Statines et artérites à cellules géantes : approche pharmaco-épidémiologique

Nous proposons une revue de la littérature approfondie sur la pharmacologie des inhibiteurs de l'HMG-CoA réductase et les résultats de nos études sur leur utilisation dans l'artérite à cellules géantes. Nous avons montré que l'exposition aux statines n'est pas associée au risque de survenue d'artérite à cellules géantes dans la population générale. Toutefois, une exposition aux statines jusqu'à 20 mois pourrait favoriser un sevrage plus rapide en corticoïdes. L'utilisation des statines au cours de l'artérite à cellules géantes ne doit pas être définitivement exclu. D'autant plus que nous avons également montré que les patients, diagnostiqués pour une artérite à cellules géantes, les plus âgés ou connus pour avoir des comorbidités cardiovasculaires présentent un risque élevé d'hospitalisation pour évènement cardiovasculaire majeur après la phase initiale de la maladie et doivent être étroitement surveillés en ce sens. Nous montrons qu'il existe un besoin non satisfait en terme de prévention cardiovasculaire dans l'artérite à cellules géantes. Les statines semblent efficaces pour prévenir les événements cardiovasculaires majeurs dans cette population.We propose a comprehensive review on HMG-CoA reductase inhibitors pharmacology and results of our studies on their use in giant cell arteritis. We showed that statins exposure was not associated with giant cell arteritis occurrence in the general population. However, exposure to statins up to 20 months may favor a quicker corticosteroid tapering. Based on those results statin impact on giant cell arteritis course should not be definitively ruled out. We also showed that older giant cell arteritis patients and those suffering from cardiovascular comorbidities present a high risk of cardiovascular hospitalization occurrence after the initial phase of the disease and should be closely monitored to prevent subsequent cardiovascular disease. This proves that there is an unmet need of cardiovascular prevention in giant cell arteritis patients. Statins seems highly efficient to prevent major cardiovascular events in this population

Genome Sequences of Two Tunisian Field Strains of Avian <I>Mycoplasma, M. meleagridis<I> and <I>M. gallinarum<I>

International audienceMycoplasma meleagridis and Mycoplasma gallinarum are bacteria that affect birds, but little is known about the genetic basis of their interaction with chickens and other poultry. Here, we sequenced the genomes of M. meleagridis strain MM_26B8_IPT and M. gallinarum strain Mgn_IPT, both isolated from chickens showing respiratory symptoms, poor growth, reduction in hatchability, and loss of production

Comparative genomics of Mycoplasma feriruminatoris, a fast-growing pathogen of wild Caprinae.

Mycoplasma feriruminatoris is a fast-growing Mycoplasma species isolated from wild Caprinae and first described in 2013. M. feriruminatoris isolates have been associated with arthritis, kerato conjunctivitis, pneumonia and septicemia, but were also recovered from apparently healthy animals. To better understand what defines this species, we performed a genomic survey on 14 strains collected from free-ranging or zoo-housed animals between 1987 and 2017, mostly in Europe. The average chromosome size of the M. feriruminatoris strains was 1,040±0,024 kbp, with 24 % G+C and 852±31 CDS. The core genome and pan-genome of the M. feriruminatoris species contained 628 and 1312 protein families, respectively. The M. feriruminatoris strains displayed a relatively closed pan-genome, with many features and putative virulence factors shared with species from the M. mycoides cluster, including the MIB-MIP Ig cleavage system, a repertoire of DUF285 surface proteins and a complete biosynthetic pathway for galactan. M. feriruminatoris genomes were found to be mostly syntenic, although repertoires of mobile genetic elements, including Mycoplasma Integrative and Conjugative Elements, insertion sequences, and a single plasmid varied. Phylogenetic- and gene content analyses confirmed that M. feriruminatoris was closer to the M. mycoides cluster than to the ruminant species M. yeatsii and M. putrefaciens. Ancestral genome reconstruction showed that the emergence of the M. feriruminatoris species was associated with the gain of 17 gene families, some of which encode defence enzymes and surface proteins, and the loss of 25 others, some of which are involved in sugar transport and metabolism. This comparative study suggests that the M. mycoides cluster could be extended to include M. feriruminatoris. We also find evidence that the specific organization and structure of the DnaA boxes around the oriC of M. feriruminatoris may contribute to drive the remarkable fast growth of this minimal bacterium

Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers

Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined

Mycoplasma mycoides, from "mycoides Small Colony" to "capri". A microevolutionary perspective

<p>Abstract</p> <p>Background</p> <p>The <it>Mycoplasma mycoides </it>cluster consists of five species or subspecies that are ruminant pathogens. One subspecies, <it>Mycoplasma mycoides </it>subspecies <it>mycoides </it>Small Colony (MmmSC), is the causative agent of contagious bovine pleuropneumonia. Its very close relative, <it>Mycoplasma mycoides </it>subsp. <it>capri </it>(Mmc), is a more ubiquitous pathogen in small ruminants causing mastitis, arthritis, keratitis, pneumonia and septicaemia and is also found as saprophyte in the ear canal. To understand the genetics underlying these phenotypic differences, we compared the MmmSC PG1 type strain genome, which was already available, with the genome of an Mmc field strain (95010) that was sequenced in this study. We also compared the 95010 genome with the recently published genome of another Mmc strain (GM12) to evaluate Mmc strain diversity.</p> <p>Results</p> <p>The MmmSC PG1 genome is 1,212 kbp and that of Mmc 95010 is ca. 58 kbp shorter. Most of the sequences present in PG1 but not 95010 are highly repeated Insertion Sequences (three types of IS) and large duplicated DNA fragments. The 95010 genome contains five types of IS, present in fewer copies than in PG1, and two copies of an integrative conjugative element. These mobile genetic elements have played a key role in genome plasticity, leading to inversions of large DNA fragments. Comparison of the two genomes suggested a marked decay of the PG1 genome that seems to be correlated with a greater number of IS. The repertoire of gene families encoding surface proteins is smaller in PG1. Several genes involved in polysaccharide metabolism and protein degradation are also absent from, or degraded in, PG1.</p> <p>Conclusions</p> <p>The genome of MmmSC PG1 is larger than that of Mmc 95010, its very close relative, but has less coding capacity. This is the result of large genetic rearrangements due to mobile elements that have also led to marked gene decay. This is consistent with a non-adaptative genomic complexity theory, allowing duplications or pseudogenes to be maintained in the absence of adaptive selection that would lead to purifying selection and genome streamlining over longer evolutionary times. These findings also suggest that MmmSC only recently adapted to its bovine host.</p

Comparative genomic and proteomic analyses of two Mycoplasma agalactiae strains: clues to the macro- and micro-events that are shaping mycoplasma diversity

Background: While the genomic era is accumulating a tremendous amount of data, the question of how genomics can describe a bacterial species remains to be fully addressed. The recent sequencing of the genome of the Mycoplasma agalactiae type strain has challenged our general view on mycoplasmas by suggesting that these simple bacteria are able to exchange significant amount of genetic material via horizontal gene transfer. Yet, events that are shaping mycoplasma genomes and that are underlining diversity within this species have to be fully evaluated. For this purpose, we compared two strains that are representative of the genetic spectrum encountered in this species: the type strain PG2 which genome is already available and a field strain, 5632, which was fully sequenced and annotated in this study. Results: The two genomes differ by ca. 130 kbp with that of 5632 being the largest (1006 kbp). The make up of this additional genetic material mainly corresponds (i) to mobile genetic elements and (ii) to expanded repertoire of gene families that encode putative surface proteins and display features of highly-variable systems. More specifically, three entire copies of a previously described integrative conjugative element are found in 5632 that accounts for ca. 80 kbp. Other mobile genetic elements, found in 5632 but not in PG2, are the more classical insertion sequences which are related to those found in two other ruminant pathogens, M. bovis and M. mycoides subsp. mycoides SC. In 5632, repertoires of gene families encoding surface proteins are larger due to gene duplication. Comparative proteomic analyses of the two strains indicate that the additional coding capacity of 5632 affects the overall architecture of the surface and suggests the occurrence of new phase variable systems based on single nucleotide polymorphisms. Conclusion: Overall, comparative analyses of two M. agalactiae strains revealed a very dynamic genome which structure has been shaped by gene flow among ruminant mycoplasmas and expansion-reduction of gene repertoires encoding surface proteins, the expression of which is driven by localized genetic micro-events

