Research Summary

The Kreiswirth lab is home to the PHRI Tuberculosis Center and the PHRI Hospital Infections Program. In 2002, the PHRI TB Center continued a joint project with New York Hospital Queens Medical Center and Merck, Inc. to genotype staphylococcal isolates in order to look at staphylococcal gene expression in primary infections. Genotyping and evolutionary studies on Mycobacterium tuberculosis remain a major effort in the laboratory. The new Biosafety Level 3 facilities at the International Center for Public Health have greatly enhanced this research. The genetically characterized strain collection now exceeds 16,000 isolates of M. tuberculosis, of which over 3,000 are multidrug resistant. The Kreiswirth lab genotyped the recent 2001 strain collection from all New York City tuberculosis cases on the basis of four molecular techniques, including single nucleotide polymorphisms. The nucleotide changes have proven to be a powerful method to distinguish the species into a genetic tree with eight distinct branches or clusters. They are currently mapping suspected virulence determinants along this evolutionary tree to understand the pathogenic make-up of M. tuberculosis.

The Center also continued to extend its work on sequencing a repeat region in the protein A gene (spa typing) to differentiate Staphylococcus aureus strains and the general use of variable number tandem repeats (VNTR) to genotype bacteria. The Kreiswirth lab analyzed another repeat region of clumping factor B gene (clfB) as a secondary target to discriminate strains grouped by spa typing and novel VNTR sequences in Pseudomonas aeruginosa. In addition, they are currently evaluating Enterococcus faecalis and faecium genes for their ability to differentiate these species.

The Hospital Infections Program, which includes the Molecular Outbreak Center and a Surveillance database, was launched in April 2002 as a statewide program in New Jersey to assist hospitals and the community in controlling hospital-acquired and community-based infections. The Outbreak Center has done crucial work in characterizing community-onset methicillin-resistant S. aureus strains from both prevalence studies and incidence cases. On the basis of this work, the Kreiswirth lab developed surveillance and research collaborations with the Centers for Disease Control, the National Institutes of Health, Americans For AIDS Research and the New York City Department of Health.




Recent Articles

Reed MB, Domenech P, Manca C, Su H, Barczak AK, Kreiswirth BN, Kaplan G, Barry CE 3rd. (2004).
A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response.
Nature. 2004 Sep 2;431(7004):84-7
PMID: 15343336
Abstract  |  Full Article

Manca C, Reed MB, Freeman S, Mathema B, Kreiswirth B, Barry CE 3rd, Kaplan G. (2004).
Differential monocyte activation underlies strain-specific Mycobacterium tuberculosis pathogenesis.
Infect Immun. 2004 Sep;72(9):5511-4
PMID: 15322056
Abstract  |  Full Article

O'Brien FG, Lim TT, Chong FN, Coombs GW, Enright MC, Robinson DA, Monk A, Said-Salim B, Kreiswirth BN, Grubb WB. (2004).
Diversity among community isolates of methicillin-resistant Staphylococcus aureus in Australia.
J Clin Microbiol. 2004 Jul;42(7):3185-90
PMID: 15243080
Abstract  |  Full Article

Shopsin B, Zhao X, Kreiswirth BN, Tillotson GS, Drlica K. (2004).
Are the new quinolones appropriate treatment for community-acquired methicillin-resistant Staphylococcus aureus?
Int J Antimicrob Agents. 2004 Jul;24(1):32-4
PMID: 15225857
Abstract  |  Full Article

Charlebois ED, Perdreau-Remington F, Kreiswirth B, Bangsberg DR, Ciccarone D, Diep BA, Ng VL, Chansky K, Edlin B, Chambers HF. (2004).
Origins of community strains of methicillin-resistant Staphylococcus aureus.
Clin Infect Dis. 2004 Jul 1;39(1):47-54. Epub 2004 Jun 01
PMID: 15206052
Abstract  |  Full Article

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. 2004 Jul 1;190(1):99-106. Epub 2004 May 28
PMID: 15195248
Abstract  |  Full Article

Milan SJ, Hauge KA, Kurepina NE, Lofy KH, Goldberg SV, Narita M, Nolan CM, McElroy PD, Kreiswirth BN, Cangelosi GA. (2004).
Expanded geographical distribution of the N family of Mycobacterium tuberculosis strains within the United States.
J Clin Microbiol. 2004 Mar;42(3):1064-8
PMID: 15004054
Abstract  |  Full Article

