Kathleen A. McDonough
    Plague bacilli exhibit a growth defect at host temperatures when the global regulatory gene hfq is deleted (middle panel).
    Plague bacilli exhibit a growth defect at host temperatures when the global regulatory gene hfq is deleted (middle panel), most likely due to dysregulation of one or more small regulatory RNA molecules. Addition of a good hfq gene copy restores normal growth (bottom). The top panel includes wild type Y. pestis for reference.

Kathleen A. McDonough, Ph.D.

Director, Division of Infectious Disease
Professor, School of Public Health, Biomedical Sciences
Bacterial Pathogenesis
Ph.D., Stanford University
Postdoctoral training: Howard Hughes Medical Institute, Albert Einstein College of Medicine

Research Interests

The focus of the McDonough Laboratory is gene regulation in the context of bacterial pathogenesis, or the means by which bacteria cause disease. The team is primarily interested in two well known pathogens: Mycobacterium tuberculosis, the bacterium that causes TB, and Yersinia pestis, the etiologic agent of bubonic and pneumonic plague. The lab uses a variety of techniques in their studies with both pathogens, ranging from molecular genetics and biochemistry to bioinformatics, proteomics and fluorescence microscopy.

The long term objective of the laboratory’s Mtb work is to gain a better understanding, at the molecular and cellular levels, of how this highly pathogenic bacterium establishes infection so that effective strategies can be developed to prevent tuberculosis infection and/or disease. A major current emphasis in the laboratory is on Mtb gene expression in host-associated conditions, and this work encompasses two major projects. The first project focuses on cyclic AMP (cAMP) signaling as a global gene regulatory mechanism, while the second involves the characterization of a family of macrophage-induced genes that are thought to play a role in the establishment of TB dormancy. A long term goal of the Yersinia program is to understand the specific roles of gene regulation in plague transmission and pathogenesis as Y. pestis cycles between its flea vectors and mammalian hosts. A second objective of the Yersinia work is to understand, at the cellular and molecular levels, what differentiates Y. pestis, the etiologic agent of plague, from the closely related enteric pathogen Y. pseudotuberculosis.

Select Publications
McDowell JR, Bai G, Lasek-Nesselquist E, Eisele LE, Wu Y, Hurteau G, Johnson R, Bai Y, Chen Y, Chan J, McDonough KA. Mycobacterial phosphodiesterase Rv0805 is a virulence determinant and its cyclic nucleotide hydrolytic activity is required for propionate detoxification. Mol Microbiol. 2023; 119 (4): 401-422. DOI: 10.1111/mmi.15030
Lee WT, Girardin RC, Dupuis AP, Kulas KE, Payne AF, Wong SJ, Arinsburg S, Nguyen FT, Mendu DR, Firpo-Betancourt A, Jhang J, Wajnberg A, Krammer F, Cordon-Cardo C, Amler S, Montecalvo M, Hutton B, Taylor J, McDonough KA. Neutralizing Antibody Responses in COVID-19 Convalescent Sera. J Infect Dis. 2021; 223 (1): 47-55. DOI: 10.1093/infdis/jiaa673
Girardin RC, Dupuis AP, Payne AF, Sullivan TJ, Strauss D, Parker MM, McDonough KA. Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for Coronavirus Disease 2019 Convalescent Plasma. J Infect Dis. 2021; 223 (5): 743-751. DOI: 10.1093/infdis/jiaa803
Väre VYP, Schneider RF, Kim H, Lasek-Nesselquist E, McDonough KA*, Agris PF*. Small-molecule antibiotics inhibiting tRNA regulated gene expression is a viable strategy for targeting Gram-positive bacteria. Antimicrob Agents Chemother. 2020; Oct 19 DOI: 10.1128/AAC.01247-20
Girardin RC, McDonough KA. Small RNA Mcr11 requires the transcription factor AbmR for stable expression and regulates genes involved in the central metabolism of Mycobacterium tuberculosis. Mol Microbiol. 2020; 113 (2): 504-520. DOI: 10.1111/mmi.14436
Girardin RC, Bai G, He J, Sui H, McDonough KA. AbmR (Rv1265) is a novel transcription factor of Mycobacterium tuberculosis that regulates host cell association and expression of the non-coding small RNA Mcr11. Mol Microbiol. 2018; 110 (5): 811-830.
Ranganathan, S., J. Cheung, M. Cassidy, C. Ginter, JD Pata and K.A. McDonough. Novel structural features drive DNA binding properties of Cmr, A CRP family protein in TB complex mycobacteria. Nucleic Acids Research. 2018; 46 (1): 403-420.
Johnson, R.M. and K.A. McDonough. Cyclic nucleotide signaling in Mycobacterium tuberculosis: an expanding repertoire. Pathogens and Disease. 2018; 76 (5):
DeMott CM, Girardin R, Cobbert J, Reverdatto S, Burz DS, McDonough K, Shekhtman A. Potent inhibitors of Mycobacterium tuberculosis growth identified by using in-cell NMR-based screening. ACS Chem Biology. 2018; 13 (3): 733-741.
Johnson RM, G. Bai, C.M. DeMott, N.K. Banavali, C.R. Montague, C. Moon, A. Shekhtman, B. VanderVen, K.A. McDonough. Chemical activation of adenylyl cyclase Rv1625c inhibits growth of Mycobacterium tuberculosis on cholesterol and modulates intramacrophage signaling. Mol Microbiology. 2017; 105 (2): 294-308.
Ranganathan, S., G. Bai, A. Lyubetskaya, G.S. Knapp, M.W. Peterson, M. Gazdik, A.L. Gomes, J.E. Galagan and K.A. McDonough. Characterization of an unusual cyclic AMP-responsive transcription factor Rv1675c (Cmr) in TB complex mycobacteria: a global regulator with links to the DosR regulon. Nucleic Acids Research. 2016; 44 (1): 134-151.