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Infect Immun ; 87(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31308081

RESUMO

The nosocomial pathogen Pseudomonas aeruginosa regulates its virulence via a complex quorum sensing network, which, besides N-acylhomoserine lactones, includes the alkylquinolone signal molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal [PQS]) and 2-heptyl-4(1H)-quinolone (HHQ). Mycobacteroides abscessus subsp. abscessus, an emerging pathogen, is capable of degrading the PQS and also HHQ. Here, we show that although M. abscessus subsp. abscessus reduced PQS levels in coculture with P. aeruginosa PAO1, this did not suffice for quenching the production of the virulence factors pyocyanin, pyoverdine, and rhamnolipids. However, the levels of these virulence factors were reduced in cocultures of P. aeruginosa PAO1 with recombinant M. abscessus subsp. massiliense overexpressing the PQS dioxygenase gene aqdC of M. abscessus subsp. abscessus, corroborating the potential of AqdC as a quorum quenching enzyme. When added extracellularly to P. aeruginosa cultures, AqdC quenched alkylquinolone and pyocyanin production but induced an increase in elastase levels. When supplementing P. aeruginosa cultures with QsdA, an enzyme from Rhodococcus erythropolis which inactivates N-acylhomoserine lactone signals, rhamnolipid and elastase levels were quenched, but HHQ and pyocyanin synthesis was promoted. Thus, single quorum quenching enzymes, targeting individual circuits within a complex quorum sensing network, may also elicit undesirable regulatory effects. Supernatants of P. aeruginosa cultures grown in the presence of AqdC, QsdA, or both enzymes were less cytotoxic to human epithelial lung cells than supernatants of untreated cultures. Furthermore, the combination of both aqdC and qsdA in P. aeruginosa resulted in a decline of Caenorhabditis elegans mortality under P. aeruginosa exposure.


Assuntos
Hidrolases de Éster Carboxílico/genética , Dioxigenases/genética , Regulação Bacteriana da Expressão Gênica , Mycobacterium abscessus/genética , Pseudomonas aeruginosa/patogenicidade , Percepção de Quorum/genética , Células A549 , Animais , Antibiose/genética , Caenorhabditis elegans/microbiologia , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Dioxigenases/metabolismo , Dioxigenases/farmacologia , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Mycobacterium abscessus/enzimologia , Oligopeptídeos/genética , Oligopeptídeos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Piocianina/genética , Piocianina/metabolismo , Quinolonas/metabolismo , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
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