Antivirulence as a new antibacterial approach for chemotherapy

被引:141
作者
Escaich, Sonia [1 ]
机构
[1] Mutabilis SA, F-93230 Romainville, France
关键词
D O I
10.1016/j.cbpa.2008.06.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bacterial resistance to antibiotics is an issue that has led to the search for new antibacterial approaches. Drugs targeting virulence is an alternative approach to treat infections due to resistant bacteria. There is extensive literature and knowledge in the field of bacterial pathogenesis and genomic determinant of virulence. As therapeutic targets, virulence factors have been primarily addressed in the vaccine field to prevent infection by specific pathogens. Recently novel strategies to identify virulence inhibitors have been numerous and several new compounds were recently reported. This review emphasizes the new virulence inhibitors that have shown a biological activity and have made a proof of concept that disarming bacteria lead to the inhibition of bacterial infection in experimental models in vivo. Moreover, some of these new antivirulence compounds are able to inhibit the virulence of different related pathogenic species, indicating that it is possible to target common virulence mechanisms. The progress reported recently with proof of concept for antivirulence molecules at the preclinical stages should allow the antivirulence concept to become a reality as a new antibacterial approach.
引用
收藏
页码:400 / 408
页数:9
相关论文
共 71 条
[1]   Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2-pyridones -: Targeting virulence of uropathogenic E-coli [J].
Aberg, Veronica ;
Sellstedt, Magnus ;
Hedenstrom, Mattias ;
Pinkner, Jerome S. ;
Hultgren, Scott J. ;
Almqvist, Fredrik .
BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (22) :7563-7581
[2]   Synthesis and inhibitory activity of 8-substituted 2-deoxy-β-KDO against CMP-KDO synthetase [J].
Adachi, Hayamitsu ;
Kondo, Ken-Ichiro ;
Kojima, Fukiko ;
Umezawa, Yoji ;
Ishino, Keiko ;
Hotta, Kunimoto ;
Nishimura, Yoshio .
NATURAL PRODUCT RESEARCH, 2006, 20 (04) :361-370
[3]   Resistance to antibiotics: Are we in the post-antibiotic era? [J].
Alanis, AJ .
ARCHIVES OF MEDICAL RESEARCH, 2005, 36 (06) :697-705
[4]  
ALEKSHUN NM, 2004, DDT, V1, P483
[5]   Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP [J].
Balaban, Naomi ;
Cirioni, Oscar ;
Giacometti, Andrea ;
Ghiselli, Roberto ;
Braunstein, Joel B. ;
Silvestri, Carmela ;
Mocchegiani, Federico ;
Saba, Vittorio ;
Scalise, Giorgio .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (06) :2226-2229
[6]   Staphylococcus aureus virulence factors identified by using a high-throughput Caenorhabditis elegans-killing model [J].
Begun, J ;
Sifri, CD ;
Goldman, S ;
Calderwood, SB ;
Ausubel, FM .
INFECTION AND IMMUNITY, 2005, 73 (02) :872-877
[7]   Large-scale identification of genes required for full virulence of Staphylococcus aureus [J].
Benton, BM ;
Zhang, JP ;
Bond, S ;
Pope, C ;
Christian, T ;
Lee, L ;
Winterberg, KM ;
Schmid, MB ;
Buysse, JM .
JOURNAL OF BACTERIOLOGY, 2004, 186 (24) :8478-8489
[8]   Antibacterial peptides: basic facts and emerging concepts [J].
Boman, HG .
JOURNAL OF INTERNAL MEDICINE, 2003, 254 (03) :197-215
[9]   Regulation of virulence determinants in Staphylococcus aureus:: complexity and applications [J].
Bronner, S ;
Monteil, H ;
Prévost, G .
FEMS MICROBIOLOGY REVIEWS, 2004, 28 (02) :183-200
[10]   Cationic host defense (antimicrobial) peptides [J].
Brown, KL ;
Hancock, REW .
CURRENT OPINION IN IMMUNOLOGY, 2006, 18 (01) :24-30