Anti-virulence strategies to combat bacteria-mediated disease

Abstract

Antibiotic resistance is one of the greatest challenges of the twenty-first century. However, the increasing understanding of bacterial pathogenesis and intercellular communication has revealed many potential strategies to develop novel drugs to treat bacteria-mediated disease. Interference with bacterial virulence and/or cell-to-cell signalling pathways is an especially compelling approach, as it is thought to apply less selective pressure for the development of bacterial resistance than traditional strategies, which are aimed at killing bacteria or preventing their growth. Here, we discuss the mechanisms of bacterial virulence and present promising anti-virulence strategies and compounds for the future treatment of bacterial infections.

Repurposing the antimycotic drug flucytosine for suppression ofPseudomonas aeruginosapathogenicity

“…In the last decade, many antivirulence strategies have been proven effective in animal models of infection (reviewed in ref. 2), although no antivirulence compound has yet been tested in large-scale clinical trials.…”

Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae

“…Quorum sensing was first discovered in the marine bacterium Vibrio fischeri and was thought to be restricted to only a limited number of species. Later on, similar systems were found to be present in many other bacteria, including a still growing list of bacteria that are pathogenic to plants, animals and humans (Williams et al, 2000;Rasko and Sperandio, 2010). Moreover, signal molecules have been detected in samples retrieved from infected hosts (Singh et al, 2000) and quorum sensing disruption has been reported to result in reduced virulence in different host-pathogen systems (Hentzer et al, 2003;von Bodman et al, 2003;Defoirdt et al, 2008).…”

Quorum quenching quandary: resistance to antivirulence compounds

“…Indeed, it has been decreed that we live in a post-antibiotic era and heralded that anti-quorum sensing (QS)/antivirulence methods hold great promise for treating bacterial infections (Rasko and Sperandio, 2010). One of the most attractive features of this approach is that by interrupting cell signaling, these approaches do not impose harsh or direct selective pressure like antibiotics (Bjarnsholt et al, 2010), so there is less evolutionary pressure to develop resistance to antivirulence compounds (Bjarnsholt et al, 2010;Rasko and Sperandio, 2010).…”

“…Bacteria have been identified that are resistant to all known antibiotics (Defoirdt et al, 2010), and infectious diseases remain the leading cause of death (Rasko and Sperandio, 2010); hence, it is important to develop new antimicrobials. Indeed, it has been decreed that we live in a post-antibiotic era and heralded that anti-quorum sensing (QS)/antivirulence methods hold great promise for treating bacterial infections (Rasko and Sperandio, 2010).…”