A evolução do aumento da expectativa de vida registrada nas últimas décadas foi uma conquista significativa para a sociedade e trouxe novos desafios em diversas áreas do conhecimento humano. Dentre os impactos do aumento da longevidade, destaca-se sua influência no equilíbrio técnico dos planos previdenciários. Nas entidades de previdência complementar, a identificação oportuna de possíveis desvios da premissa da mortalidade à realidade subjacente visa garantir a solvência e a manutenção dos benefícios de longo prazo. Assim, o presente estudo tem por objetivo estimar os fatores de improvement (fator redutor de mortalidade) para a população coberta por planos privados de aposentadoria, com base no método Lee-Carter e na abordagem CMI (Continuous Mortality Investigation), bem como analisar o impacto da incorporação da estimativa do aumento da expectativa de vida no fluxo de caixa atuarial em uma carteira de benefício definido. Em virtude da carência de informações históricas de tábuas de mortalidade para o Brasil, fez-se uso da técnica de pareamento (propensity score), o qual consiste na identificação do país que mais se assemelha ao Brasil no que se refere às variáveis socioeconômicas relevantes para prever a evolução da expectativa de vida. Essa técnica foi aplicada para uma amostra de 21 países da OCDE. As variáveis socioeconômicas consideradas no estudo foram: Fertilidade, PIB per capita, Crescimento anual do PIB, Saúde, Desemprego, Gini, Analfabetismo e Escolaridade. Diante dos testes efetuados, Portugal foi escolhido para servir de base para as projeções da mortalidade e obtenção dos fatores de improvement, em decorrência da técnica de pareamento e do teste de aderência realizado. Comparando-se as médias dos fluxos de caixa da AT-2000 com e sem improvement e levando-se em consideração os cenários de taxas de juros de 3%, 4%, 5% e 6% ao ano, observou-se que, não considerar o improvement, gera uma elevação do fluxo atuarial entre 7,15% a 10,51% para a carteira simulada. A projeção pelo método CMI forneceu resultado semelhante, sendo que o impacto variou entre 7,05% a 10,32%. Embora os métodos de improvement sejam bem diferentes, é importante destacar que os resultados foram bem semelhantes. Um ponto que merece preocupação é a questão da taxa de juros, pois com a tendência de queda, no longo prazo, maior será a sensibilidade do impacto da projeção do risco de longevidade. Adicionalmente, compararam-se os resultados obtidos com a Tábua Geracional RP-2000 e a Tábua SUSEP BR-EMS. Assim, os resultados anteriores mostram que não considerar a tendência de aumento da expectativa de vida na constituição das provisões técnicas pode expor as entidades de previdência a riscos pouco suportáveis no longo prazo. / The evolution of increased life expectancy recorded in recent decades has been a significant achievement for the society and brought new challenges in various areas of human knowledge. Among those, living longer has impacted the technical balance of the pension plans. In the private pension entities, the timely identification of possible deviations from the assumption of mortality to the underlying reality is to ensure the solvency and the maintenance of long-term benefits. Thus, based on Lee-Carter method and approach CMI (Continuous Mortality Investigation Bureau), this study aims to estimate the factors of improvement (reduction factor of mortality) for the population covered by pension plans as well as analyze the impact of incorporating an estimated longer life expectancy on actuarial cash flow into a portfolio of defined benefits. Due to a lack of historical information about mortality tables of Brazil, the matching technique (propensity score) was used to identify the country which is the most similar to Brazil concerning relevant socioeconomic variables, in order to predict the evolution of life expectancy. This technique was applied on 21 OECD sample countries. Socioeconomic variables considered were: Fertility, GDP per capita, annual growth of GDP, Health, Unemployment, Gini, Illiteracy and Schooling. According to test results, Portugal was chosen as the basis for projections of mortality and acquisition of factors of improvement, due to the matching technique and the adherence test performed. Comparing the averages of the cash flows of the AT-2000 with and without improvement and taking into account the scenarios of interest rates of 3%, 4%, 5% and 6% a year, it was observed that not considering the improvement generates an increased actuarial flow between 7.15% and 10.51% for the simulated portfolio. The CMI method provided similar projection, and the impact varied from 7.05% to 10.32%. Even though the methods of improvement are quite different, it is important to emphasize that the results were much the same. One point that deserves concern is the issue of interest rate since, due to the declining trend in the long run more sensitive will be the impact of the projection of longevity risk. Additionally, those results were compared with the table Generational RP-2000 and BRTable SUSEP EMS. Thus, previous results show that not considering the trend of increasing life expectancy in the establishment of technical provisions can expose the private pension entities to a little bearable risk in the long term.

