Dataset Information

Deep sequencing whole transcriptome exploration of the ?E regulon in Neisseria meningitidis.

ABSTRACT: Bacteria live in an ever-changing environment and must alter protein expression promptly to adapt to these changes and survive. Specific response genes that are regulated by a subset of alternative ?(70)-like transcription factors have evolved in order to respond to this changing environment. Recently, we have described the existence of a ?(E) regulon including the anti-?-factor MseR in the obligate human bacterial pathogen Neisseria meningitidis. To unravel the complete ?(E) regulon in N. meningitidis, we sequenced total RNA transcriptional content of wild type meningococci and compared it with that of mseR mutant cells (?mseR) in which ?(E) is highly expressed. Eleven coding genes and one non-coding gene were found to be differentially expressed between H44/76 wildtype and H44/76?mseR cells. Five of the 6 genes of the ?(E) operon, msrA/msrB, and the gene encoding a pepSY-associated TM helix family protein showed enhanced transcription, whilst aniA encoding a nitrite reductase and nspA encoding the vaccine candidate Neisserial surface protein A showed decreased transcription. Analysis of differential expression in IGRs showed enhanced transcription of a non-coding RNA molecule, identifying a ?(E) dependent small non-coding RNA. Together this constitutes the first complete exploration of an alternative ?-factor regulon in N. meningitidis. The results direct to a relatively small regulon indicative for a strictly defined response consistent with a relatively stable niche, the human throat, where N. meningitidis resides.

SUBMITTER: Huis in 't Veld RA

PROVIDER: S-EPMC3240639 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Deep sequencing whole transcriptome exploration of the σE regulon in Neisseria meningitidis.

Huis in 't Veld Robert Antonius Gerhardus RA Willemsen Antonius Marcellinus AM van Kampen Antonius Hubertus Cornelis AH Bradley Edward John EJ Baas Frank F Pannekoek Yvonne Y van der Ende Arie A

PloS one 20111215 12

Bacteria live in an ever-changing environment and must alter protein expression promptly to adapt to these changes and survive. Specific response genes that are regulated by a subset of alternative σ(70)-like transcription factors have evolved in order to respond to this changing environment. Recently, we have described the existence of a σ(E) regulon including the anti-σ-factor MseR in the obligate human bacterial pathogen Neisseria meningitidis. To unravel the complete σ(E) regulon in N. menin ...[more]

PMID: 22194974

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Project description:IntroductionThe study presents the analysis of whole genome sequence (WGS) data for Neisseria meningitidis serogroup W isolates recovered in the Czech Republic in 1984-2017 and their comparison with WGS data from other countries.Material and methodsThirty-one Czech N. meningitidis W isolates, 22 from invasive meningococcal disease (IMD) and nine from healthy carriers were analysed. The 33-year study period was divided into three periods: 1984-1999, 2000-2009, and 2010-2017.ResultsMost study isolates from IMD and healthy carriers were assigned to clonal complex cc22 (n = 10) in all study periods. The second leading clonal complex was cc865 (n = 8) presented by IMD (n = 7) and carriage (n = 1) isolates that emerged in the last study period, 2010-2017. The third clonal complex was cc11 (n = 4) including IMD isolates from the first (1984-1999) and third (2010-2017) study periods. The following clonal complex was cc174 (n = 3) presented by IMD isolates from the first two study periods, i.e. 1984-1999 and 2000-2009. One isolate of each cc41/44 and cc1136 originated from healthy carriers from the second study period, 2000-2009. The comparison of WGS data for N. meningitidis W isolates recovered in the Czech Republic in the study period 1984-2017 and for isolates from other countries recovered in the same period showed that clonal complex cc865, ST-3342 is unique to the Czech Republic since 2010. Moreover, the comparison shows that cc11 in the Czech Republic does not comprise novel hypervirulent lineages reported from both European and non-European countries. All 31 study isolates were assigned to Bexsero® Antigen Sequence Types (BAST), and seven of them were of newly described BASTs.ConclusionsWGS analysis contributed considerably to a more detailed molecular characterization of N. meningitidis W isolates recovered in the Czech Republic over a 33-year period and allowed for a spatial and temporal comparison of these characteristics between isolates from the Czech Republic and other countries. The most interesting finding of this study is that eight of 31 Czech isolates of N. meningitidis W belong to clonal complex cc865, which is uncommon for serogroup W. In addition, the WGS data precised the base for the update of the recommendation for vaccination in the Czech Republic.

Project description:During infection Neisseria meningitidis (Nm) encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ?30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating disease cause by this microorganism.

Dataset Information

Deep sequencing whole transcriptome exploration of the ?E regulon in Neisseria meningitidis.

Publications

Deep sequencing whole transcriptome exploration of the σE regulon in Neisseria meningitidis.

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