Koreen L, Ramaswamy SV, Graviss EA, Naidich S, Musser JM, Kreiswirth BN. (2004).
spa typing method for discriminating among Staphylococcus aureus isolates: implications for use of a single marker to detect genetic micro- and macrovariation.
J Clin Microbiol. 2004 Feb;42(2):792-9
PMID: 14766855
Abstract  |  Full Article

Kaplan G, Post FA, Moreira AL, Wainwright H, Kreiswirth BN, Tanverdi M, Mathema B, Ramaswamy SV, Walther G, Steyn LM, Barry CE 3rd, Bekker LG. (2003).
Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity.
Infect Immun. 2003 Dec;71(12):7099-108
PMID: 14638800
Abstract  |  Full Article

Huard RC, Chitale S, Leung M, Lazzarini LC, Zhu H, Shashkina E, Laal S, Conde MB, Kritski AL, Belisle JT, Kreiswirth BN, Lapa e Silva JR, Ho JL. (2003).
The Mycobacterium tuberculosis complex-restricted gene cfp32 encodes an expressed protein that is detectable in tuberculosis patients and is positively correlated with pulmonary interleukin-10.
Infect Immun. 2003 Dec;71(12):6871-83
PMID: 14638775
Abstract  |  Full Article

Saiman L, O'Keefe M, Graham PL 3rd, Wu F, Said-Salim B, Kreiswirth B, LaSala A, Schlievert PM, Della-Latta P. (2003).
Hospital transmission of community-acquired methicillin-resistant Staphylococcus aureus among postpartum women.
Clin Infect Dis. 2003 Nov 15;37(10):1313-9. Epub 2003 Oct 17
PMID: 14583864
Abstract  |  Full Article

Wang XM, Noble L, Kreiswirth BN, Eisner W, McClements W, Jansen KU, Anderson AS. (2003).
Evaluation of a multilocus sequence typing system for Staphylococcus epidermidis.
J Med Microbiol. 2003 Nov;52(11):989-998
PMID: 14532344
Abstract

Shopsin B, Herring S, Kreiswirth BN. (2003).
Hospital-acquired and community-derived: the future of MRSA?
Clin Infect Dis. 2003 Jul 1;37(1):151-2; author reply 152
PMID: 12830425

Somerville GA, Said-Salim B, Wickman JM, Raffel SJ, Kreiswirth BN, Musser JM. (2003).
Correlation of acetate catabolism and growth yield in Staphylococcus aureus: implications for host-pathogen interactions.
Infect Immun. 2003 Aug;71(8):4724-32
PMID: 12874354
Abstract  |  Full Article

Rad ME, Bifani P, Martin C, Kremer K, Samper S, Rauzier J, Kreiswirth B, Blazquez J, Jouan M, van Soolingen D, Gicquel B. (2003).
Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family.
Emerg Infect Dis. 2003 Jul;9(7):838-45
PMID: 12890325
Abstract  |  Full Article

Munsiff SS, Nivin B, Sacajiu G, Mathema B, Bifani P, Kreiswirth BN. (2003).
Persistence of a highly resistant strain of tuberculosis in New York City during 1990-1999.
J Infect Dis. 2003 Aug 1;188(3):356-63. Epub 2003 Jul 18
PMID: 12870116
Abstract  |  Full Article

Said-Salim B, Mathema B, Kreiswirth BN. (2003).
Community-acquired methicillin-resistant Staphylococcus aureus: an emerging pathogen.
Infect Control Hosp Epidemiol. 2003 June;24(6):451-455
PMID: 12828324
Abstract

Kuo MR, Morbidoni HR, Alland D, Sneddon SF, Gourlie BB, Staveski MM, Leonard M, Gregory JS, Janjigian AD, Yee C, Musser JM, Kreiswirth B, Iwamoto H, Perozzo R, Jacobs WR Jr, Sacchettini JC, Fidock DA. (2003).
Targeting tuberculosis and malaria through inhibition of Enoyl reductase: compound activity and structural data.
J Biol Chem. 2003 Jun 6;278(23):20851-9. Epub 2003 Feb 26
PMID: 12606558
Abstract  |  Full Article

Saiman L, Cronquist A, Wu F, Zhou J, Rubenstein D, Eisner W, Kreiswirth BN, Della-Latta P. (2003).
An outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.
Infect Control Hosp Epidemiol. 2003 May;24(5):317-21
PMID: 12785403
Abstract

