Georgiana E. Purdy, Ph.D.
- Professor of Molecular Microbiology and Immunology, School of Medicine
- Molecular Microbiology and Immunology Graduate Program, School of Medicine
- Program in Molecular and Cellular Biosciences, School of Medicine
Biography
Georgiana Purdy earned her bachelor’s degrees in Microbiology and Cell Science (BS, with honors) and History (BA, with honors) from the University of Florida in 1998. She subsequently obtained her Ph.D. from the University of Texas at Austin in 2003, working with Dr. Shelley Payne on the bacterial pathogen Shigella flexneri. Specifically, her thesis project focused on the role of S. flexneri periplasmic chaperones in virulence and the extracytoplasmic stress response. She then performed her postdoctoral training with Dr. David Russell at Cornell University, where she studied the host-pathogen interface between Mycobacterium tuberculosis and the macrophage. Her postdoctoral research demonstrated that the mycobactericidal properties of macrophages include the delivery of bacteria to a hydrolytic lysosome enriched in bactericidal Ub-peptides (Alonso et al., 2007). This novel insight dramatically impacted the field’s understanding of how M. tuberculosis was killed by activated and autophagic macrophages.
Dr. Purdy joined the OHSU MMI Department in 2008 as an Assistant Professor and established her independent research program focused on M. tuberculosis. The goals of the Purdy Lab are to further define the intrinsic resistance of the pathogen to the host immune response and antibiotics, delineate pathways in mycobacterial cell wall biogenesis, and identify targets and new strategies for future drug therapy. The lab combines the approaches of bacterial genetics, biochemistry and cell biology to achieve these goals.
Current efforts in the Purdy lab are focused on characterizing the function and regulation of mycobacterial MmpL cell wall lipid transporters that are crucial contributors to mycobacterial physiology and pathogenesis. Our focus is on MmpL11, which is conserved in non-pathogenic and pathogenic mycobacteria. MmpL11 plays a conserved role in mycobacterial biofilm formation. We have identified the lipids transported by MmpL11 as monomeromycolyl diacylglycerol (MMDAG), long chain TAGs, and mycolate wax ester (MWE). These lipids have been classified as “storage lipids” and are implicated in non-replicating persistence or latency. Consistent with this role, we showed that the M. tuberculosis mmpL11 mutant is impaired for survival and/or resuscitation compared to wild-type M. tuberculosis when incubated under nutrient and oxygen starvation. Furthermore, we showed that the mmpL11 mutant is less fit than wild-type in an in vitro granuloma model. Combined these data suggest that MmpL11 and its substrates are important for M. tuberculosis non-replicating persistence and latency.
Dr. Purdy became an Associate Professor in 2014 and received tenure in 2016. Work in the Purdy lab is funded by the NIH.
Education and training
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Degrees
- B.S., 1998, University of Florida
- B.A., 1998, University of Florida
- Ph.D., 2003, University of Texas Austin
Additional information
Publications
Publications
Cryo-EM structure of the Mycobacterium smegmatis MmpL5-AcpM complex
mBioStructural modeling and characterization of the Mycobacterium tuberculosis MmpL3 C-terminal domain
FEBS LettersStructures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition
PLoS BiologyM. tuberculosis AlkX Encoded by rv3249c Regulates a Conserved Alkane Hydroxylase System That Is Important for Replication in Macrophages and Biofilm Formation
Microbiology SpectrumComplete Characterization of Polyacyltrehaloses from Mycobacterium tuberculosis H37Rv Biofilm Cultures by Multiple-Stage Linear Ion-Trap Mass Spectrometry Reveals a New Tetraacyltrehalose Family
BiochemistryIdentification of residues important for M. tuberculosis MmpL11 function reveals that function is modulated by phosphorylation in the C-terminal domain
Molecular MicrobiologyMmpL3 is a lipid transporter that binds trehalose monomycolate and phosphatidylethanolamine
Proceedings of the National Academy of Sciences of the United States of AmericaMmpl proteins in physiology and pathogenesis of m. Tuberculosis
MicroorganismsMultiple-stage precursor ion separation and high resolution mass spectrometry toward structural characterization of 2,3-diacyltrehalose family from mycobacterium tuberculosis
SeparationsStructural and functional evidence that lipoprotein LpqN supports cell envelope biogenesis in Mycobacterium tuberculosis
Journal of Biological ChemistryKilling Mycobacterium tuberculosis in vitro
Microbiology SpectrumThe Mycobacterium tuberculosis MmpL11 cell wall lipid transporter is important for biofilm formation, intracellular growth, and nonreplicating persistence
Infection and ImmunityDiphenylether-Modified 1,2-Diamines with Improved Drug Properties for Development against Mycobacterium tuberculosis
ACS Infectious DiseasesConfinement-induced drug-tolerance in mycobacteria mediated by an efflux mechanism
PloS oneCrystal structure of the Mycobacterium tuberculosis transcriptional regulator Rv0302
Protein ScienceStructural basis for the regulation of the MmpL transporters of Mycobacterium tuberculosis
Journal of Biological ChemistryCrystal structure of the transcriptional regulator Rv0678 of Mycobacterium tuberculosis
Journal of Biological ChemistryCrystal structure of the transcriptional regulator Rv1219c of Mycobacterium tuberculosis
Protein ScienceNtrBC and Nac contribute to efficient shigella flexneri intracellular replication
Journal of bacteriologyAutophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques
PloS oneCharacterization of mycobacterial triacylglycerols and monomeromycolyl diacylglycerols from Mycobacterium smegmatis biofilm by electrospray ionization multiple-stage and high-resolution mass spectrometry
Analytical and Bioanalytical ChemistryMmpL11 protein transports mycolic acid-containing lipids to the mycobacterial cell wall and contributes to biofilm formation in Mycobacterium smegmatis
Journal of Biological ChemistryStructural and functional characterization of mycobactericidal ubiquitin-derived peptides in model and bacterial membranes
BiochemistryStructural determination of glycopeptidolipids of Mycobacterium smegmatis by high-resolution multiple-stage linear ion-trap mass spectrometry with electrospray ionization
Journal of Mass SpectrometryMycobacterium smegmatis RoxY is a repressor of oxyS and contributes to resistance to oxidative stress and bactericidal ubiquitin-derived peptides
Journal of bacteriologyTaking out TB - lysosomal trafficking and mycobactericidal ubiquitin-derived peptides
Frontiers in Microbiology