Dunman Laboratory Research Overview:
Staphylococcus aureus is a Gram-positive bacterial pathogen that is reported to cause more U.S. deaths annually than HIV. Acinetobacter baumannii is a Gram-negative pathogen that is emerging as a predominant cause of infections within military personnel injured during Operation Iraqi Freedom and has recently caused deadly outbreaks in the U.S., South America, and Europe. In addition to causing high incidences of morbidity and mortality, both organisms have also developed resistance to all currently available antibiotics, further amplifying public health concern and accentuating the need for new antibiotics for the treatment of S. aureus and A. baumannii infections.
Our laboratory uses S. aureus and A. baumannii as model organisms to study bacterial pathogenesis and develop novel strategies for the therapeutic intervention of bacterial infections. That work has revealed that most bacterial virulence factors are post-transcriptionally regulated in a manner that involves the modulation of their mRNA turnover. Current laboratory projects are geared toward characterizing the molecular components that govern 'native' and temporal changes in mRNA degradation. These factors can be broadly categorized as either: small non-coding RNAs, ribonucleases, or RNA binding proteins. We have purified and exploited several of these factors as targets for antimicrobial drug discovery.
Relevant Recent Publications:
1. Small molecule inhibitors of Staphylococcus aureus RnpA alter cellular mRNA turnover, exhibit antimicrobial activity, and attenuate pathogenesis. Olson PD, Kuechenmeister LJ, Anderson KL, Daily S, Beenken KE, Roux CM, Reniere ML, Lewis TL, Weiss WJ, Pulse M, Nguyen P, Simecka JW, Morrison JM, Sayood K, Asojo OA, Smeltzer MS, Skaar EP, and Dunman PM. PLoS Pathogens 2011 (in press).
2. Characterizing the effects of inorganic acid and alkaline shock on the Staphylococcus aureus transcriptome and messenger RNA turnover. Anderson KL, Roux CM, Olson MW, Luong TT, Lee CY, Olson R, and Dunman PM. FEMS Immunol Med Microbiol 2010 60(3):208.
3. Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence. Wyatt MA, Wang W, Roux CM, Beasley FC, Heinrichs DE, Dunman PM and Magarvey NA. Science 2010 329(5989):294.
4. Inactivation of phospholipase D diminishes Acinetobacter baumannii pathogenesis. Jacobs AC, Hood I, Boyd KL, Olson PD, Morrison JM, Carson S, Sayood K, Iwen PC, Skaar EP, and Dunman PM. Infect Immun 2010 78(5):1952.