The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus

Group B Streptococcus (GBS), a common commensal of the female genital tract, is the leading cause of invasive infections in neonates. Expression of major GBS virulence factors, such as the hemolysin operon cyl, is regulated directly at the transcriptional level by the CovSR two-component system. Using a random genetic approach, we identified a multi-spanning transmembrane protein, Abx1, essential for the production of the GBS hemolysin. Despite its similarity to eukaryotic CaaX proteases, the Abx1 function is not involved in a post-translational modification of the GBS hemolysin. Instead, we demonstrate that Abx1 regulates transcription of several virulence genes, including those comprising the hemolysin operon, by a CovSR-dependent mechanism. By combining genetic analyses, transcriptome profiling, and site-directed mutagenesis, we showed that Abx1 is a regulator of the histidine kinase CovS. Overexpression of Abx1 is sufficient to activate virulence gene expression through CovS, overcoming the need for an additional signal. Conversely, the absence of Abx1 has the opposite effect on virulence gene expression consistent with CovS locked in a kinase-competent state. Using a bacterial two-hybrid system, direct interaction between Abx1 and CovS was mapped specifically to CovS domains involved in signal processing. We demonstrate that the CovSR two-component system is the core of a signaling pathway integrating the regulation of CovS by Abx1 in addition to the regulation of CovR by the serine/threonine kinase Stk1. In conclusion, our study reports a regulatory function for Abx1, a member of a large protein family with a characteristic Abi-domain, which forms a signaling complex with the histidine kinase CovS in GBS

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. \ua9 2014 Macmillan Publishers Limited. All rights reserved

“ModelOmics: Approaches in environmental genomics for modeling the metabolism of microbial communities and studying its evolution”

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Réseaux de régulation et éléments intégratifs et conjugatifs de la famille TnGBS dans l'adaptation de Streptococcus agalactiae

S. agalactiae (GBS) was initially described as responsible for bovine mastitis, but is now recognized as a leading cause of infections in neonates causing pneumonia, septicemia, and meningitidis. However, this bacterium is primarily a commensal of the human digestive and genitourinary tracts. To colonize and to adapt to this broad range of environments, GBS utilizes transcriptional regulators. Using transcriptomic approaches, we have characterized some of these regulatory systems. In particular, we have demonstrated that the D-alanylation of the LTA is under the control of a dual feedback loop involving the two TCS DltRS and CiaRH. This dual regulation ensure a fine-turning of the expression of the dlt operon expression and consequently of the net charge of the bacterial cell surface. We have also shown that the loci encoding the virulence factors Srr and PI-2a are regulated by two transcription factors of RofA-like family, and also regulated by CovRS regulatory system belonging to the core genome. The EGMs are the major contributor of genome evolution by lateral gene transfer. We have characterized a new family of ICEs ,the TnGBS, corresponding to the first family of ICEs whose excision/integration is mediated by a DDE transposase. Another characteristic of this family is their insertion specificity upstream promoters sequences. The characterization and the comparative analysis of TnGBS related elements led to define the proteins implicated in the different steps of the conjugation process. The TnGBS related elements can be classified in subgroups sharing the tranposase but associated with two different conjugation machineriesS. agalactiae (SGB), première cause d'infections néonatales, est aussi associé à des infections chez l'animal. Or, c'est avant tout une bactérie commensale du tube digestif chez l'homme. Son génome est riche en gènes codant pour des systèmes de régulation qui participent à l'adaptation de la bactérie à différents environnements. En partant de l'analyse de données de transcriptomes, j'ai caractérisé la réponse transcriptionnelle associée à plusieurs de ces systèmes de régulation. J'ai pu mettre en évidence que le processus de D-alanylation, responsable de l'ajustement de la charge nette à la surface de la bactérie, est contrôlé par deux boucles de rétrorégulation faisant intervenir deux TCS CiaRH et DltRS. J'ai également étudié la régulation de l'expression de deux facteurs de virulence, la protéine Srr et le pilus PI-2a, qui fait intervenir une régulation croisée de régulateurs de la famille RofA-like et un contrôle indirect par le régulateur CovRS appartenant au core génome. Les EGMs jouent un rôle majeur dans l'évolution des génomes par transfert horizontal. Chez SGB, une nouvelle famille d'ICEs, les TnGBS, est impliquée dans des phénomènes de transfert de type Hfr. Nous avons montré qu'ils constituent la première famille d'ICE codant pour une transposase à motif DDE. Ils possèdent aussi une spécificité d'insertion originale au niveau des régions promotrices. L'analyse comparative des séquences de ces ICE a permis de prédire les protéines impliquées dans les différentes phases du processus de conjugaison. Les TnGBS forment deux sous-familles qui associent une même transposase avec deux modules de conjugaison , de réplication distinct

