Abstract
ABSTRACT Whooping cough, or pertussis, is resurgent in numerous countries worldwide. This has renewed interest in Bordetella pertussis biology and vaccinology. The in vitro growth of B. pertussis has been a source of difficulty, both for the study of the organism and the production of pertussis vaccines. It is inhibited by fatty acids and other hydrophobic molecules. The AcrAB efflux system is present in many different bacteria and in combination with an outer membrane factor exports acriflavine and other small hydrophobic molecules from the cell. Here, we identify that the speciation of B. pertussis has selected for an Acr system that is naturally mutated and displays reduced activity compared to B. bronchiseptica, in which the system appears intact. Replacement of the B. pertussis locus with that of B. bronchiseptica conferred higher levels of resistance to growth inhibition by acriflavine and fatty acids. In addition, we identified that the transcription of the locus is repressed by a LysR-type transcriptional regulator. Palmitate de-represses the expression of the acr locus, dependent on the LysR regulator, strongly suggesting that it is a transcriptional repressor that is regulated by palmitate. It is intriguing that the speciation of B. pertussis has selected for a reduction in activity of the Acr efflux system that typically is regarded as protective to bacteria.
Highlights
IntroductionThe genus Bordetella consists of nine characterized species (recently other novel species have been reported), including those that cause respiratory infections
The genus Bordetella consists of nine characterized species, including those that cause respiratory infections
B. pertussis has suffered two deletions, in acrA and cusC that results in a reduction in activity of B. pertussis AcrABC leading to an increase in sensitivity to ampicillin, acriflavine and fatty acids
Summary
The genus Bordetella consists of nine characterized species (recently other novel species have been reported), including those that cause respiratory infections. Pertussis is considered resurgent in many parts of the world, despite high levels of vaccination. In the commonly used laboratory media B. pertussis releases fatty acids, palmitic acid, into the culture supernatant to concentrations that inhibit growth [11]. This contributes to a poor yield from in vitro B. pertussis cultures and to issues with reproducibility of the quality of the biomass produced, creating major problems for vaccine manufacturers.
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