Karakousis, Petros C., M.D.

Petros Karakousis, M.D.

Associate Professor of Medicine
Division of Infectious Diseases

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.

Dr. Karakousis received his undergraduate degree in 1994 from the Johns Hopkins University and his medical degree in 1998 from Washington University School of Medicine in St. Louis.  He completed residency training in Internal Medicine in 2001 at the Hospital of the University of Pennsylvania.  After completing fellowship training in Infectious Diseases at Johns Hopkins University School of Medicine, he joined the Department of Medicine faculty in 2005.

Business Address:

Center for Tuberculosis Research
Dept. of Medicine, Div. of Infectious Diseases
Johns Hopkins University School of Medicine
1550 Orleans St., Room 110
Baltimore, MD 21231                                      
Tel: 410-502-8233
Fax: 410-614-8173
E-mail: petros@jhmi.edu

Publications: To read some of these publications online, click here. Please note that to read the full text of some of these articles requires that you have an online subscription to the journal.

Selected Peer-reviewed articles:

1. Canning BJ, Undem BJ, Karakousis PC, Dey RD. Effects of organotypic culture on parasympathetic innervation of guinea pig trachealis. Am J Physiol. 1996; 271:L698-L706.

2. Karakousis PC, John SK, Behling KC , Surace EM, Smith JE, Hendrickson A, Tang W-X, Bennett J, Milam AH. Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues. Mol Vis. 2001; 7:154-163.

3. Karakousis PC, Page KR, Varello MA, Howlett PJ, Stieritz DD. Waterhouse-Friderichsen syndrome after infection with Group A streptococcus. Mayo Clin Proc. 2001;76:1167-1170.

4. Page KR, Karakousis PC, Maslow J. Postoperative pneumococcal cellulitis in systemic lupus erythematosus. Scand J Infect. Dis. 2003; 35:141-3.

5. Coppola AG, Karakousis PC, Metz DC, Go MF, Mhokashi M, Howden CW, Raufman JP, Sharma VK. Hepatitis C knowledge among primary care residents: is our teaching adequate for the times? Am J Gastroenterol. 2004; 99:1720-5.

6. Karakousis PC, Moore RD, Chaisson RE. Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy. Lancet Infect Dis. 2004; 4:557-65.

7. Karakousis PC, Bishai WR, Dorman SE. Mycobacterium tuberculosis cell envelope lipids and the host immune response. Cell Microbiol. 2004; 6:105-116.

8. Karakousis PC, Yoshimatsu T, Lamichhane L, Woolwine SC, Nuermberger EL, Grosset J, Bishai WR. Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artificial granulomas in mice. J Exp Med. 2004; 200:647-57.

9. Karakousis PC, Trucksis M, Dumler JS. Chronic Q fever in the United States. J Clin Microbiol. 2006;44:2283-7.

10. Brastianos PK, Swanson J, Torbenson M, Sperati J, Karakousis PC. Tuberculosis-associated hemophagocytic syndrome. Lancet Infect. Dis. 2006;6:447-54.

11. Karakousis PC, Sifakis FG, Montes de Oca R, Amorosa VC, Page, KR, Manabe YC, Campbell J. Medical resident familiarity with national tuberculosis guidelines. BMC Infect Dis. 2007;7:89.

12. Riddell J 4th, Kaul DR, Karakousis PC, Gallant JE, Mitty J, Kazanjian PH. Mycobacterium avium complex immune reconstitution inflammatory syndrome: Long term outcomes. J Transl Med. 2007;5:50.

13. Jain SK, Hernandez-Abanto, Cheng Q-J, Singh P, Ly LH, Klinkenberg LG, Morrison NE, Converse PJ, Nuermberger EL, Grosset J, McMurray DN, Karakousis PC, Lamichhane G, Bishai WR. Accelerated detection of Mycobacterium tuberculosis genes essential for bacterial survival in guinea pigs compared with mice. J Infect Dis. 2007;195:1634-42.

14. Williams EP, Lee JH, Bishai WR, Colantuoni C, Karakousis PC. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J Bacteriol. 2007;189:4234-42.

15. Lee, J-H, Karakousis PC, Bishai WR. Characterization of sigma factor regulation in Mycobacterium tuberculosis by SigB and SigF. J Bacteriol. 2008;190:699-707.

16. Karakousis PC, Williams EP, Bishai WR. Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis. J Antimicrob Chemother. 2008;61:323-31.

17. Klinkenberg L, Sutherland L, Bishai WR, Karakousis PC. Metronidazole lacks activity against Mycobacterium tuberculosis in an in vivo hypoxic granuloma model of latency. J Infect Dis. 2008;198:275-83.

18. Albini TA, Karakousis PC, Rao NA. Interferon-gamma release assays in the diagnosis of tuberculous uveitis. Am J Ophthalmol. 2008;146:486-8.

19. Converse PJ, Karakousis PC, Klinkenberg LG, Kesavan AK, Ly LH, Allen SS, Grosset JH, Jain SK, Lamichhane G, Manabe YC, McMurray DN, Nuermberger EL, Bishai WR. The role of the DosR/DosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models. Infect. Immun. 2009;77:1230-37.

20. Rifat D, Bishai WR, Karakousis PC. Phosphate depletion: A novel trigger for Mycobacterium tuberculosis persistence. J Infect Dis. 2009;200:1126-35.

21. Ahmad Z, Klinkenberg LG, Pinn ML , Fraig MM, Peloquin CA, Bishai WR, Nuermberger EL, Grosset J, Karakousis PC. Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig. J Infect Dis. 2009;200:1136-43.

22. Rao NA, Albini TA, Kumaradas M, Pinn ML, Fraig MM, Karakousis PC. Experimental ocular tuberculosis in guinea pigs. Arch. Ophthalmol. 2009;127:1162-6.

23. 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.

24. 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.

25. Cutrufello NJ, Karakousis PC, Fishler J, Albini TA. Intraocular tuberculosis. Ocul Immunol Inflamm. 2010;18:281-91.

26. 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.

27. 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.

28. Piggott D, Karakousis PC. Timing of antiretroviral therapy for HIV in the setting of TB treatment. Clin Dev Immunol. 2011;2011:103917.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

Book Chapters:

Karakousis PC, Chaisson RE. Mycobacterial infections and HIV infection. In: Fishman's Pulmonary Diseases and Disorders, 4th edition, Fishman AP, Elias JA, Fishman JA, Grippi MA, Senior RM, Pack AI, ed. New York: McGraw Hill, 2008:2487-2497.

Karakousis PC. Mechanisms of Action and Resistance of the Antimycobacterial Agents. In: Antimicrobial Drug Resistance, Mayers D, ed. New York: Humana Press, 2009:271-291

Kolyva A, Karakousis PC. Old and New TB Drugs: Mechanisms of Action and Resistance. In: Mycobacterium tuberculosis/Book 2, Cardona P-J, ed. InTech, 2011.