Biosciences Graduate Program

Alexander R. Horswill, PhD

Portrait

Associate Professor of Microbiology

Contact Information

Office: 540F Eckstein Medical Research Building
431 Newton Rd
Iowa City, IA 52242
Office Phone: 319-335-7783

Lab: 540 Eckstein Medical Research Building
431 Newton Rd
Iowa City, IA 52242
Phone: 319-335-7996

Email: alex-horswill@uiowa.edu
Web: Horswill Lab Website

Education

BS, Bacteriology, University of Wisconsin - Madison
PhD, Bacteriology, University of Wisconsin - Madison

Post Doctoral, Chemistry, Pennsylvania State University

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Microbiology Graduate Program
Medical Scientist Training Program

Research Summary

Many critical processes in bacteria are regulated by cell density. By producing chemical signals, bacteria can communicate and coordinate regulatory events in large populations. These signals accumulate to a critical threshold and elicit a regulatory response at the appropriate cell density. This phenomenon of density-dependent regulation is frequently termed quorum sensing or autoinduction, and the signals controlling this process are acyl-homoserine lactones (HSLs) in Gram negative bacteria and peptides in Gram positive bacteria. While HSLs have been investigated extensively, studies on peptide regulation have lagged behind, even though many Gram positive bacteria regulate pathogenesis using these signals.

My research focuses on the peptide quorum sensing system of Staphylococcus aureus. The agr locus of this bacterium produces an extracellular peptide signal, called an autoinducing peptide (AIP). At the correct cell population, this signal controls expression of the virulence response, including down-regulating the expression of surface proteins, such as adhesins and antigens, and up-regulating the expression of virulence factors, such as hemolysins, proteases, and toxins. Structural studies have determined that the S. aureus AIP is an eight-residue peptide, with the five C-terminal residues cyclized into a thiolactone ring. However, there is little information available about the proteins involved in the maturation and export process, and the details of the biosynthetic mechanism remain unclear. My laboratory will take genetic, molecular, and biochemical approaches towards defining the route of AIP biosynthesis and the mode of action of these signals. With a better understanding of the AIP system, it will be possible to develop AIP inhibitors that could block S. aureus virulence. We will explore cutting-edge peptide technologies to discover such inhibitors and investigate their implementation in S. aureus.

Recent efforts have suggested that S. aureus quorum sensing and biofilm formation are interconnected. The ability of S. aureus to develop biofilms on medical implants is an important determinant in infections, high-lighting the need for more studies in this area. As we learn more about AIP biosynthesis and regulation, this research will be extended toward studies on biofilms, with a goal of improving our understanding of this connection.

Center, Program and Institute Affiliations

Center for Biocatalysis and Bioprocessing
Center for Immunology and Immune-based Diseases
Inflammation Program

Selected Publications

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Figueroa M, Jarmusch A, Raja H, El-Elimat T, Kavanaugh J, Horswill A, Cooks R, Cech N, Oberlies N.  Polyhydroxyanthraquinones as quorum sensing inhibitors from the guttates of Penicillium restrictum and their analysis by desorption electrospray ionization mass spectrometry.  J Nat Prod.  2014 June 27. 77(6):1351-8.
[Link]

Sully E, Malachowa N, Elmore B, Alexander S, Femling J, Gray B, DeLeo F, Otto M, Cheung A, Edwards B, Sklar L, Horswill A, Hall P, Gresham H.  Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance.  PLoS Pathog.  2014 June 12. 10(6):e1004174.
[Link]

Flack C, Zurek O, Meishery D, Pallister K, Malone C, Horswill A, Voyich J.  Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli.  Proc Natl Acad Sci USA.  2014 May 13. 111(19):E2037-45.
[Link]

Sommerfield Ross S, Tu M, Falsetta M, Ketterer M, Kiedrowski M, Horswill A, Apicella M, Reinhardt J, Fiegel J.  Quantification of confocal images of biofilms grown on irregular surfaces.  J Microbiol Methods.  2014 May. 100:111-20.
[Link]

Kiedrowski M, Crosby H, Hernandez F, Malone C, McNamara J, Horswill A.  Staphylococcus aureus Nuc2 Is a Functional, Surface-Attached Extracellular Nuclease.  PLoS One.  2014 April 21. 9(4):e95574.
[Link]

White M, Boyd J, Horswill A, Nauseef W.  Phosphatidylinositol-specific phospholipase C contributes to survival of Staphylococcus aureus USA300 in human blood and neutrophils.  Infect Immun.  2014 April. 82(4):1559-71.
[Link]

Hernandez F, Huang L, Olson M, Powers K, Hernandez L, Meyerholz D, Thedens D, Behlke M, Horswill A, McNamara J.  Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe.  Nat Med.  2014 March. 20(3):301-6.
[Link]

Cech N, Horswill A.  Small-molecule quorum quenchers to prevent Staphylococcus aureus infection.  Future Microbiol.  2013 December. 8:1511-4.
[Link]

Snowden J, Beaver M, Beenken K, Smeltzer M, Horswill A, Kielian T.  Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation.  PLoS One.  2013 December. 8(12):e84089.
[Link]

Walker J, Crosby H, Spaulding A, Salgado-Pabón W, Malone C, Rosenthal C, Schlievert P, Boyd J, Horswill A.  The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis.  PLoS Pathog.  2013 December. 9(12):e1003819.
[Link]

Date Last Modified: 06/07/2014 - 21:56:23