Filliol I, Driscoll JR, van Soolingen D, Kreiswirth BN, Kremer K, Valetudie G, Dang DA, Barlow R, Banerjee D, Bifani PJ, Brudey K, Cataldi A, Cooksey RC, Cousins DV, Dale JW, Dellagostin OA, Drobniewski F, Engelmann G, Ferdinand S, Gascoyne-Binzi D, Gordon M, Gutierrez MC, Haas WH, Heersma H, Kassa-Kelembho E, Ho ML, Makristathis A, Mammina C, Martin G, Mostrom P, Mokrousov I, Narbonne V, Narvskaya O, Nastasi A, Niobe-Eyangoh SN, Pape JW, Rasolofo-Razanamparany V, Ridell M, Rossetti ML, Stauffer F, Suffys PN, Takiff H, Texier-Maugein J, Vincent V, de Waard JH, Sola C, Rastogi N. (2003).
Snapshot of moving and expanding clones of Mycobacterium tuberculosis and their global distribution assessed by spoligotyping in an international study.
J Clin Microbiol. 2003 May;41(5):1963-70
PMID: 12734235
Abstract  |  Full Article

Rosato AE, Kreiswirth BN, Craig WA, Eisner W, Climo MW, Archer GL. (2003).
mecA-blaZ corepressors in clinical Staphylococcus aureus isolates.
Antimicrob Agents Chemother 2003 Apr;47(4):1460-3
PMID: 12654694
Abstract  |  Full Article

Zhao X, Eisner W, Perl-Rosenthal N, Kreiswirth B, Drlica K. (2003).
Mutant prevention concentration of garenoxacin (BMS-284756) for ciprofloxacin-susceptible or -resistant Staphylococcus aureus.
Antimicrob Agents Chemother. 2003 Mar;47(3):1023-7
PMID: 12604537
Abstract  |  Full Article

Mathema, B., Kreiswirth, B.N. (2003).
Rethinking tuberculosis epidemiology: the utility of Molecular methods.
ASM News. 2003 Feb;69(2):80-85

Fey PD, Said-Salim B, Rupp ME, Hinrichs SH, Boxrud DJ, Davis CC, Kreiswirth BN, Schlievert PM. (2003).
Comparative molecular analysis of community- or hospital-acquired methicillin-resistant Staphylococcus aureus.
Antimicrob Agents Chemother. 2003 Jan;47(1):196-203
PMID: 12499191
Abstract  |  Full Article

Shopsin B, Mathema B, Alcabes P, Said-Salim B, Lina G, Matsuka A, Martinez J, Kreiswirth BN. (2003).
Prevalence of agr specificity groups among Staphylococcus aureus strains colonizing children and their guardians.
J Clin Microbiol 2003 Jan;41(1):456-9
PMID: 12517893
Abstract  |  Full Article

Said-Salim B, Dunman PM, McAleese FM, Macapagal D, Murphy E, McNamara PJ, Arvidson S, Foster TJ, Projan SJ, Kreiswirth BN. (2003).
Global regulation of Staphylococcus aureus genes by Rot.
J Bacteriol 2003 Jan;185(2):610-9
PMID: 12511508
Abstract  |  Full Article

Tazi L, Kreiswirth B, Carriere C, Tibayrenc M. (2002).
Molecular epidemiology of Mycobacterium tuberculosis and its relevance to the surveillance and control of TB: an e-debate.
Infect Genet Evol. 2002 Dec;2(2):153-8
PMID: 12797993
Full Article

McElroy PD, Sterling TR, Driver CR, Kreiswirth B, Woodley CL, Cronin WA, Hardge DX, Shilkret KL, Ridzon R. (2002).
Use of DNA fingerprinting to investigate a multiyear, multistate tuberculosis outbreak.
Emerg Infect Dis. 2002 Nov;8(11):1252-6
PMID: 12453351
Abstract  |  Full Article

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 2002 Dec;162(4):1533-43
PMID: 12524330
Abstract  |  Full Article

