The biology and future prospects of antivirulence therapies

Abstract

The emergence and increasing prevalence of bacterial strains that are resistant to available antibiotics demand the discovery of new therapeutic approaches. Targeting bacterial virulence is an alternative approach to antimicrobial therapy that offers promising opportunities to inhibit pathogenesis and its consequences without placing immediate life-or-death pressure on the target bacterium. Certain virulence factors have been shown to be potential targets for drug design and therapeutic intervention, whereas new insights are crucial for exploiting others. Targeting virulence represents a new paradigm to empower the clinician to prevent and treat infectious diseases.

Repurposing the antimycotic drug flucytosine for suppression ofPseudomonas aeruginosapathogenicity

“…is a guest editor invited by the Editorial Board. 1 To whom correspondence may be addressed. E-mail: francesco.imperi@uniroma1.it or paolo.visca@uniroma3.it.…”

“…Antivirulence drugs disarm rather than kill pathogens. In principle, they combat bacterial infections without exerting the strong selective pressure for resistance imposed by conventional antibiotics, with no predictable detrimental effect on the host microbiota (1). In the last decade, many antivirulence strategies have been proven effective in animal models of infection (reviewed in ref.…”

Temperature regulation of virulence factors in the pathogen Vibrio coralliilyticus

“…Vc450 exhibits resistance to many common antibiotics (that is, tetracycline, erythromycin and quinolones (Vizcaino et al, 2010)) and to date, phage therapy is the only proposed strategy for mitigation of V. coralliilyticus infections . Elucidating temperature-dependent virulence mechanisms of V. coralliilyticus may assist in the design of antivirulence therapies (Cegelski et al, 2008) for this organism, as well as for other vibrios, which exhibit temperature-related disease outbreaks, including V. cholerae. With the world's oceans changing rapidly (Hoegh-Guldberg and Bruno, 2010), we hypothesize that V. coralliilyticus will become a sustained threat to coral reefs and propose that V. coralliilyticus establishes a model to further elucidate temperature-dependent virulence mechanisms.…”

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

“…For example, bacterial biofilm formation is essential in wastewater treatment and food processing, and, in the context of the microbiome, commensal bacteria play roles in fending off invading pathogens, presumably by relying on quorum-sensing-controlled traits 12,13 . Indeed, anti- and pro-quorum-sensing compounds have been developed and show promise in relevant model systems 14–17 .…”