Department of Surgery - The Rumbaugh Lab
Kendra Rumbaugh, Ph.D.
Texas Tech Women in Science:
P. aeruginosa Pathogenesis and Biofilm Formation in Wounds
Infection with the Gram-negative pathogen Pseudomonas aeruginosa is one of the major causes of morbidity and mortality in severely burned patients, and the cause of debilitating chronic infections in diabetic patients. P. aeruginosa relies on an arsenal of cell-associated and secreted virulence factors to colonize and infect its host, and it persists and invades the immune system by building biofilms. We have recently shown that P. aeruginosa forms biofilm in burn wounds, specifically surrounding blood vessels and adipocytes. Currently, we are focusing on characterizing the biofilms formed in chronic diabetic wounds.
Interkingdom signaling between P. aeruginosa Quorum Sensing Molecules and Host Cells
Quorum sensing (QS) is a cell density-dependent signaling process used by many bacteria to coordinate gene expression in a population. QS in Gram-negative bacteria is controlled by diffusible molecules called autoinducers (AI) that function as ligands for regulatable transcription factors. At least two separate QS systems exist in P. aeruginosa, the LasI/LasR and RhlI/RhlR systems. The ligands for LasR and RhlR are N-3-oxododecanoyl- and N-butyryl- homoserine lactones, or PAI-1 and PAI-2, respectively. Several studies indicate that bacterial autoinducers, and PAI-1 in particular, can also influence gene expression in host eukaryotic cells, a process we’ve termed interkingdom signaling. We hypothesize that this regulatory process involves autoinducer receptor molecules in the host cells, possibly transcription factors. We have shown that P. aeruginosa autoinducers can efficiently enter mammalian cells and modulate gene expression potentially through the interaction of nuclear hormone receptors. In addition we have also recently shown that the nematode C. elegans can sense bacterial autoinducers and use this sensory information to ‘learn’ to avoid pathogens.
Quorum Sensing: Methods and Protocols
Since its early days in the 1990s, the Quorum Sensing (QS) field has grown from a few dozen laboratories, investigating the pathways, proteins, and chemicals that facilitate signaling in bacteria, to hundreds of groups that have integrated evolutionary biology, computer science, mathematics, engineering, and metagenomics to create an ever-expanding and dynamic field. In Quorum Sensing: Methods and Protocols, expert researchers provide an in-depth set of diverse protocols that span this broad area of study. Broken into three detailed sections, the volume covers the detection, isolation, and characterization of the QS signals made by both Gram- and Gram+ bacteria, determination of the function of QS signals in vivo, and the development of QS disruption strategies. Written in the highly successful Methods in Molecular Biology™ series format, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and expert tips on troubleshooting and avoiding known experimental pitfalls. Comprehensive and cutting-edge, Quorum Sensing: Methods and Protocols serves as an invaluable collection of easily accessible techniques for scientists seeking to further our knowledge about bacterial communication and its relation to humanity.
Antibiofilm Agents: From Diagnosis to Treatment and Prevention
This book provides a survey of recent advances in the development of antibiofilm agents for clinical and environmental applications. The fact that microbes exist in structured communities called biofilms has slowly become accepted within the medical community. We now know that over 80% of all infectious diseases are biofilm-related; however, significant challenges still lie in our ability to diagnose and treat these extremely recalcitrant infections.
Written by experts from around the globe, this book offers a valuable resource for medical professionals seeking to treat biofilm-related disease, academic and industry researchers interested in drug discovery, and instructors who teach courses on microbial pathogenesis and medical microbiology.
Stacy A, Everett J, Jorth P, Trivedi U, Rumbaugh KP, Whiteley M. Bacterial fight-and-flight responses enhance virulence in a polymicrobial infection. Proc Natl Acad Sci U S A. 2014 May 13. pii: 201400586. [Epub ahead of print]. PMID: 24825893
Gawande PV, Clinton AP, LoVetri K, Yakandawala N, Rumbaugh KP, Madhyastha S. Antibiofilm Efficacy of DispersinB® Wound Spray Used in Combination with a Silver Wound Dressing. Microbiology Insights 2014:7, 9-13. PMID: 24826078
Watters C, Everett JA, Haley C, Clinton A, Rumbaugh KP. Insulin Treatment Modulates the Host Immune System To Enhance Pseudomonas aeruginosa Wound Biofilms. Infect Immun. 2014 Jan;82(1):92-100.
