Considerations and caveats in anti-virulence drug development.
As antibiotic resistance remains a major public health threat, anti-virulence therapy research is gaining interest. Hundreds of potential anti-virulence compounds have been examined, but very few have made it to clinical trials and none have been approved. This review surveys the current anti-virulence research field with a focus on the highly resistant and deadly ESKAPE pathogens, especially Pseudomonas aeruginosa. We discuss timely considerations and caveats in anti-virulence drug development, including target identification, administration, preclinical development, and metrics for success in clinical trials. Development of a defined pipeline for anti-virulence agents, which differs in important ways from conventional antibiotics, is imperative for the future success of these critically needed drugs.
Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Shriners Hospitals for Children Boston, Boston, MA 02114, USA.
Damien
D
Maura
Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Shriners Hospitals for Children Boston, Boston, MA 02114, USA.
Alicia E
AE
Ballok
Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Shriners Hospitals for Children Boston, Boston, MA 02114, USA. Electronic address: rahme@molbio.mgh.harvard.edu.
Laurence G
LG
Rahme
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity*; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity*; D014774:Virulence / Q000187:drug effects
D000900:Anti-Bacterial Agents