ModelOmics : approches en génomique environnementale pour la modélisation du métabolisme de communautés microbiennes et l’étude de son évolution dans les écosystèmes

International audienceLe projet proposé permettra de comprendre les déterminants de ces communautés microbiennes complexes (symbioses/holobiontes), par des approches de reconstruction de réseaux métaboliques à l’échelle de chacun des organismes mais également à l’échelle des communautés, avec un focus dans un premier temps aux communautés des écosystèmes marins.Ce projet sera réalisé selon 3 axes complémentaires1- Réseaux métaboliques à l’échelle des génomes et des pangénomes.Cette première partie aura pour but la reconstruction des réseaux métaboliques à l’échelle des génomes de microorganismes mais également des pangénomes d’espèces pour lesquelles nous disposons de plusieurs dizaines, voire milliers de génomes. Accéder au métabolisme microbien à partir de l’information génomique permet ainsi de mieux cerner le rôle des microorganismes qui sont des acteurs majeurs des cycles biogéochimiques et du recyclage (C,N, S, H), notamment dans les écosystèmes marins et océaniques de surface et profonds2- Diversité et ´évolution des voies métaboliques à l'échelle de l’arbre du vivantCette seconde partie aura pour but d’étudier la diversité et l’évolution de voies métaboliques à l’échelle de l’arbre du vivant. Nous pourrons ainsi distinguer les convergences évolutives des évolutions parallèles, et le rô!e des transferts horizontaux, dans l’évolution de ces voies métaboliques.3- Voies métaboliques à l’échelle des écosystèmesCette troisième partie aura pour but d’identifier et de quantifier des voies métaboliquesd’importance pour des écosystèmes et, également, de déterminer si les espèces impliquéesdans ces voies métaboliques d’intérêt sont toujours les mêmes au sein d’écosystèmes similaires (provenant de différentes régions géographiques

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by com- parative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates

The expanding Asgard archaea and their elusive relationships with Eukarya

Abstract The discovery of Asgard archaea and the exploration of their diversity over the last 6 years have deeply impacted the scientific community working on eukaryogenesis, rejuvenating an intense debate on the topology of the universal tree of life (uTol). Here, we discuss how this debate is impacted by two recent publications that expand the number of Asgard lineages and eukaryotic signature proteins (ESPs). We discuss some of the main difficulties that can impair the phylogenetic reconstructions of the uTol and suggest that the debate about its topology is not settled. We notably hypothesize the existence of horizontal gene transfers between ancestral Asgards and proto‐eukaryotes that could result in the observed abnormal behaviors of some Asgard ESPs and universal marker proteins. This hypothesis is relevant regardless of the scenario considered regarding eukaryogenesis. It implies that the Asgards were already diversified before the last eukaryotic common ancestor and shared the same biotopes with proto‐eukaryotes. We suggest that some Asgards might be still living in symbiosis today with modern Eukarya

Engineered bacterium fuels evolution debate

International audienceComment on the intense debate over the origin of eukaryotes is being fuelled by the lipids in the cell membrane of an engineered bacterium (see Nature 569, 322–324; 2019)