1887

Abstract

Development of -lactam resistance, production of alginate and modulation of virulence factor expression that alters host immune responses are the hallmarks of chronic infection in cystic fibrosis patients. In this study, we propose that a co-regulatory network exists between these mechanisms. We compared the promoter activities of , , , , , and genes, representing the -lactam antibiotic resistance master regulatory gene, the alginate switch operon, the and quorum-sensing (QS) genes, and the LasA staphylolytic protease, respectively. Four isogenic strains, the prototypic Alg PAO1, Alg PAO, the mucoid Alg PAO (Alg PDO300) and Alg PAO (Alg PDO) were used. We found that in the presence of AmpR regulator and -lactam antibiotic, the extracytoplasmic function sigma factor AlgT/U positively regulated P, whereas AmpR negatively regulated P. On the basis of this finding we suggest the presence of a negative feedback loop to limit expression. In addition, the functional AlgT/U caused a significant decrease in the expression of QS genes, whereas loss of only resulted in increased P and P transcription. The upregulation of the QS system is likely to be responsible for the increased promoter and the LasA protease activities in Alg PAO and Alg PDO. The enhanced expression of virulence factors in the strains correlated with a higher rate of paralysis. Hence, this study shows that the loss of results in increased virulence, and is indicative of the existence of a co-regulatory network between -lactam resistance, alginate production, QS and virulence factor production, with AmpR playing a central role.

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2011-02-01
2019-10-20
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