In vitro properties of antimicrobial bromotyrosine alkaloids

Journal of Medical Microbiology - Tập 55 Số 4 - Trang 407-415 - 2006
Neora Pick1, Mamta Rawat2,1, Dorit Arad1, Jiong Lan3, Junfa Fan3, Andrew S. Kende3, Yossef Av‐Gay1
1Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada
2Department of Biology, California State University – Fresno, Fresno, CA 937401, USA
3Department of Chemistry, University of Rochester, Rochester, NY 14627-0216, USA

Tóm tắt

A bromotyrosine alkaloid family of antimicrobial agents was synthesized using the known structure of a natural inhibitor of the mycobacterial mycothiolS-conjugate amidase (MCA) as a template. This series of compounds represents a novel class of anti-infective agents against Gram-positive pathogens, including mycobacteria and meticillin- and vancomycin-resistantStaphylococcus aureus. The fact that these compounds are active against mycobacterial strains in which the MCA gene is deleted and against Gram-positive bacteria lacking mycothiol suggests the existence of an alternative target for these compounds. One member of this family, EXEG1706, was identified as the lead compound possessing low MICs (2·5–25 μg ml−1) for several clinical isolates, whilst having low toxicity for THP-1 monocytes and macrophages.

Từ khóa


Tài liệu tham khảo

Arad, 2003, Antimicrobial compounds against Staphylococci, Mycobacteria and other infectious agents

Bartley, 2002, First case of VRSA identified in Michigan, Infect Control Hosp Epidemiol, 23, 480, 10.1017/S0195941700082333

Basta, 1999, Modulation of monocytic cell activity and virus susceptibility during differentiation into macrophages, J Immunol, 162, 3961, 10.4049/jimmunol.162.7.3961

Casewell, 1986, The carrier state: methicillin-resistant Staphylococcus aureus, J Antimicrob Chemother, 18 (Suppl. A), 1, 10.1093/jac/18.Supplement_A.1

Cassone, 2004, Identification of a variant “Rome clone” of methicillin-resistant Staphylococcus aureus with decreased susceptibility to vancomycin, responsible for an outbreak in an intensive care unit, Microb Drug Resist, 10, 43, 10.1089/107662904323047790

Coccia, 1999, STAT1 activation during monocyte to macrophage maturation: role of adhesion molecules, Int Immunol, 11, 1075, 10.1093/intimm/11.7.1075

Dye, 1999, Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project, . JAMA, 282, 677, 10.1001/jama.282.7.677

Gessani, 1993, & 7 other authors, . J Immunol, 151, 3758, 10.4049/jimmunol.151.7.3758

Kende, 2004, Total synthesis of a dibromotyrosine alkaloid inhibitor of mycothiol S-conjugate amidase, Tetrahedron Lett, 45, 133, 10.1016/j.tetlet.2003.10.117

Kluytmans, 1995, Nasal carriage of Staphylococcus aureus as a major risk factor for wound infections after cardiac surgery, J Infect Dis, 171, 216, 10.1093/infdis/171.1.216

Lowy, 1998, Staphylococcus aureus infections, N Engl J Med, 339, 520, 10.1056/NEJM199808203390806

Mallaval, 2004, & 7 other authors, Clin Microbiol Infect, 10, 459, 10.1111/j.1469-0691.2004.00878.x

Maynes, 2003, The crystal structure of 1-d- myo -inosityl 2-acetamido-2-deoxy- α -d-glucopyranoside deacetylase (MshB) from Mycobacterium tuberculosis reveals a zinc hydrolase with a lactate dehydrogenase fold, J Biol Chem, 278, 47166, 10.1074/jbc.M308914200

McCarthy, 2003, Crystallization and preliminary X-ray analysis of N -acetyl-1-d- myo -inosityl-2-deoxy- α -d-glucopyranoside deacetylase (MshB) from Mycobacterium tuberculosis, Acta Crystallogr D Biol Crystallogr, 59, 2316, 10.1107/S0907444903020961

1993, National Committee for Clinical Laboratory Standards

Negi, 2003, Drug resistance in tuberculosis in Delhi: a 2 year profile (2001–2002), J Commun Dis, 35, 74

Newton, 1996, & 7 other authors, J Bacteriol, 178, 1990, 10.1128/JB.178.7.1990-1995.1996

Newton, 2000, A novel mycothiol-dependent detoxification pathway in mycobacteria involving mycothiol S -conjugate amidase, Biochemistry, 39, 10739, 10.1021/bi000356n

Nicholas, 2001, Novel bromotyrosine alkaloids: inhibitors of mycothiol S -conjugate amidase, Org Lett, 3, 1543, 10.1021/ol015845+

Nicholas, 2002, Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol- S -conjugate amidase, Bioorg Med Chem Lett, 12, 2487, 10.1016/S0960-894X(02)00385-2

Pick, 2004, Screening of compounds toxicity against human monocytic cell line-THP-1 by flow cytometry, Biol Proced Online, 6, 220, 10.1251/bpo92

Rawat, 2002, Mycothiol-deficient Mycobacterium smegmatis mutants are hypersensitive to alkylating agents, free radicals, and antibiotics, Antimicrob Agents Chemother, 46, 3348, 10.1128/AAC.46.11.3348-3355.2002

Rawat, 2003, Inactivation of mshB , a key gene in the mycothiol biosynthesis pathway in Mycobacterium smegmatis, Microbiology, 149, 1341, 10.1099/mic.0.26084-0

Rawat, 2004, Targeted mutagenesis of the Mycobacterium smegmatis mca gene, encoding a mycothiol-dependent detoxification protein, J Bacteriol, 186, 6050, 10.1128/JB.186.18.6050-6058.2004

Sanford, 1994, Efficient detection and long-term persistence of the carriage of methicillin-resistant Staphylococcus aureus, Clin Infect Dis, 19, 1123, 10.1093/clinids/19.6.1123

Schwalbe, 1987, Emergence of vancomycin resistance in coagulase-negative staphylococci, N Engl J Med, 316, 927, 10.1056/NEJM198704093161507

Tuazon, 1974, Increased rate of carriage of Staphylococcus aureus among narcotic addicts, J Infect Dis, 129, 725, 10.1093/infdis/129.6.725

Tuazon, 1975, Staphylococcus aureus among insulin-injecting diabetic patients. An increased carrier rate, JAMA, 231, 1272, 10.1001/jama.1975.03240240042025

Wagner, 1998, Rational design, synthesis, and X-ray structure of selective noncovalent thrombin inhibitors, J Med Chem, 41, 3664, 10.1021/jm981013e

Weinke, 1992, Association between Staphylococcus aureus nasopharyngeal colonization and septicemia in patients infected with the human immunodeficiency virus, Eur J Clin Microbiol Infect Dis, 11, 985, 10.1007/BF01967787

Wenzel, 1995, The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection, J Hosp Infect, 31, 13, 10.1016/0195-6701(95)90079-9

2002, Tuberculosis , WHO fact sheet, no

Yanisch-Perron, 1985, Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors, Gene, 33, 103, 10.1016/0378-1119(85)90120-9

Yu, 1986, Staphylococcus aureus nasal carriage and infection in patients on hemodialysis. Efficacy of antibiotic prophylaxis, . N Engl J Med, 315, 91, 10.1056/NEJM198607103150204

Thông tin
Thông tin xuất bản

Journal of Medical Microbiology

Tập 55 Số 4

407-415

Thông tin tác giả