Dr. Kreiswirth is the founding director of the PHRI TB Center, a Professor of Medicine at Rutgers and has an adjunct faculty position in the Department of Medicine at New York University, is a senior lecturer at the Mailman School of Public Health at Columbia University and a visiting scientist at the Museum of Natural History. Dr Kreiswirth joined PHRI as a graduate student in 1978 in Dr. Richard Novick’s laboratory working on the molecular biology of Staphylococcus aureus and ultimately cloning and characterizing the genetic determinant responsible for toxic shock syndrome.
In 1992, in response to the New York City tuberculosis outbreaks, the PHRI TB Center was established under Dr. Kreiswirth’s direction as a genotyping laboratory to study the molecular epidemiology of tuberculosis. The center characterized the highly multidrug resistant strain “W” and beginning in 1992 it has genetically characterized over 27,000 M. tuberculosis isolates from global sources. Since its inception, the Center has worked closely with the Centers for Disease Control and Prevention and the New York City and New Jersey Departments of Health to integrate the tools of molecular biology with tuberculosis control efforts. The PHRI TB Center has extended its molecular epidemiological collaborations to global tuberculosis “hotspots” including the Russian prisons, the gold mines in Johannesburg and the XDR outbreak in KwaZulu-Natal, South Africa. Common to all studies is the characterization of drug resistance mutations and correlating phenotypic susceptibility assays with genetic alterations. The molecular epidemiological studies have created a rich genotypic database that has identified highly successful clones that have caused extensive disease throughout the United States and understanding their predominance and their microevolution has become a major effort in the laboratory.
The Kreiswirth laboratory is also focused on nosocomial infections and the emergence of antibiotic resistance and the research aims include the development of rapid genotyping methods for both molecular epidemiologic studies and to advance infection control strategies. The spa typing of S. aureus using the eGenomics analytical software has become a standard method to genotype the species to unravel suspected outbreaks and to determine phylogenetic relatedness. These studies have now established a biological foundation to extend the resolution of genotyping using whole genome sequencing and creating large comparative genomic databases. This work is now ongoing in collaboration with bioinformaticians and curators at the Sackler Institute of Comparative Genomics at the American Museum of Natural History.
The experiences in genotyping M. tuberculosis and S. aureus were brought to the emerging problem of carbapenem resistant Enterobacteriaceae which have rapidly spread across the New York Metropolitan area and which challenge both diagnostic and treatment protocols. In response, the PHRI TB Center has developed rapid molecular beacon-based genotypic assays to both identify and distinguish the predominant carbapenem resistant Klebsiella pneumoniae ST258 and to determine the genetic basis of its resistance. In parallel with the genomic studies to study the phylogeny of S. aureus, we are currently amassing genomic data for K. pneumoniae and the resistance plasmids they harbor to create comparative sequence databases that will be “mined” to create diagnostic platforms and targets for drug and vaccine development.
Simpson G, Zimmerman R, Shashkina E, Chen L, Richard M, Bradford CM, Dragoo GA, Saiers RL, Peloquin CA, Daley CL, Planet P, Narachenia A, Mathema B, Kreiswirth BN (2017) Mycobacterium tuberculosis Infection among Asian Elephants in Captivity. Emerg Infect Dis 23: 513-516. PMI: 28221115
Shah NS, Auld SC, Brust JC, Mathema B, Ismail N, Moodley P, Mlisana K, Allana S, Campbell A, Mthiyane T, Morris N, Mpangase P, van der Meulen H, Omar SV, Brown TS, Narechania A, Shaskina E, Kapwata T, Kreiswirth B, Gandhi NR (2017) Transmission of Extensively Drug-Resistant Tuberculosis in South Africa. N Engl J Med 376: 243-253. PMI: 28099825
Evans SR, Pennello G, Pantoja-Galicia N, Jiang H, Hujer AM, Hujer KM, Manca C, Hill C, Jacobs MR, Chen L, Patel R, Kreiswirth BN, Bonomo RA, Antibacterial Resistance Leadership G (2016) Benefit-risk Evaluation for Diagnostics: A Framework (BED-FRAME). Clin Infect Dis 63: 812-817. PMI: 27193750
Chavda KD, Chen L, Fouts DE, Sutton G, Brinkac L, Jenkins SG, Bonomo RA, Adams MD, Kreiswirth BN (2016) Comprehensive Genome Analysis of Carbapenemase-Producing Enterobacter spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms. MBio 7. PMI: 27965456
Deleo FR, Chen L, Porcella SF, Martens CA, Kobayashi SD, Porter AR, Chavda KD, Jacobs MR, Mathema B, Olsen RJ, Bonomo RA, Musser JM, Kreiswirth BN (2014) Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc Natl Acad Sci U S A 111: 4988-4993. PMI: 24639510
