staphylococcus aureus . Journal of Clinical Microbiology . 35 :2444-2449.

Smeltzer, M.S. , Gillaspy, A.F., Pratt, F.L. and Iandolo, J.J. 1997. Prevalence and chromosomal map location of Staphylococcus aureus adhesin genes. Gene. 196 :249-259.

Gillaspy, A.F., Patti, J.M., Pratt, F.L., Jr., and Smeltzer, M.S. 1997. The Staphylococcus aureus collagen adhesin-encoding gene ( cna ) is within a discrete genetic element. Gene. 196 :239-248 .

Smeltzer, M.S. , Thomas, J.R., Hickmon, S.G., Skinner, R.A., Nelson, C.L., Griffith , D., Parr, T.R., Jr. and Evans, R.P. 1997. Characterization of a rabbit model of staphylococcal osteomyelitis. Journal of Orthopaedic Research, 15 :414-421.

Gillaspy, A.F., Patti, J.M., Pratt, F.L., Jr., and Smeltzer, M.S. 1997. Transcriptional regulation of the Staphylococcus aureus collagen adhesin gene ( cna ). Infection and Immunity, 65 :1536-1540.

Smeltzer, M.S. , Pratt, F.L., Jr., Gillaspy, A.F. and Young, L.A. 1996. Genomic fingerprinting for the epidemiological differentiation of Staphylococcus aureus clinical isolates. Journal of Clinical Microbiology , 34 :1364-1372.

Gillaspy, A.F., Hickmon, S.G., Skinner, R.A., Thomas, J.R., Nelson, C.L . and Smeltzer, M.S . 1995. Role of the accessory gene regulator ( agr ) in the pathogenesis of staphylococcal osteomyelitis. Infection and Immunity, 63 :3373-3380.

Smeltzer, M.S. , Hart, M.E. and Iandolo, J.J. 1994. The effect of lysogeny on the genomic organization of Staphylococcus aureus . Gene, 138 :51-57.

Chapes, S.K., Beharka, A.A., Hart, M.E., Smeltzer, M.S. and Iandolo, J.J. 1994. Differential RNA regulation by Staphylococcal enterotoxins A and B in murine macrophages. Journal of Leukocyte Biology , 55 :533-529 .

Smeltzer, M.S. , Hart, M.E. and Iandolo, J.J. 1993. Phenotypic characterization of xpr , a global regulator of extracellular virulence factors in Staphylococcus aureus . Infection and Immunity , 61 :919-925.

Hart, M.E., Smeltzer, M.S . and Iandolo, J.J. 1993. The extracellular protein regulator ( xpr ) affects exoprotein and agr mRNA levels in Staphylococcus aureus . Infection and Immunity , 175 :7895-7879.

Smeltzer, M.S ., Gill, S.R. and Iandolo, J.J. 1992. Localization of a chromosomal mutation affecting expression of extracellular lipase in Staphylococcus aureus . Journal of Bacteriology, 174 :4000-4006.

Smeltzer, M.S ., Hart, M.E. and Iandolo, J.J. 1992. Quantitative spectrophotometric assay for lipase activity in Staphylococcus aureus . Applied and Environmental Microbiology , 58 :2815-2819.

Rahaley, R.S., Dennis, S.M., and Smeltzer, M.S . 1983. Comparison of the enzyme-linked immunosorbent assay and complement fixation test for detecting Brucella ovis antibodies in sheep. Veterinary Record , 113 :467-470.

BOOK CHAPTERS:

Smeltzer, M.S. Characterization of staphylococcal adhesins for adherence to host tissues, Pgs. 411-444 In An, Y. H. and Friedman, R.J. (Eds), 2000, Handbook for Studying Bacterial Adhesion, Humana Press, Totowa , NJ .

Smeltzer, M.S. and Nelson, C.L. Osteomyelitis and septic arthritis. Pgs. 213-246 In Friedman, H., Bendinelli, M. and Honeyman, A. (Eds), 2001, Staphylococcus aureus Infection and Disease, Kluwer Academic/Plenum Publishing Corp., New York , NY .

Smeltzer, M.S. , Darville, T., Saccente, M. and Nelson, C.L. Staphylococcal osteomyelitis, In Staphylococcal Infectious Disease and Therapy, Proctor, R. (Ed), Marcel Dekker, Inc., New York, NY, in press.

Cassat, J.E., Lee, C.Y. and Smeltzer, M.S. Investigation of biofilm formation in clinical isolates of Staphylococcus aureus , In MRSA Protocols for Methods in Molecular Medicine, Yinduo Ji (Ed), Humana Press, Totowa, NJ, in press.