Division of Microbiology (HFT-250)
National Center for Toxicological Research
U. S. Food and Drug Administration
Ph.D.: Microbiology, Mississippi State University, Starkville, Mississippi.
Post-Doctoral: Department of Pathology and Microbiology at Kansas State University, Manhattan, Kansas.
Phone: 870-543-7625/Office; 870-543-7952/Laboratory
Despite advancement of antimicrobial regimens and improved public health, Staphylococcus aureus, a gram-positive bacterium that resides on the skin and mucous membranes of approximately 30% of healthy individuals and as high as 90% of health care workers, remains an important bacterial pathogen responsible for numerous disease syndromes in humans and animals worldwide. The National Nosocomial Surveillance System ranks S. aureus as one of the most common causes of hospital-acquired infections as well. This organism is the leading cause of nosocomial pneumonia, surgical site infections, and nosocomial septicemia. In addition, methicillin-resistant S. aureus (MRSA) have continued to increase in frequency since the introduction of methicillin in the 1960s to the point now that MRSA have become endemic in many hospitals. Vancomycin has long been an important and reliable alternative to effectively treat MRSA since most MRSA are resistant to multiple antibiotics. However, the recent emergence of vancomycin-resistant S. aureus in hospital infections represents a major concern since vancomycin is our last line of defense against staphylococcal infections.
Because S. aureus is notorious for acquiring multiple antibiotic resistance determinants, it has become increasingly important that alternatives other than antibiotic therapy be developed for the prevention and treatment of diseases caused by Staphylococcus aureus. A promising therapeutic approach to treat staphylococcal infections is to target important steps in the pathogenesis of disease, thereby reducing the severity of infection and retarding disease progression. This would augment antimicrobial therapies and allow the patient’s own defenses to control and eliminate the infection. Passive immunization is an attractive approach to rapidly neutralize toxins, enzymes, and cell wall-associated proteins which are important in life-threatening disease.
In order to develop an alternative approach, like passive immunotherapy, for the prevention and treatment of staphylococcal disease, we believe a comprehensive analysis of all extracellular proteins produced by a number of representative S. aureus strains is required. Most extracellular proteins produced by S. aureus are virulence factor having been shown to be involved with some aspect of disease. While the genomes of several S. aureus strains have been completely sequenced and open reading frames assigned the importance of many of these open reading frames to the disease process remains to be determined. Because the global regulons, agr (accessory gene regulator) and sarA (staphylococcal accessory regulator), are key in the expression of extracellular proteins, primarily involved in the disease process, our recent efforts have focused on generating a comprehensive extracellular protein profile for several representative S. aureus strains and their agr and sarA mutants. Thus far, using one-dimensional SDS-PAGE and nano liquid chromatography coupled with mass spectrometry in tandem we have identified a total 1,341 unique proteins. This number represents approximately 50% of the genomic coding capacity of S. aureus. In addition, our proteomic work has developed an approach to semi-quantitate protein differences that exist with respect to time in growth and between strains. Because regulation of virulence genes by sarA and agr is not always an all or none process, we have utilized both peptide and protein scores generated from the LC/MS/MS data to semi-quantify the amount of certain proteins whose expression is known to be controlled by these regulators.
Other Research Interests
Staphylococcus aureus is a major cause of bacterial pneumonia in the elderly who recently recovered from infection with influenza. Because staphylococcal pneumonia is a life-threatening disease with a high mortality rate even with effective antimicrobial therapy it has become imperative that alternative forms of treatment be developed. Our primary interest is to determine the factors that promote staphylococcal pneumonia and develop a passive antibody therapy that will allow patients suffering from influenza to be protected from staphylococcal disease while they recover from flu.
Staphylococcus aureus is recognized as a major cause of hospital-acquired infections particularly in the area of surgical site infections. Once the skin is breached phagocytic immune cells are the major deterrent to staphylococcal invasion. Our goal is to understand the mechanisms that allow S. aureus to survive phagocytic attack by determining the role enzymes, such as catalase and superoxide dismutase, play in removing the toxic effects of oxygen radicals generated by the professional phagocytic cells of the body.
To our knowledge, the protective effect of Lactobacillus against S. aureus proliferation and subsequent exotoxin production in the vaginal environment has not been adequately addressed in the literature. Studies are just now underway to examine the protective role of naturally-occurring and bio-engineered strains of Lactobacillus against TSST-1 producing strains of S. aureus in both co-culture and simulated vaginal models.
Stingley, R.L., H. Liu, L.B. Mullis, C.A. Elkins, and M.E. Hart. 2014. Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1) production and Lactobacillus sp. growth in a defined medium simulating vaginal secretions. J. Microbiol. Methods 106:57-66.
Ibberson, C.B., C.L. Jones, S. Singh, M.C. Wise, M.E. Hart, D.V. Zurawski, and A.R. Horswill. 2014. Staphylococcus aureus hyaluronidase is a CodY-regulated virulence factor. Infect. Immun. 82:4253-4264.
Hart, M.E., L.H. Tsang, J. Deck, S.T. Dailey, R.C. Jones, H. Liu, H. Hu, M.J. Hart, and M.S. Smeltzer. 2013. Hyaluronidase expression and biofilm involvement in Staphylococcus aureus UAMS-1 and its sarA, agr, and sarA agr regulatory mutants. Microbiology 159:782-791.
Liu, H., Y. Gao, L.-R. Yu, R.C. Jones, C.A. Elkins, and M.E. Hart. 2011. Inhibition of Staphylococcus aureus by lysostaphin-expressing Lactobacillus plantarum WCFS1 in a modified genital tract secretion medium. Appl. Environ. Microbiol. 77:8500-8508.
Dr. Hart’s publications at PubMed.