Chen L, Mathema B, Pitout JD, DeLeo FR, Kreiswirth BN (2014) Epidemic Klebsiella pneumoniae ST258 is a hybrid strain. MBio 5: e01355-01314. PMI: 24961694
Farhat MR, Shapiro BJ, Kieser KJ, Sultana R, Jacobson KR, Victor TC, Warren RM, Streicher EM, Calver A, Sloutsky A, Kaur D, Posey JE, Plikaytis B, Oggioni MR, Gardy JL, Johnston JC, Rodrigues M, Tang PK, Kato-Maeda M, Borowsky ML, Muddukrishna B, Kreiswirth BN, Kurepina N, Galagan J, Gagneux S, Birren B, Rubin EJ, Lander ES, Sabeti PC, Murray M (2013) Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat Genet 45: 1183-1189. PMI: 23995135
DeLeo FR, Kennedy AD, Chen L, Bubeck Wardenburg J, Kobayashi SD, Mathema B, Braughton KR, Whitney AR, Villaruz AE, Martens CA, Porcella SF, McGavin MJ, Otto M, Musser JM, Kreiswirth BN (2011) Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. Proc Natl Acad Sci U S A 108: 18091-18096. PMI: 22025717
DeLeo FR, Otto M, Kreiswirth BN, Chambers HF (2010) Community-associated meticillin-resistant Staphylococcus aureus. Lancet 375: 1557-1568. PMI: 20206987
Kennedy AD, Otto M, Braughton KR, Whitney AR, Chen L, Mathema B, Mediavilla JR, Byrne KA, Parkins LD, Tenover FC, Kreiswirth BN, Musser JM, DeLeo FR (2008) Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification. Proc Natl Acad Sci U S A 105: 1327-1332. PMI: 18216255
Gutacker MM, Mathema B, Soini H, Shashkina E, Kreiswirth BN, Graviss EA, Musser JM (2006) Single-nucleotide polymorphism-based population genetic analysis of Mycobacterium tuberculosis strains from 4 geographic sites. J Infect Dis 193: 121-128. PMI: 16323140
Post FA, Willcox PA, Mathema B, Steyn LM, Shean K, Ramaswamy SV, Graviss EA, Shashkina E, Kreiswirth BN, Kaplan G (2004) Genetic polymorphism in Mycobacterium tuberculosis isolates from patients with chronic multidrug-resistant tuberculosis. J Infect Dis 190: 99-106. PMI: 15195248
Gutacker MM, Smoot JC, Migliaccio CA, Ricklefs SM, Hua S, Cousins DV, Graviss EA, Shashkina E, Kreiswirth BN, Musser JM (2002) Genome-wide analysis of synonymous single nucleotide polymorphisms in Mycobacterium tuberculosis complex organisms: resolution of genetic relationships among closely related microbial strains. Genetics 162: 1533-1543. PMI: 12524330
Geng E, Kreiswirth B, Driver C, Li J, Burzynski J, DellaLatta P, LaPaz A, Schluger NW (2002) Changes in the transmission of tuberculosis in New York City from 1990 to 1999. N Engl J Med 346: 1453-1458. PMI: 12000815
Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, Anderson SW, Towell JA, Yuan Y, McMurray DN, Kreiswirth BN, Barry CE, Baker WR (2000) A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 405: 962-966. PMI: 10879539
Roberts RB, de Lencastre A, Eisner W, Severina EP, Shopsin B, Kreiswirth BN, Tomasz A (1998) Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New York hospitals. MRSA Collaborative Study Group. J Infect Dis 178: 164-171. PMI: 9652436
Sreevatsan S, Pan X, Stockbauer KE, Connell ND, Kreiswirth BN, Whittam TS, Musser JM (1997) Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc Natl Acad Sci U S A 94: 9869-9874. PMI: 9275218
Sreevatsan S, Pan X, Stockbauer KE, Williams DL, Kreiswirth BN, Musser JM (1996) Characterization of rpsL and rrs mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from diverse geographic localities. Antimicrob Agents Chemother 40: 1024-1026. PMI: 8849220
Bifani PJ, Plikaytis BB, Kapur V, Stockbauer K, Pan X, Lutfey ML, Moghazeh SL, Eisner W, Daniel TM, Kaplan MH, Crawford JT, Musser JM, Kreiswirth BN (1996) Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family. JAMA 275: 452-457. PMI: 8627966
Sullivan EA, Kreiswirth BN, Palumbo L, Kapur V, Musser JM, Ebrahimzadeh A, Frieden TR (1995) Emergence of fluoroquinolone-resistant tuberculosis in New York City. Lancet 345: 1148-1150. PMI: 7723548
Go ES, Urban C, Burns J, Kreiswirth B, Eisner W, Mariano N, Mosinka-Snipas K, Rahal JJ (1994) Clinical and molecular epidemiology of acinetobacter infections sensitive only to polymyxin B and sulbactam. Lancet 344: 1329-1332. PMI: 7968028
Kreiswirth B, Kornblum J, Arbeit RD, Eisner W, Maslow JN, McGeer A, Low DE, Novick RP (1993) Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus. Science 259: 227-230. PMI: 8093647
Frieden TR, Munsiff SS, Low DE, Willey BM, Williams G, Faur Y, Eisner W, Warren S, Kreiswirth B (1993) Emergence of vancomycin-resistant enterococci in New York City. Lancet 342: 76-79. PMI: 8100912
Berman DS, Eisner W, Kreiswirth B (1993) Community-acquired methicillin-resistant Staphylococcus aureus infection. N Engl J Med 329: 1896. PMI: 8247050
Musser JM, Schlievert PM, Chow AW, Ewan P, Kreiswirth BN, Rosdahl VT, Naidu AS, Witte W, Selander RK (1990) A single clone of Staphylococcus aureus causes the majority of cases of toxic shock syndrome. Proc Natl Acad Sci U S A 87: 225-229. PMI: 1967495
Kreiswirth BN, Lofdahl S, Betley MJ, O’Reilly M, Schlievert PM, Bergdoll MS, Novick RP (1983) The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature 305: 709-712. PMI: 6226876