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Assistant Professor of Microbiology
Office: 3-630 BSBIowa City, IA 52242
Office Phone: 319-384-4565
Lab: 3-615C BSBIowa City, IA 52242
BS, Microbiology, Iowa State UniversityMS, Microbiology, University of Illinois Urbana-ChampaignPhD, Microbiology, University of Illinois Urbana-Champaign
Post Doctoral, Harvard University
Biosciences Graduate ProgramDepartment of Microbiology Graduate ProgramInterdisciplinary Graduate Program in GeneticsMedical Scientist Training Program
Cells often respond to changes in their environment by altering gene expression. To accomplish this they are required to detect changes in their environment and then transduce that signal from outside the cell to a transcriptional response inside the cell. My laboratory focuses on understanding the basic molecular mechanisms involved in how cells sense and respond to extracellular signals. Our work focuses on how two Gram positive bacteria, the model organism Bacillus subtilis and the human pathogen Clostridium difficile, sense and respond to cell envelope stress.
B. subtilis ECF sigma factor activation: In B. subtilis we study the role of PrsW in activation of the Extra cytoplasmic function (ECF) sigma factor σW. Activation of σW occurs via proteolytic destruction of an anti-sigma factor RsiW. This degradation occurs via a process termed regulated intramembrane proteolysis (RIP) which is a highly conserved regulatory system present in both Gram positive and negative bacteria as well as Eukaryotes. A RIP pathway utilizes two proteases; a site-1 protease which initiates the activation of the system and a highly conserved site-2 protease which cleaves its substrate within the membrane only after cleavage by the site-1 protease. PrsW protein appears to be a novel site-1 protease that responds to antimicrobial peptides by initiating cleavage of the anti-σW factor, RsiW and leading to activation of σW. We are interested in understanding how PrsW detects antimicrobial peptides and further how PrsW initiates destruction of the anti-sigma factor.
C. difficile ECF sigma factors: C. difficile encodes three ECF sigma factors. We are studying the role of these ECF sigma factors in virulence and in response to cell envelope stress. We have found that expression of two of these sigma factors are dependent upon a homolog of the B. subtilis site-1 protease PrsW. We are focused on identifying the extracellular stresses these ECF sigma factors respond to and how they provide resistance to these stresses. In addition we are interested in understanding the role of these ECF sigma factors play in survival of the bacterium during an infection.
Cannibalism in B. subtilis: A second area of focus for the laboratory is the process of cannibalism which occurs during B. subtilis sporulation. We are interested in understanding both the mechanisms of toxin production and how the senses and responds to the toxin SDPC. Sporulation is initiated by the activation of a response regulator, Spo0A. The activity of Spo0A is not uniform across all cells of the population, in fact two subpopulations of B. subtilis exist, Spo0A-ON cells and Spo0A-OFF cells. The Spo0A-ON cells produce a toxin, SdpC, which is secreted and kills the SpoOA-OFF siblings. Normally, the Spo0A-ON cells resist the toxic effects of SdpC by producing a membrane protein, SdpI, which provides immunity to the toxin. The immunity protein is only produced when extracellular toxin is present. Interestingly, SdpI is also required to induce its own expression in response to extracellular toxin sequestering a transcriptional repressor, SdpR, to the membrane. The sequestration of SdpR by the SdpC/SdpI complex inhibits the activity of the repressor thereby allowing increased transcription of sdpI, and immunity to the toxin.
Pérez Morales T,
Production of the cannibalism toxin SDP is a multistep process that requires SdpA and SdpB.
2013 July. 195(14):3244-51.
The activity of σV, an extracytoplasmic function σ factor of Bacillus subtilis, is controlled by regulated proteolysis of the anti-σ factor RsiV.
2013 July. 195(14):3135-44.
Extra cytoplasmic function σ factor activation.
Curr Opin Microbiol.
2012 April. 15(2):182-8.
The Bacillus subtilis extracytoplasmic function σ factor σ(V) is induced by lysozyme and provides resistance to lysozyme.
2011 November. 193(22):6215-22.
PrsW is required for colonization, resistance to antimicrobial peptides, and expression of extracytoplasmic function σ factors in Clostridium difficile.
2011 August. 79(8):3229-38.
Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of Bacillus subtilis.
Proc Natl Acad Sci U S A.
2010 September 14. 107(37):16286-90.
Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis.
2006 July 15. 20(14):1911-22.
A three-protein signaling pathway governing immunity to a bacterial cannibalism toxin.
2006 February 10. 124(3):549-59.
Resolvase-in vivo expression technology analysis of the Salmonella enterica serovar Typhimurium PhoP and PmrA regulons in BALB/c mice.
2005 November. 187(21):7407-16.
HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium.
2005 August. 57(3):691-705.
Date Last Modified: 01/09/2014 -
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