Productive steps toward an antimicrobial targeting virulence

被引:105
作者
Barczak, Amy K. [3 ]
Hung, Deborah T. [1 ,2 ,4 ,5 ,6 ]
机构
[1] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA
[4] Harvard Univ, Dept Microbiol & Mol Genet, Sch Med, Boston, MA 02114 USA
[5] 7 Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA
[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA
关键词
SMALL-MOLECULE INHIBITOR; RING-FUSED; 2-PYRIDONES; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; BIOFILM FORMATION; PILUS BIOGENESIS; SORTASE; POTENT; IDENTIFICATION; BIOSYNTHESIS;
D O I
10.1016/j.mib.2009.06.012
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学];
摘要
Targeting virulence factors has gained increasing attention as a potential approach to new antibiotics. Small molecule inhibitors of virulence have been shown to change the course of disease in whole organism infection models. Recently, key advances in the field include the identification of novel targets within cell signaling pathways, a new class of anti-virulence compounds that target bacterial defenses against host immunity, and a growing body of in vivo data to support the general approach of anti-virulence therapies. Additionally, there has been a distinct trend toward developing broader spectrum anti-virulence compounds, in particular agents with activity against diverse Gram-negative organisms. Herein we provide an update on the status of the field with a focus on recent advancements.
引用
收藏
页码:490 / 496
页数:7
相关论文
共 49 条
[1]
Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E-coli [J].
Aberg, Veronica ;
Das, Pralay ;
Chorell, Erik ;
Hedenstrom, Mattias ;
Pinkner, Jerome S. ;
Hultgren, Scott J. ;
Almqvist, Fredrik .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (12) :3536-3540
[2]
Pilicides regulate pili expression in E-coli without affecting the functional properties of the pilus rod [J].
Aberg, Veronica ;
Fallman, Erik ;
Axner, Ove ;
Uhlin, Bernt Eric ;
Hultgren, Scott J. ;
Almqvist, Fredrik .
MOLECULAR BIOSYSTEMS, 2007, 3 (03) :214-218
[3]
Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens [J].
Brinster, Sophie ;
Lamberet, Gilles ;
Staels, Bart ;
Trieu-Cuot, Patrick ;
Gruss, Alexandra ;
Poyart, Claire .
NATURE, 2009, 458 (7234) :83-U5
[4]
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein [J].
Bryk, R ;
Lima, CD ;
Erdjument-Bromage, H ;
Tempst, P ;
Nathan, C .
SCIENCE, 2002, 295 (5557) :1073-1077
[5]
Selective killing of nonreplicating mycobacteria [J].
Bryk, Ruslana ;
Gold, Benjamin ;
Venugopal, Aditya ;
Singh, Jasbir ;
Samy, Raghu ;
Pupek, Krzysztof ;
Cao, Hua ;
Popescu, Carmen ;
Gurney, Mark ;
Hotha, Srinivas ;
Cherian, Joseph ;
Rhee, Kyu ;
Ly, Lan ;
Converse, Paul J. ;
Ehrt, Sabine ;
Vandal, Omar ;
Jiang, Xiuju ;
Schneider, Jean ;
Lin, Gang ;
Nathan, Carl .
CELL HOST & MICROBE, 2008, 3 (03) :137-145
[6]
The biology and future prospects of antivirulence therapies [J].
Cegelski, Lynette ;
Marshall, Garland R. ;
Eldridge, Gary R. ;
Hultgren, Scott J. .
NATURE REVIEWS MICROBIOLOGY, 2008, 6 (01) :17-27
[7]
Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A [J].
Chenna, Bala Chandra ;
Shinkre, Bidhan A. ;
King, Jason R. ;
Lucius, Aaron L. ;
Narayana, Sthanam V. L. ;
Velu, Sadanandan E. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (01) :380-385
[8]
Targeting virulence: a new paradigm for antimicrobial therapy [J].
Clatworthy, Anne E. ;
Pierson, Emily ;
Hung, Deborah T. .
NATURE CHEMICAL BIOLOGY, 2007, 3 (09) :541-548
[9]
Targeting virulence traits: potential strategies to combat extraintestinal pathogenic E-coli infections [J].
Dobrindt, Ulrich ;
Hacker, Joerg .
CURRENT OPINION IN MICROBIOLOGY, 2008, 11 (05) :409-413
[10]
N-acyl-3-amino-5H-furanone derivatives as new inhibitors of LuxR-dependent quorum sensing:: Synthesis, biological evaluation and binding mode study [J].
Estephane, Jane ;
Dauvergne, Julien ;
Soulere, Laurent ;
Reverchon, Sylvie ;
Queneau, Yves ;
Doutheau, Alain .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (15) :4321-4324