A evolução do aumento da expectativa de vida registrada nas últimas décadas foi uma conquista significativa para a sociedade e trouxe novos desafios em diversas áreas do conhecimento humano. Dentre os impactos do aumento da longevidade, destaca-se sua influência no equilíbrio técnico dos planos previdenciários. Nas entidades de previdência complementar, a identificação oportuna de possíveis desvios da premissa da mortalidade à realidade subjacente visa garantir a solvência e a manutenção dos benefícios de longo prazo. Assim, o presente estudo tem por objetivo estimar os fatores de improvement (fator redutor de mortalidade) para a população coberta por planos privados de aposentadoria, com base no método Lee-Carter e na abordagem CMI (Continuous Mortality Investigation), bem como analisar o impacto da incorporação da estimativa do aumento da expectativa de vida no fluxo de caixa atuarial em uma carteira de benefício definido. Em virtude da carência de informações históricas de tábuas de mortalidade para o Brasil, fez-se uso da técnica de pareamento (propensity score), o qual consiste na identificação do país que mais se assemelha ao Brasil no que se refere às variáveis socioeconômicas relevantes para prever a evolução da expectativa de vida. Essa técnica foi aplicada para uma amostra de 21 países da OCDE. As variáveis socioeconômicas consideradas no estudo foram: Fertilidade, PIB per capita, Crescimento anual do PIB, Saúde, Desemprego, Gini, Analfabetismo e Escolaridade. Diante dos testes efetuados, Portugal foi escolhido para servir de base para as projeções da mortalidade e obtenção dos fatores de improvement, em decorrência da técnica de pareamento e do teste de aderência realizado. Comparando-se as médias dos fluxos de caixa da AT-2000 com e sem improvement e levando-se em consideração os cenários de taxas de juros de 3%, 4%, 5% e 6% ao ano, observou-se que, não considerar o improvement, gera uma elevação do fluxo atuarial entre 7,15% a 10,51% para a carteira simulada. A projeção pelo método CMI forneceu resultado semelhante, sendo que o impacto variou entre 7,05% a 10,32%. Embora os métodos de improvement sejam bem diferentes, é importante destacar que os resultados foram bem semelhantes. Um ponto que merece preocupação é a questão da taxa de juros, pois com a tendência de queda, no longo prazo, maior será a sensibilidade do impacto da projeção do risco de longevidade. Adicionalmente, compararam-se os resultados obtidos com a Tábua Geracional RP-2000 e a Tábua SUSEP BR-EMS. Assim, os resultados anteriores mostram que não considerar a tendência de aumento da expectativa de vida na constituição das provisões técnicas pode expor as entidades de previdência a riscos pouco suportáveis no longo prazo. / The evolution of increased life expectancy recorded in recent decades has been a significant achievement for the society and brought new challenges in various areas of human knowledge. Among those, living longer has impacted the technical balance of the pension plans. In the private pension entities, the timely identification of possible deviations from the assumption of mortality to the underlying reality is to ensure the solvency and the maintenance of long-term benefits. Thus, based on Lee-Carter method and approach CMI (Continuous Mortality Investigation Bureau), this study aims to estimate the factors of improvement (reduction factor of mortality) for the population covered by pension plans as well as analyze the impact of incorporating an estimated longer life expectancy on actuarial cash flow into a portfolio of defined benefits. Due to a lack of historical information about mortality tables of Brazil, the matching technique (propensity score) was used to identify the country which is the most similar to Brazil concerning relevant socioeconomic variables, in order to predict the evolution of life expectancy. This technique was applied on 21 OECD sample countries. Socioeconomic variables considered were: Fertility, GDP per capita, annual growth of GDP, Health, Unemployment, Gini, Illiteracy and Schooling. According to test results, Portugal was chosen as the basis for projections of mortality and acquisition of factors of improvement, due to the matching technique and the adherence test performed. Comparing the averages of the cash flows of the AT-2000 with and without improvement and taking into account the scenarios of interest rates of 3%, 4%, 5% and 6% a year, it was observed that not considering the improvement generates an increased actuarial flow between 7.15% and 10.51% for the simulated portfolio. The CMI method provided similar projection, and the impact varied from 7.05% to 10.32%. Even though the methods of improvement are quite different, it is important to emphasize that the results were much the same. One point that deserves concern is the issue of interest rate since, due to the declining trend in the long run more sensitive will be the impact of the projection of longevity risk. Additionally, those results were compared with the table Generational RP-2000 and BRTable SUSEP EMS. Thus, previous results show that not considering the trend of increasing life expectancy in the establishment of technical provisions can expose the private pension entities to a little bearable risk in the long term.