Jorth P, Trivedi U, Rumbaugh K, Whiteley M. Probing bacterial metabolism during infection using high-resolution transcriptomics. J Bacteriol. 2013 Aug 23. [Epub ahead of print]. PMID:23974023
Ilangovan A, Fletcher M, Rampioni G, Pustelny C, Rumbaugh K, Heeb S, Cámara M, Truman A, Chhabra SR, Emsley J, Williams P. Structural Basis for Native Agonist and Synthetic Inhibitor Recognition by the Pseudomonas aeruginosa Quorum Sensing Regulator PqsR (MvfR). PLoS Pathog. 2013 Jul;9(7):e1003508. PMID:23935486
Filiatrault MJ, Tombline G, Wagner VE, Van Alst N, Rumbaugh K, Sokol P, Schwingel J, Iglewski BH. 2013. Pseudomonas aeruginosa PA1006, Which Plays a Role in Molybdenum Homeostasis, Is Required for Nitrate Utilization, Biofilm Formation, and Virulence. PLoS One.8(2):e55594. doi: 10.1371/journal.pone.0055594. Epub 2013 Feb 8. PMID:23409004
A. Korgaonkar , U. Trivedi , K.P. Rumbaugh, M. Whiteley. 2013. Community surveillance enhances P. aeruginosa virulence during polymicrobial infection. Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):1059-64. PMID:23277552
Watters C., Deleon K., Trivedi U., Griswold J.A., Lyte M., Hampel K.J., Wargo M.J., Rumbaugh K.P. 2012. Pseudomonas aeruginosa biofilms perturb wound resolution and antibiotic tolerance in diabetic mice. Med Microbiol Immunol. Sep 25. [Epub ahead of print]
Luckett, J.C.A, Darch, O., Watters, C., AbuOun, M., Ward, J., Goto, H., Heeb, S., Pommier, S., Rumbaugh, K., Camara, M., and Hardie, K.R. 2012. A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity. PLoS Pathogens. Aug;8(8):e1002854. PMID: 22927813
Padmanabhan V, Khan ZS, Solomon DE, Armstrong A, Rumbaugh KP, Vanapalli SA, Blawzdziewicz J. 2012. Locomotion of C. elegans: A Piecewise-Harmonic Curvature Representation of Nematode Behavior. PLoS One. 2012;7(7):e40121. PMID:22792224
Rumbaugh KP, Trivedi U, Watters C, Burton-Chellew MN, Diggle SP, West SA. 2012. Kin selection, quorum sensing and virulence in pathogenic bacteria. Proc Biol Sci. Sep 7;279(1742):3584-8. PMID:22648154
Stevens AM, Schuster M, Rumbaugh KP. 2012. Working together for the common good: cell-cell communication in bacteria. J Bacteriol. May;194(9):2131-41. PMID:22389476
Rumbaugh, K.P., Kaufmann, G.F. 2012. Exploitation of host signaling pathways by microbial quorum sensing signals. Curr Opin Microbiol. Apr;15(2):162-8. PMID: 22204809
Dalton, T., Dowd, S. E., Wolcott, R.D., Sun, Y., Watters, C., Griswold, J.A. and Rumbaugh, K.P. 2011. An in vivo polymicrobial biofilm wound infection model to study interspecies interactions. PLoS One. 6(11):e27317. PMID:22076151
Ramsey, M.C., Rumbaugh, K.P. and Whiteley, M. 2011. Metabolic cross-feeding enhances virulence in a model polymicrobial infection. PLoS Pathogens Mar;7(3):e1002012. PMID:21483753
Rumbaugh K.P. Fatal attraction: bacterial bait lures worms to their death. Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16411-2. Epub 2010 Sep 7.
Bryan, A., Koenig, L., Youn, E., Olmos, A., Li, G., Williams, S. C. and Rumbaugh, K.P. Human transcriptome analysis reveals a potential role for active transport in the metabolism of Pseudomonas aeruginosa autoinducers. Microbes Infect. 2010 Jul 24. [Epub ahead of print]
Teplitski, M., Mathesius, U. and Rumbaugh, K.P. Quorum sensing signal perception by mammalian and plant cells. Chem Rev. Chem Rev. 2010 Jun 10. [Epub ahead of print]
Rampioni, G., Pustelny, C., Fletcher, M.P., Wright, V. J., Bruce, M., Rumbaugh, K.P., Heeb, S., Camara, M., and Williams, P. 2010. Transcriptomic analysis reveals a global alkyl-quinolone-independent regulatory role for PqsE in facilitating the environmental adaptation of Pseudomonas aeruginosa to plant and animal hosts. Environ Microbiol. April 7. [Epub ahead of print]
Rumbaugh, K.P. and Carty, N. L. In vivo models of biofilm infection. In: Biofilm Infections. 2010. Springer, New York, NY. In press.
Jahoor, A., Williams, S.C., and Rumbaugh, K.P. Microbial signaling compounds as endocrine effectors. In: Microbial Endocrinology, Interkingdom Signaling in Infectious Disease and Health. 2010. Springer, New York, NY.
Wolcott, R.D.,Rumbaugh, K.P., James, G., Schultz, G., Phillips, P., Yang, Q., Watters, C., Stewart, P. S. and Dowd, S. E. 2010. Biofilm maturity studies indicate sharp debridement opens a time-dependent therapeutic window. J Wound Care 19(8) 320-328.
Rumbaugh, K.P., Diggle, S. P., Watters, C. W., Ross-Gillespie, A., Griffin, A. S. and West, S.A. 2009. Quorum sensing and the social evolution of bacterial virulence. Current Biology. Feb 19.
