Pseudomonas aeruginosa quorum-sensing signaling molecule N-3-oxododecanoyl homoserine lactone induces matrix metalloproteinase 9 expression via the AP1 pathway in rat fibroblasts

Abstract

Quorum sensing is a cell-to-cell communication mechanism, which is responsible for regulating a number of bacterial virulence factors and biofilm maturation and therefore plays an important role for establishing wound infection. Quorum-sensing signals may induce inflammation and predispose wounds to infection by Pseudomonas aeruginosa; however, the interaction has not been well investigated. We examined the effects of the P. aeruginosa las quorum-sensing signal, N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL), on matrix metalloproteinase (MMP) 9 expression in Rat-1 fibroblasts. 3OC12-HSL upregulated the expression of the MMP9 gene bearing an activator protein-1 (AP-1) binding site in the promoter region. We further investigated the mechanism underlying this effect. c-Fos gene expression increased rapidly after exposure to 3OC12-HSL, and nuclear translocation of c-Fos protein was observed; both effects were reduced by pretreatment with an AP-1 inhibitor. These results suggest that 3OC12-HSL can alter MMP9 gene expression in fibroblasts via the AP-1 signaling pathway.

Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis

“…The signaling mechanism stimulated by P. aeruginosa secreted factor may be dependent on concentration driven by tumoral P. aeruginosa abundance. P. aeruginosa secretes numerous proteases, lipases, lipopolysaccharides, quinolones, pyocyanin, Cif, or hemolysin-coregulated proteins (16)(17)(18)(19)(20). It also forms multicellular biofilms which are resistant to biotic and abiotic stressors.…”

A influência do quórum sensing na formação do biofilme por Pseudomonas aeruginosa

“…Pode-se dizer que o sistema las é o topo da hierarquia dos sistemas de regulação do quorum sensing, por outro ângulo, o sistema rhl é controlado pelos sistemas las e pqs, porém, parte dos fatores de virulência é ativado por rhl. No geral, a união dos sistemas forma uma cascata de ativação que produz reações que serão desencadeadas surgindo um verdadeiro quorum de células (Lee et al, 2013 A produção de fatores de virulência por Pseudomonas aeruginosa durante infecção aguda, ocorre por meio da ativação dos seus genes-alvos a partir dos autoindutores como: A 3-oxo-C12-HSL estimula a biossíntese da exotoxina A, catalase, pilus, formação do biofilme, motilidade por flagelos ou motilidade twitchcing (Kievit et al, 2001); as moléculas C4-HSL e PQS estimulam ramnolipídeos, piocianina, lecitina A e B. Além desses, a PQS estimula também a produção do cianeto de hidrogênio (Jimenez et al, 2012;Nakagami et al, 2015).…”

Recent Advances in Non-Conventional Antimicrobial Approaches for Chronic Wound Biofilms: Have We Found the ‘Chink in the Armor’?

“…While QS molecules have primarily been implicated in biofilm formation in non-healing wounds, P. aeruginosa autoinducers have also been shown to interfere with host cell signalling [112,113]. For example, the autoinducer 3OC12-HSL induces the expression of MMP-9 in rat fibroblasts and could possibly contribute to wound chronicity.…”