Being Pathogenic, Plastic, and Sexual while Living with a Nearly Minimal Bacterial Genome

Mycoplasmas are commonly described as the simplest self-replicating organisms, whose evolution was mainly characterized by genome downsizing with a proposed evolutionary scenario similar to that of obligate intracellular bacteria such as insect endosymbionts. Thus far, analysis of mycoplasma genomes indicates a low level of horizontal gene transfer (HGT) implying that DNA acquisition is strongly limited in these minimal bacteria. In this study, the genome of the ruminant pathogen Mycoplasma agalactiae was sequenced. Comparative genomic data and phylogenetic tree reconstruction revealed that ∼18% of its small genome (877,438 bp) has undergone HGT with the phylogenetically distinct mycoides cluster, which is composed of significant ruminant pathogens. HGT involves genes often found as clusters, several of which encode lipoproteins that usually play an important role in mycoplasma–host interaction. A decayed form of a conjugative element also described in a member of the mycoides cluster was found in the M. agalactiae genome, suggesting that HGT may have occurred by mobilizing a related genetic element. The possibility of HGT events among other mycoplasmas was evaluated with the available sequenced genomes. Our data indicate marginal levels of HGT among Mycoplasma species except for those described above and, to a lesser extent, for those observed in between the two bird pathogens, M. gallisepticum and M. synoviae. This first description of large-scale HGT among mycoplasmas sharing the same ecological niche challenges the generally accepted evolutionary scenario in which gene loss is the main driving force of mycoplasma evolution. The latter clearly differs from that of other bacteria with small genomes, particularly obligate intracellular bacteria that are isolated within host cells. Consequently, mycoplasmas are not only able to subvert complex hosts but presumably have retained sexual competence, a trait that may prevent them from genome stasis and contribute to adaptation to new hosts

A novel substitution matrix fitted to the compositional bias in Mollicutes improves the prediction of homologous relationships

<p>Abstract</p> <p>Background</p> <p>Substitution matrices are key parameters for the alignment of two protein sequences, and consequently for most comparative genomics studies. The composition of biological sequences can vary importantly between species and groups of species, and classical matrices such as those in the BLOSUM series fail to accurately estimate alignment scores and statistical significance with sequences sharing marked compositional biases.</p> <p>Results</p> <p>We present a general and simple methodology to build matrices that are especially fitted to the compositional bias of proteins. Our approach is inspired from the one used to build the BLOSUM matrices and is based on learning substitution and amino acid frequencies on real sequences with the corresponding compositional bias. We applied it to the large scale comparison of Mollicute AT-rich genomes. The new matrix, MOLLI60, was used to predict pairwise orthology relationships, as well as homolog families among 24 Mollicute genomes. We show that this new matrix enables to better discriminate between true and false orthologs and improves the clustering of homologous proteins, with respect to the use of the classical matrix BLOSUM62.</p> <p>Conclusions</p> <p>We show in this paper that well-fitted matrices can improve the predictions of orthologous and homologous relationships among proteins with a similar compositional bias. With the ever-increasing number of sequenced genomes, our approach could prove valuable in numerous comparative studies focusing on atypical genomes.</p