DeLeon, K., Watters, C., Baldin, F., Hamood, A., Griswold, J., Sreedharan, S., and Rumbaugh, K.P.. 2009. Efficacy of gallium maltolate in treating Pseudomonas aeruginosa infection in a thermally-injured mouse model. Antimicrob Agents Chemother. Apr; 53(4):1331-1337.
Rumbaugh, K.P., 2009. Should we be afraid of the Green Monster? Crit Care Med. May;37(5):1826-7.
Jahoor A., Patel R., Bryan, A., Do C., Krier J., Watters C., Wahli W., Li, G., Williams S.C. ,Rumbaugh, K.P. 2008. Peroxisome Proliferator Activated Receptors Mediate Host Cell Pro-inflammatory Responses to P. aeruginosa Autoinducer. 2008. J Bacteriol. Jan 4.
Rumbaugh, K.P. 2007. Convergence of Hormones and Autoinducers at the Host/Pathogen Interface. Anal Bioanal Chem. 387(2): 425-435.
Schaber J.A., Triffo W.J., Suh S.J., Oliver J.W., Hastert M.C., Griswold J.A., Auer M., Hamood A.N., Rumbaugh, K.P. 2007. Pseudomonas aeruginosa forms Biofilms in Acute Infection Independently of Cell-to-Cell Signaling. Infect Immun. 75(8)p. 3715-21.
Shiner, E.K., Terentyev, D., Bryan, A., Sennoune, S., Martinez-Zaguilan, R., Li, G., Gyorke, S., Williams, S.C. and Rumbaugh, K.P. 2006. Pseudomonas aeruginosa Autoinducer Modulates Host Cell Responses through Calcium Signaling. Cellular Microbiol. 8(10):1601-10.
Beale, E., Li, G., Tan, M.W., Rumbaugh, K.P. 2006. Caenorhabditis elegans Senses Bacterial Autoinducers. Appl Environ Microbiol. 72(7):5135-7.
Shiner, E.K., Rumbaugh, K.P., and S. C. Williams. 2005. Interkingdom Signaling: deciphering the language of homoserine lactones. FEMS Microbiol Rev. 29(5):935-47.
Haynes, A., Ruda, F., Oliver, J., Hamood. A.N., Griswold, J.A., Park, P.W., Rumbaugh, K.P. 2005. Syndecan-1 Shedding Contributes to Pseudomonas aeruginosa Sepsis. Infect Immun. 73(12):7914-21.
Haynes, A., Rumbaugh, K.P., Park, W. P., Hamood, A. N., Griswold, J. A. 2005. Protamine sulfate reduces the susceptibility of thermally injured mice to Pseudomonas aeruginosa infection. J. Surg. Res. 123: 109-117.
Shiner, E.K., S. Reddy, C. Timmons, G. Li, S.C. Williams, and Rumbaugh, K.P. 2004. Construction of a bacterial autoinducer detection system in mammalian cells. Biol Proced Online. 6:268-276.
Williams, S.C. Patterson, E. K., Carty, N.L., Griswold, J. A., Hamood, A. N. and Rumbaugh, K.P. 2004. Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells. J. Bacteriol. 186(8): 2281-7.
Rumbaugh, K.P. 2004. The Language of Bacteria…and Just About Everything Else. The Scientist. 18(17):26-27.
Rumbaugh, K.P., A. N. Hamood and J. A. Griswold. 2004. Cytokine Induction by the P. aeruginosa quorum sensing system during thermal injury. J Surg Res. 116:137-144.
Rumbaugh, K.P., J. A. Colmer, J. A. Griswold, and A. N. Hamood 2001. The effects of infection of thermal injury by Pseudomonas aeruginosa PAO1 on the murine cytokine response. Cytokine. 16:160-168.
Rumbaugh, K.P., J. A. Griswold, and A. N. Hamood 2000. The role of quorum sensing in the in vivo virulence of Pseudomonas aeruginosa. Microbes Infect. 2:1-11.
Rumbaugh, K.P., J. A. Griswold, B. H. Iglewski, and A. N. Hamood. 1999. Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infection. Infect. Immun. 67:5854-5862.
Rumbaugh, K.P., J. Griswold, and A. Hamood. 1999. Contribution of the regulatory gene lasR to the pathogenesis of Pseudomonas aeruginosa infection of burned mice. J Burn Care Rehabil. 20:42-49.
Rumbaugh, K.P., J. A. Griswold, and A. N. Hamood. 1999. Pseudomonas aeruginosa strains obtained from patients with tracheal, urinary tract, and wound infection: variations in virulence factors and virulence gene. J. Hosp. Infect. 43:211-218.
Rumbaugh, K.P., A. N. Hamood, and J. A. Griswold. 1999. Analysis of Pseudomonas aeruginosa clinical isolates for possible variations within the virulence genes exotoxin A and exoenzyme S. J Surg Res. 82:95-105.