1887

Abstract

In the production of multiple virulence factors depends on cell-to-cell communication through the integration of -acylhomoserine lactone (AHL)- and 2-heptyl-3-hydroxy-4(1)-quinolone (PQS)- dependent signalling. Mutation of genes encoding the efflux protein MexI and the porin OpmD from the MexGHI-OpmD pump resulted in the inability to produce -(3-oxododecanoyl)--homoserine lactone (3-oxo-c12-hsl) and pqs and a marked reduction in -butanoyl--homoserine lactone levels. Both pump mutants were impaired in growth and exhibited enhanced rather than reduced antibiotic resistance. Provision of exogenous PQS improved growth and restored AHL and virulence factor production as well as antibiotic susceptibility, indicating that the pump mutants retained their capacity to respond to PQS. RT-PCR analysis indicated that expression of the PQS biosynthetic genes, and , was inhibited when the mutants reached stationary phase, suggesting that the pleiotropic phenotype observed may be due to intracellular accumulation of a toxic PQS precursor. To explore this hypothesis, double (unable to produce anthranilate, the precursor of PQS) and mutants were constructed; the improved growth of the former suggested that the toxic compound is likely to be anthranilate or a metabolite of it. Mutations in and also resulted in the attenuation of virulence in rat and plant infection models. In plants, addition of PQS restored the virulence of and mutants. Collectively, these results demonstrate an essential function for the MexGHI-OpmD pump in facilitating cell-to-cell communication, antibiotic susceptibility and promoting virulence and growth in .

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2005-04-01
2019-09-24
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