Filliol I, Driscoll JR, Van Soolingen D, Kreiswirth BN, Kremer K, Valetudie G, Anh DD, Barlow R, Banerjee D, Bifani PJ, Brudey K, Cataldi A, Cooksey RC, Cousins DV, Dale JW, Dellagostin OA, Drobniewski F, Engelmann G, Ferdinand S, Gascoyne-Binzi D, Gordon M, Gutierrez MC, Haas WH, Heersma H, Kallenius G, Kassa-Kelembho E, Koivula T, Ly HM, Makristathis A, Mammina C, Martin G, Mostrom P, Mokrousov I, Narbonne V, Narvskaya O, Nastasi A, Niobe-Eyangoh SN, Pape JW, Rasolofo-Razanamparany V, Ridell M, Rossetti ML, Stauffer F, Suffys PN, Takiff H, Texier-Maugein J, Vincent V, De Waard JH, Sola C, Rastogi N. (2002).
Global distribution of Mycobacterium tuberculosis spoligotypes.
Emerg Infect Dis 2002 Nov;8(11):1347-9
PMID: 12453368
Abstract  |  Full Article

Driscoll JR, Bifani PJ, Mathema B, McGarry MA, Zickas GM, Kreiswirth BN, Taber HW.
Spoligologos: a bioinformatic approach to displaying and analyzing Mycobacterium tuberculosis data. (2002).
Emerg Infect Dis 2002 Nov;8(11):1306-9
PMID: 12453361
Abstract  |  Full Article

Munsiff SS, Bassoff T, Nivin B, Li J, Sharma A, Bifani P, Mathema B, Driscoll J, Kreiswirth BN. (2002).
Molecular epidemiology of multidrug-resistant tuberculosis, New York City, 1995-1997.
Emerg Infect Dis 2002 Nov;8(11):1230-8
PMID: 12453347
Abstract  |  Full Article

Low DE, Kreiswirth BN, Weiss K, Willey BM. (2002).
Activity of GAR-936 and other antimicrobial agents against North American isolates of Staphylococcus aureus.
Int J Antimicrob Agents 2002 Sep;20(3):220-2
PMID: 12385702
Abstract  |  Full Article

Dziadek J, Rajagopalan M, Parish T, Kurepina N, Greendyke R, Kreiswirth BN, Madiraju MV. (2002).
Mutations in the CCGTTCACA DnaA box of Mycobacterium tuberculosis oriC that abolish replication of oriC plasmids are tolerated on the chromosome.
J Bacteriol 2002 Jul;184(14):3848-55
PMID: 12081955
Abstract  |  Full Article

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 2002 May 9;346(19):1453-8
PMID: 12000815
Abstract

Bifani PJ, Mathema B, Kurepina NE, Kreiswirth BN. (2002).
Strain families of Mycobacterium tuberculosis.
Trends Microbiol 2002 Apr;10(4):168
PMID: 11912021
Full Article

Low DE, Muller M, Duncan CL, Willey BM, de Azavedo JC, McGeer A, Kreiswirth BN, Pong-Porter S, Bast DJ. (2002).
Activity of BMS-284756, a novel des-fluoro(6) quinolone, against Staphylococcus aureus, including contributions of mutations to quinolone resistance.
Antimicrob Agents Chemother 2002 Apr;46(4):1119-21
PMID: 11897603
Abstract  |  Full Article

Mathema B, Bifani PJ, Driscoll J, Steinlein L, Kurepina N, Moghazeh SL, Shashkina E, Marras SA, Campbell S, Mangura B, Shilkret K, Crawford JT, Frothingham R, Kreiswirth BN. (2002).
Identification and evolution of an IS6110 low-copy-number Mycobacterium tuberculosis cluster.
J Infect Dis 2002 Mar 1;185(5):641-9
PMID: 11865421
Abstract  |  Full Article

Bifani PJ, Mathema B, Kurepina NE, Kreiswirth BN. (2002).
Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains.
Trends Microbiol 2002 Jan;10(1):45-52
PMID: 11755085
Abstract  |  Full Article

Kubin M, Fridrichovska E, Kozakova B, Zdrazilek J, Kreiswirth B. (2001).
Human transmission of tuberculosis confirmed by DNA fingerprinting
Epidemiol Mikrobiol Imunol 2001 Nov;50(4):157-9
PMID: 11769177
Abstract

Bifani P, Mathema B, Campo M, Moghazeh S, Nivin B, Shashkina E, Driscoll J, Munsiff SS, Frothingham R, Kreiswirth BN. (2001).
Molecular identification of streptomycin monoresistant Mycobacterium tuberculosis related to multidrug-resistant W strain.
Emerg Infect Dis 2001 Sep-Oct;7(5):842-8
PMID: 11747697
Abstract  |  Full Article

