Center for Global Health Faculty

Academic Degrees

Departmental Address

Contact Information

Email:

petros+jhmi.edu

Phone:

410-502-8233

Fax:

410-614-8173

Link:

Personal Website

Research and Professional Experience

Dr. Karakousis’ primary research interest is the molecular basis of Mycobacterium tuberculosis latency and reactivation. Secondary interests include preclinical screening of novel TB drugs and drug combinations in animal models of caseous necrosis, as well as development of novel molecular assays for the rapid diagnosis of latent TB infection and active TB disease, and for the detection of drug resistance.

Major research activities include studying the adaptation of M. tuberculosis to stress conditions believed to be important in the infected human host, as well as the phenomenon of phenotypic tolerance to antibiotics. In particular, the regulatory cascade involved in the mycobacterial stringent response is under active investigation. Dr. Karakousis, in collaboration with Dr. Joel Bader of the JHU Whiting School of Engineering, has undertaken a systems biology-based approach, including the use of several novel animal models of latency in combination with transcriptional, proteomic, genetic, imaging, and computational techniques, to identify host cytokine networks responsible for immunological control of M. tuberculosis growth, as well as M. tuberculosis regulatory and metabolic pathways required for bacillary growth restriction and reactivation.

The guinea pig model of TB, which forms necrotic lesions histologically resembling its human counterparts, is also being used to study the sterilizing activity of novel drugs and drug combinations against persisters, with the ultimate goal of shortening antituberculous chemotherapy. Molecular assays using blood, sputum, and urine samples are being investigated with the goal of developing rapid, sensitive, and specific point-of-care tests for TB diagnosis and detection of drug resistance. In collaboration with the Gorgas Memorial Institute of Health Studies (ICGES) in Panama, the sensitivity and specificity of Multiplex Allele-Specific PCR (MAS-PCR) is being studied for the rapid detection of isoniazid and rifampin resistance in archived, MDR-TB clinical isolates.

Keywords

Mycobacterium tuberculosis, latency, persistence, gene regulation, drug resistance, animal models, chemotherapy, diagnosis

Honors and Awards

2009 Basic Research Junior Faculty Award, JHU Dept. of Medicine 2005 Arthur M. Dannenberg, Jr. Award for Postdoctoral Research, JHU Center for TB Research 2001 Edward W. Holmes Resident Research Award, Dept. of Medicine, University of Pennsylvania School of Medicine 2000 Maurice F. Attie Resident Teaching Award, Dept. of Medicine, University of Pennsylvania School of Medicine 1998 Alpha Omega Alpha Honor Medical Society 1998 Missouri State Medical Association Award 1994 Distinguished Alumni Scholarship (full-tuition academic scholarship at Washington University School of Medicine) 1994 Phi Beta Kappa Society

Selected Publications

1. Ahmad Z, Nuermberger EL, Tasneen R, Pinn ML, Williams KN, Peloquin CA, Grosset J, Karakousis PC. Comparison of the ‘Denver regimen’ against acute tuberculosis in the mouse and guinea pig. J Antimicrob Chemother. 2010;65:729-34.
2. Converse PJ, Eisenach KD, Theus SA, Nuermberger EL, Tyagi S, Ly LH, Geiman DE, Guo H, Nolan ST, Akar NC, Klinkenberg LG, Gupta R, Lun S, Karakousis PC, Lamichhane G, McMurray DN, Grosset JH, Bishai WR. The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models. PLoS One. 2010;5:e10289.  
3. Cutrufello NJ, Karakousis PC, Fishler J, Albini TA. Intraocular tuberculosis. Ocul Immunol Inflamm. 2010;18:281-91.
4. Ahmad Z, Pinn ML, Nuermberger EL, Peloquin CA, Grosset J, Karakousis PC. The potent bactericidal activity of streptomycin in the guinea pig model of tuberculosis ceases due to the presence of persisters. J Antimicrob Chemother.2010;65:2172-5.
5. Klinkenberg LG, Lee J-H, Bishai WR, Karakousis PC. The stringent response is required for full virulence of Mycobacterium tuberculosis in guinea pigs. J Infect Dis. 2010;202:1397-1404.
6. Piggott D, Karakousis PC. Timing of antiretroviral therapy for HIV in the setting of TB treatment. Clin Dev Immunol. 2011;2011:103917.
7. Zhou A, Nawaz M, Xue X, Karakousis PC, Yao Y, Xu J. Molecular genotyping of Mycobacterium tuberculosis in Xi'an, China using MIRU-VNTR typing system. Int J Tuberc Lung Dis. 2011;15:517-22.
8. Ahmad Z, Fraig MM, Bisson GP, Nuermberger EL, Grosset JH, Karakousis PC. Dose-dependent activity of pyrazinamide in animal models of intracellular and extracellular tuberculosis. Antimicrob Agents Chemother. 2011;55:1527-32.
9. Ahmad Z, Fraig MM, Pinn ML, Tyagi S, Nuermberger EL, Grosset JH, Karakousis PC. Effectiveness of tuberculosis chemotherapy correlates with resistance to Mycobacterium tuberculosis infection in animal models. J Antimicrob Chemother. 2011;66:1560-6.
10. Dutta NK, Mazumdar K, Dastidar SG, Karakousis PC, Amaral L. New Patentable Use of an Old Neuroleptic Compound Thioridazine to Combat Tuberculosis: A Gene Regulation Perspective. Recent Pat Antiinfect Drug Discov. 2011;6:128-38.
11. Abomoelak B, Ward SK, Marcus S, Karakousis PC, Steinberg H, Talaat AM. Characterization of a novel heat shock protein (Hsp22.5) involved in the pathogenesis of Mycobacterium tuberculosis. J Bacteriol. 2011;193:3497-505.
12. Be NA, Klinkenberg LG, Bishai WR, Karakousis PC, Jain SK. Strain-dependent CNS dissemination in guinea pigs after Mycobacterium tuberculosis aerosol challenge. Tuberculosis (Edinb). 2011;91:386-9.
13. Thayil SM, Morrison N, Schechter N, Rubin H, Karakousis PC. The role of the novel exopolyphosphatase MT0516 in Mycobacterium tuberculosis drug tolerance and persistence. PLoS One. 2011;6:e28076.
14. Thayil SM, Albini TA, Nazari H, Moshfeghi AA, Parel J-MA, Rao NA, Karakousis PC. Local Ischemia and Increased Expression of Vascular Endothelial Growth Factor Following Ocular Dissemination of Mycobacterium tuberculosis. PLoS One. 2011;6:e28383.