Abstract
DNA uptake sequences are widespread throughout the Neisseria gonorrhoeae genome. These short, conserved sequences facilitate the exchange of endogenous DNA between members of the genus Neisseria. Often the DNA uptake sequences are present as inverted repeats that are able to form hairpin structures. It has been suggested previously that DNA uptake sequence inverted repeats present 3' of genes play a role in rho-independent termination and attenuation. However, there is conflicting experimental evidence to support this role. The aim of this study was to determine the role of DNA uptake sequences in transcriptional termination. Both bioinformatics predictions, conducted using TransTermHP, and experimental evidence, from RNA-seq data, were used to determine which inverted repeat DNA uptake sequences are transcriptional terminators and in which direction. Here we show that DNA uptake sequences in the inverted repeat configuration occur in N. gonorrhoeae both where the DNA uptake sequence precedes the inverted version of the sequence and also, albeit less frequently, in reverse order. Due to their symmetrical configuration, inverted repeat DNA uptake sequences can potentially act as bi-directional terminators, therefore affecting transcription on both DNA strands. This work also provides evidence that gaps in DNA uptake sequence density in the gonococcal genome coincide with areas of DNA that are foreign in origin, such as prophage. This study differentiates for the first time, to our knowledge, between DNA uptake sequences that form intrinsic transcriptional terminators and those that do not, providing characteristic features within the flanking inverted repeat that can be identified.
Highlights
The meningococcal B (MenB) vaccine, Bexsero®, was added to the childhood immunisation programme as part of the routine infant schedule in England from 1 September 2015 and is offered at 2, 4 and 12 months of age
Carbohydrate capsule-based vaccines have been effective at preventing both asymptomatic carriage and invasive meningococcal disease caused by most serogroups of Neisseria meningitidis (Nme)
The carbohydrate capsule of serogroup B strains, which often cause disease in Western nations, are not immunogenic in humans because they mimic neonatal and neural tissue antigens. This has prompted vigorous efforts to develop a new generation of protein-based vaccines that will protect against disease by serogroup B and, ideally, other pathogenic Nme strains
Summary
The meningococcal B (MenB) vaccine, Bexsero®, was added to the childhood immunisation programme as part of the routine infant schedule in England from 1 September 2015 and is offered at 2, 4 and 12 months of age. To understand factors contributing to outbreaks of invasive meningococcal disease (IMD) in men who have sex with men, there is a need to investigate urogenital infections caused by N. meningitidis To this end, whole genome sequence (WGS) data from N. meningitidis urogenital infections were compared with isolates associated with IMD from the same region in the U.K and same time period. Neisseria meningitidis serogroups A, B, C, W, and Y are responsible for the majority of global meningococcal disease In this phase 2b study, we evaluated the immunogenicity of an investigational MenABCWY vaccine, compared with a licenced MenACWY-CRM vaccine, in healthy adolescents aged 1018 years, using two methodologically different serological assays (NCT02140762). While predicted to greatly reduce invasive disease, it remains unknown whether the 4CMenB vaccine will be effective in preventing carriage and transmission, which are essential aspects for long-term vaccine success, and disease eradication
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