Magnani J, Mathema B, Berger J, Brown S, David M, Glatt A, Pujol F, Segal-Maurer S, Riley LW, Kreiswirth BN, Sepkowitz KA; TBNetwork. (2001).
Molecular epidemiology of tuberculosis among eight hospitals in New York City, 1996-1997.
Int J Infect Dis 2001;5(3):126-32
PMID: 11724668
Abstract

Johnson S, Brusasca P, Lyashchenko K, Spencer JS, Wiker HG, Bifani P, Shashkina E, Kreiswirth B, Harboe M, Schluger N, Gomez M, Gennaro ML (2001).
Characterization of the secreted MPT53 antigen of Mycobacterium tuberculosis.
Infect Immun 2001 Sep;69(9):5936-9
PMID: 11500477
Abstract  |  Full Article

Shopsin B, Kreiswirth BN (2001).
Molecular epidemiology of methicillin-resistant Staphylococcus aureus.
Emerg Infect Dis 2001 Mar-Apr;7(2):323-6
PMID: 11294733
Abstract  |  Full Article

Kato-Maeda M, Bifani PJ, Kreiswirth BN, Small PM. (2001).
The nature and consequence of genetic variability within Mycobacterium tuberculosis.
J Clin Invest 2001 Mar;107(5):533-7
PMID: 11238552
Full Article

Waddell RD, Lishimpi K, von Reyn CF, Chintu C, Baboo KS, Kreiswirth B, Talbot EA, Karagas MR; Dartmouth/UCLMS/UNZA Collaborative Study Group. (2001).
Bacteremia due to Mycobacterium tuberculosis or M. bovis, Bacille Calmette-Guerin (BCG) among HIV- positive children and adults in Zambia.
AIDS 2001 Jan 5;15(1):55-60
PMID: 11192868
Abstract  |  Full Article



Kreiswirth, B.N., Kornblum, J., Arbeit, R., Eisner, W., Maslow, J., McGeer, A., Low D., and Novick, R.P. (1993).
Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus.
Science 259:227-230.

Freiden, T.R., Musiff, S.S., Low, D.E., Willey, B.M., Williams, G., Faur, Y, Eisner, W., Warren, S., and Kreiswirth, B.N. (1993).
Emergence of vancomycin-resistant enterococci in New York City.
Lancet, 342:76-79.

Takiff, H.E., Salazar, L., Guerrero, C., Philipp, W., Huang, W.M., Kreiswirth, B.N., Cole, S.T., Jacobs, W.R., and Telenta, A. (1994).
Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations.
Antimicrob. Agents Chemother. 38:773-780.

Kapur, V., Li, L.L., Iordanescu, S., Hamrick, M.R., Wanger, A., Kreiswirth, B.N. and Musser, J.M. (1994).
Characterization by automated DNA sequencing of mutations in the gene, rpoB, encoding the RNA polymerase b subunit in rifampin-resistant Mycobacterium tuberculosis strains from New York City and Texas.
J. Clin. Microb. 32:1095-1098.

Bifani, P.J., Plikaytis, B.B., Kapur, V., Stockbauer, K., Pan, X., Lutfey, M., Moghazeh, S., Eisner, W., Daniel, T. Kaplan, M., Crawford, J., Musser, J. M. and Kreiswirth B.N. (1996).
Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family.
JAMA 275:452-457.

Lutfey, M., Della-Latta, P., Kapur, V., Palumbo, L.A., Gurner, D., Stotzky, G., Brudney, K., Dobkin, J., Moss, A., Musser, J.M. and Kreiswirth, B.N. (1996).
Independent origin of mono-rifampin-resistant Mycobacterium tuberculosis in patients with AIDS.
Am. J. Respir. Crit. Care Med. 153:837-840.

PubMed Lisitings>




C.V.

Ph.D. Hamilton College, B.A., 1976; University of Western Ontario, Research Fellow, 1977-1979; New York University, Ph.D., 1986; PHRI, Post Doc., 1986-1988; PHRI, Research Scientist, 1988-1990; New York City Department of Health Phage and Typing and Antibiotic Susceptibility Testing Laboratory, Chief, 1990-1992; PHRI TB Center, Director, 1992-present; NYU School of Medicine, Adjunct Assistant Professor of Medicine, 1994-present.