Microbiology

Alexander R. Horswill, PhD

Portrait

Associate Professor of Microbiology

Contact Information

Office: 540F EMRB
Iowa City, IA 52242
Office Phone: 319-335-7783

Lab: 540 EMRB
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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Thoendel M, Horswill A.  Random mutagenesis and topology analysis of the autoinducing peptide biosynthesis proteins in Staphylococcus aureus.  Mol Microbiol.  2013 January. 87(2):318-37.
[Link]

Zielinska A, Beenken K, Mrak L, Spencer H, Post G, Skinner R, Tackett A, Horswill A, Smeltzer M.  sarA-mediated repression of protease production plays a key role in the pathogenesis of Staphylococcus aureus USA300 isolates.  Mol Microbiol.  2012 December. 86(5):1183-96.
[Link]

Cech N, Junio H, Ackermann L, Kavanaugh J, Horswill A.  Quorum quenching and antimicrobial activity of goldenseal (Hydrastis canadensis) against methicillin-resistant Staphylococcus aureus (MRSA).  Planta Med.  2012 September. 78(14):1556-61.
[Link]

Laarman A, Mijnheer G, Mootz J, van Rooijen W, Ruyken M, Malone C, Heezius E, Ward R, Milligan G, van Strijp J, de Haas C, Horswill A, van Kessel K, Rooijakkers S.  Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis.  EMBO J.  2012 August 29. 31(17):3607-19.
[Link]

Kaplan J, Izano E, Gopal P, Karwacki M, Kim S, Bose J, Bayles K, Horswill A.  Low levels of β-lactam antibiotics induce extracellular DNA release and biofilm formation in Staphylococcus aureus.  MBio.  2012 July 31. 3(4):e00198-12.
[Link]

Pezzulo A, Tang X, Hoegger M, Alaiwa M, Ramachandran S, Moninger T, Karp P, Wohlford-Lenane C, Haagsman H, van Eijk M, Bánfi B, Horswill A, Stoltz D, McCray P, Welsh M, Zabner J.  Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung.  Nature.  2012 July 4. 487(7405):109-13.
[Link]

Gonzalez D, Okumura C, Hollands A, Kersten R, Akong-Moore K, Pence M, Malone C, Derieux J, Moore B, Horswill A, Dixon J, Dorrestein P, Nizet V.  Novel phenol-soluble modulin derivatives in community-associated methicillin-resistant Staphylococcus aureus identified through imaging mass spectrometry.  J Biol Chem.  2012 April 20. 287(17):13889-98.
[Link]

Hernandez F, Stockdale K, Huang L, Horswill A, Behlke M, McNamara J.  Degradation of nuclease-stabilized RNA oligonucleotides in Mycoplasma-contaminated cell culture media.  Nucleic Acid Ther.  2012 February. 22(1):58-68.
[Link]

Walker J, Horswill A.  A coverslip-based technique for evaluating Staphylococcus aureus biofilm formation on human plasma.  Front Cell Infect Microbiol.  2012. 2:39.
[Link]

Nygaard T, Pallister K, DuMont A, DeWald M, Watkins R, Pallister E, Malone C, Griffith S, Horswill A, Torres V, Voyich J.  Alpha-toxin induces programmed cell death of human T cells, B cells, and monocytes during USA300 infection.  PLoS One.  2012. 7(5):e36532.
[Link]

Date Last Modified: 07/31/2013 - 10:51:40