A Novel Phase Variation Mechanism in the Meningococcus Driven by a Ligand-Responsive Repressor and Differential Spacing of Distal Promoter Elements

PLoS Pathogens

Stuart A. Hill¹  Davide Roncarati²  Isabel Delany²  Nathalie Norais³  Francesco Berlanda Scorza³  Eva Pigozzi³  Matteo M. E. Metruccio³  Vincenzo Scarlato³ 

[1] Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois, United States of America;Department of Biology, University of Bologna, Bologna, Italy;Novartis Vaccines and Diagnostics, Siena, Italy

关键词: Neisseria meningitidis;    DNA-binding proteins;    Transcriptional control;    DNA transcription;    Electrophoretic mobility shift assay;    Regulator genes;    DNA footprinting;    Plasmid construction;   

DOI  :  10.1371/journal.ppat.1000710

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Phase variable expression, mediated by high frequency reversible changes in the length of simple sequence repeats, facilitates adaptation of bacterial populations to changing environments and is frequently important in bacterial virulence. Here we elucidate a novel phase variable mechanism for NadA, an adhesin and invasin of Neisseria meningitidis. The NadR repressor protein binds to operators flanking the phase variable tract and contributes to the differential expression levels of phase variant promoters with different numbers of repeats likely due to different spacing between operators. We show that IHF binds between these operators, and may permit looping of the promoter, allowing interaction of NadR at operators located distally or overlapping the promoter. The 4-hydroxyphenylacetic acid, a metabolite of aromatic amino acid catabolism that is secreted in saliva, induces NadA expression by inhibiting the DNA binding activity of the repressor. When induced, only minor differences are evident between NadR-independent transcription levels of promoter phase variants and are likely due to differential RNA polymerase contacts leading to altered promoter activity. Our results suggest that NadA expression is under both stochastic and tight environmental-sensing regulatory control, both mediated by the NadR repressor, and may be induced during colonization of the oropharynx where it plays a major role in the successful adhesion and invasion of the mucosa. Hence, simple sequence repeats in promoter regions may be a strategy used by host-adapted bacterial pathogens to randomly switch between expression states that may nonetheless still be induced by appropriate niche-specific signals.

【 授权许可】

CC BY