Novel agents to inhibit microbial virulence and pathogenicity.
BACKGROUND
The rising levels of antibiotic resistance in pathogenic microorganisms create an urgent need for new antimicrobial agents that are not affected by resistance mechanisms already present in the bacterial population. Targeting virulence is one of the alternative approaches to find new molecules to treat infections due to resistant bacteria. Novel strategies to identify these new antimicrobial agents have been reported.


METHODS
A variety of virulence factors are now the target for inhibition mainly in the antibacterial field. This review focuses exclusively on the new virulence inhibitors published in patents (worldwide collection of patents filed) or in the literature since 2006.


RESULTS
New efficacy in vitro assays have been developed allowing screening of large numbers of molecules. These inhibitors are mainly antibacterial molecules, a few natural products, peptides and antibodies. A growing number of these published studies provide results showing a proof of concept with antivirulence compounds that were able to prevent or treat an infection in vivo. Moreover, some new antivirulence agents could inhibit virulence mechanisms that are common to different related pathogenic species, extending the potential spectrum of antivirulence compounds.


CONCLUSIONS
The progress reported recently for antivirulence molecules at the preclinical stages should allow new classes of molecules to enter into development as new antimicrobial agents with new mechanisms of action.
Escaich
Sonia
S
Fabpharma c/oTioga venture, 336 Rue Saint Honoré, 75012 Paris, France. sonia.escaich@fabpharma.com
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006801:Humans; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D037521:Virulence Factors