Critical Assessment of the Prospects of Quorum-Quenching Therapy for Staphylococcus aureus Infection.
Int J Mol Sci
; 24(4)2023 Feb 16.
Article
em En
| MEDLINE
| ID: mdl-36835436
ABSTRACT
Staphylococcus aureus is an important pathogen that causes a high number of infections and is one of the leading causes of death in hospitalized patients. Widespread antibiotic resistance such as in methicillin-resistant S. aureus (MRSA) has prompted research into potential anti-virulence-targeted approaches. Targeting the S. aureus accessory gene regulator (Agr) quorum-sensing system, a master regulator of virulence, is the most frequently proposed anti-virulence strategy for S. aureus. While much effort has been put into the discovery and screening for Agr inhibitory compounds, in vivo analysis of their efficacy in animal infection models is still rare and reveals various shortcomings and problems. These include (i) an almost exclusive focus on topical skin infection models, (ii) technical problems that leave doubt as to whether observed in vivo effects are due to quorum-quenching, and (iii) the discovery of counterproductive biofilm-increasing effects. Furthermore, potentially because of the latter, invasive S. aureus infection is associated with Agr dysfunctionality. Altogether, the potential of Agr inhibitory drugs is nowadays seen with low enthusiasm given the failure to provide sufficient in vivo evidence for their potential after more than two decades since the initiation of such efforts. However, current Agr inhibition-based probiotic approaches may lead to a new application of Agr inhibition strategies in preventing S. aureus infections by targeting colonization or for otherwise difficult-to-treat skin infections such as atopic dermatitis.
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Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
/
Staphylococcus aureus Resistente à Meticilina
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article