Location

Microbiology & Immunology

TBRC C3960

General Interests

Microbial Pathogenesis, Bacterial Toxins, Genetic Regulation of Exotoxin Synthesis

Research Areas

Pseudomonas aeruginosa, which usually resides in soil and water environments, can infect compromised hosts to cause significant morbidity and mortality. The pathogenesis of this organism in humans involves multiple virulence factors whose expression patterns are integrated with growth and replication. Virulence is mediated mainly by the expression of cell surface molecules, sensing and signal transduction systems, motility, chemotaxis and the ability to secrete a number of destructive enzymes including proteases, lipases, neuraminidase, toxins and capsular material. My long-term objective is to understand the interplay between host and bacterial factors that lead to life-threatening infections with P. aeruginosa. We have focused on the relationship between expression of toxins injected by the type III system and Pseudomonas pathogenesis in acute infection models. The local as well as the systemic delivery of toxins emphasize the pathogenic potential of the bacterium. Our hypothesis is that delivery of the type III toxins inhibits the uptake and destruction of P. aeruginosa during the initial stages of colonization, allowing multiplication past the point of resolution by innate immune mechanisms in compromised hosts. The outcome of infection is then determined by the extent of injury or compromised state of the host, the expression patterns of the various toxins, proteases and other destructive enzymes, and the host response.

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Current Members

Molly Riegert

Research Technologist III

mriegert@mcw.edu

Samuel DeCero

Graduate Student

sdecero@mcw.edu

Conformational Changes and Membrane Interaction of the Bacterial Phospholipase, ExoU: Characterization by Site-Directed Spin Labeling.

(Feix JB, Kohn S, Tessmer MH, Anderson DM, Frank DW.) Cell Biochem Biophys. 2019 Mar;77(1):79-87 PMID: 30047043 PMCID: PMC6347562 SCOPUS ID: 2-s2.0-85050694302 07/27/2018
Identification and Verification of Ubiquitin-Activated Bacterial Phospholipases.

(Tessmer MH, Anderson DM, Pickrum AM, Riegert MO, Frank DW.) J Bacteriol. 2019 Feb 15;201(4) PMID: 30455285 PMCID: PMC6351748 SCOPUS ID: 2-s2.0-85060624878 11/21/2018
Identification of a ubiquitin-binding interface using Rosetta and DEER.

(Tessmer MH, Anderson DM, Pickrum AM, Riegert MO, Moretti R, Meiler J, Feix JB, Frank DW.) Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):525-530 PMID: 29295930 PMCID: PMC5776994 SCOPUS ID: 2-s2.0-85042128224 01/04/2018
Pseudomonas aeruginosa infection liberates transmissible, cytotoxic prion amyloids.

(Balczon R, Morrow KA, Zhou C, Edmonds B, Alexeyev M, Pittet JF, Wagener BM, Moser SA, Leavesley S, Zha X, Frank DW, Stevens T.) FASEB J. 2017 Jul;31(7):2785-2796 PMID: 28314768 PMCID: PMC5471513 SCOPUS ID: 2-s2.0-85021662814 03/21/2017
Structure and Dynamics of Type III Secretion Effector Protein ExoU As determined by SDSL-EPR Spectroscopy in Conjunction with De Novo Protein Folding.

(Fischer AW, Anderson DM, Tessmer MH, Frank DW, Feix JB, Meiler J.) ACS Omega. 2017 Jun 30;2(6):2977-2984 PMID: 28691114 PMCID: PMC5494639 07/12/2017
Cooperative Substrate-Cofactor Interactions and Membrane Localization of the Bacterial Phospholipase A2 (PLA2) Enzyme, ExoU.

(Tessmer MH, Anderson DM, Buchaklian A, Frank DW, Feix JB.) J Biol Chem. 2017 Feb 24;292(8):3411-3419 PMID: 28069812 PMCID: PMC5336173 SCOPUS ID: 2-s2.0-85013836015 01/11/2017
The Pseudomonas aeruginosa Exoenzyme Y: A Promiscuous Nucleotidyl Cyclase Edema Factor and Virulence Determinant.

(Morrow KA, Frank DW, Balczon R, Stevens T.) Handb Exp Pharmacol. 2017;238:67-85 PMID: 28181005 PMCID: PMC6103630 SCOPUS ID: 2-s2.0-85018986099 02/10/2017
Pseudomonas aeruginosa exoenzymes U and Y induce a transmissible endothelial proteinopathy.

(Morrow KA, Ochoa CD, Balczon R, Zhou C, Cauthen L, Alexeyev M, Schmalzer KM, Frank DW, Stevens T.) Am J Physiol Lung Cell Mol Physiol. 2016 Feb 15;310(4):L337-53 PMID: 26637633 PMCID: PMC4754902 SCOPUS ID: 2-s2.0-84958559488 12/08/2015
Heterogeneity of pulmonary endothelial cyclic nucleotide response to Pseudomonas aeruginosa ExoY infection.

(Morrow KA, Seifert R, Kaever V, Britain AL, Sayner SL, Ochoa CD, Cioffi EA, Frank DW, Rich TC, Stevens T.) Am J Physiol Lung Cell Mol Physiol. 2015 Nov 15;309(10):L1199-207 PMID: 26386118 PMCID: PMC4652153 SCOPUS ID: 2-s2.0-84947231546 09/20/2015
Cross Kingdom Activators of Five Classes of Bacterial Effectors.

(Anderson DM, Feix JB, Frank DW.) PLoS Pathog. 2015 Jul;11(7):e1004944 PMID: 26203905 PMCID: PMC4512716 SCOPUS ID: 2-s2.0-84938811382 07/24/2015
cCMP and cUMP occur in vivo.

(Bähre H, Hartwig C, Munder A, Wolter S, Stelzer T, Schirmer B, Beckert U, Frank DW, Tümmler B, Kaever V, Seifert R.) Biochem Biophys Res Commun. 2015 May 15;460(4):909-14 PMID: 25838203 PMCID: PMC4765920 SCOPUS ID: 2-s2.0-84937760629 04/04/2015
Pseudomonas aeruginosa toxins

(Rolsma S, Frank DW, Barbieri JT.) The Comprehensive Sourcebook of Bacterial Protein Toxins. 5 June 2015:133-160 SCOPUS ID: 2-s2.0-85053197841 06/05/2015

Frank Laboratory