Les concentrations sous-inhibitrices (sub-CMI) de antibiotiques jouent un rôle important dans la sélection et le développement des résistances. Contrairement à Escherichia coli, Vibrio cholerae induit la réponse SOS en présence de sub-CMI d'aminosides. SOS est également impliquée dans la plasticité du génome et dans l'acquisition de la résistance aux antibiotiques. Afin de sélectionner des mutants de V. cholerae qui n'induisent pas SOS en présence de sub-CMI d'aminosides, nous avons développé un crible génétique pour l'isolement de mutants dans lesquels l'induction de la réponse SOS est perdue. L'un de ces mutants est inactivé pour le gène radD, qui code pour une hélicase ADN/ARN putative. RadD est impliquée dans la résolution de cassures d'ADN double brin (DSB) provoquées par des sub-CMI de tobramycine. Nous avons montré que les R-loops sont à l'origine des DSB formés en absence de radD en tobramycine. Nous suggérons que les lésions de l'ADN formées lors du traitement par aminoglycosides soient réparées par la formation d'intermédiaires ssDNA induisant SOS. L’ARNPol bloquée sur ces lésions peut faciliter la formation de R-loops qui, si elles ne sont pas réparées, peuvent entraîner la formation de DSB et l'instabilité du génome. RadD pourrait jouer un rôle dans la résolution des R-loops. Ces résultats ont mis en évidence le fait que les sub-CMI de tobramycine conduisent à DSB, dues en partie aux R-loops. La tobramycine est un aminoside qui cible le ribosome. La formation de DSB par un tel antibiotique peut être surprenante car la formation de lésions de l'ADN par un antibiotique qui cible la traduction n'est pas attendue. Afin de comprendre les voies impliquées dans la réponse à de sub-CMI de tobramycine, nous avons adopté une approche Tn-seq à haut débit pour déterminer quels gènes sont importants pour maintenir l'intégrité de la cellule en présence d'antibiotiques à faibles doses. / Sub-inhibitory concentrations (sub-MIC) of antibiotics play an important role in selection and development of resistances. Unlike Escherichia coli, Vibrio cholerae induces its SOS response in presence of sub-MIC aminoglycosides. SOS is also involved in genome plasticity and in the acquisition of resistance to antibiotics. In order to select for V. cholerae mutants that do not induce low aminoglycoside-mediated SOS induction, we developed a genetic screen for the isolation of mutants in which induction of the SOS response by sub-MICs of aminoglycosides is lost. One of these mutants is inactivated for the radD gene, which encodes a putative DNA/RNA helicase. RadD is involved in the resolution of double strand DNA breaks caused by treatment with sub-MIC of tobramycine. We demonstrate that R-loops are at the origin of DSBs formed in the absence of radD in tobramycine.We propose that DNA lesions formed upon aminoglycoside treatment are repaired through the formation of ssDNA intermediates, inducing SOS. RNAP could stalls on these lesions and forms R-loops, that, if not repaired, can lead to the formation of DSB and genome instability. RadD could play a role in the resolution of R-loops. These results highlighted the fact that sub-MIC of tobramycine leads to DNA double strand breaks, at least partly through R-loop formation. Tobramycin is an aminoglycoside that targets the ribosome. The formation of DSBs by such an antibiotic can be surprising as DNA damage formation by an antibiotic that targets translation is not expected. In order to understand the pathways involved in the response to low doses of tobramycin we adopted a high throughput Tn-seq approach to determine which genes are important in maintaining the integrity of the cell in the presence of antibiotics at low doses.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

abstract: Although young males are still the primary perpetrators of juvenile crime, girls are increasingly coming into contact with the criminal justice system. While girls may have different pathways to crime and risks for recidivism than boys, their risk to reoffend is typically assessed using a gender-neutral tool that is based on social learning theory: a theory originally developed and tested on males. With the appropriateness of using gender-neutral tools to assess female criminality coming into question, a number of researchers have searched for a resolution. To date, mixed findings on the predictive validity of risk assessment tools have not provided any definitive answers. To help assess the predictive validity of the Youth Level of Service Inventory, separate meta-analyses were conducted for male and female juvenile offenders using previous studies. The mean effect sizes were compared in order to determine whether the predictive validity is similar for both males and females. With the exception of violent recidivism, results indicate that the YLS/CMI works equally well for male and female offenders. The implications of these findings for theory, research, and correctional policy are discussed. / Dissertation/Thesis / Masters Thesis Criminology and Criminal Justice 2016

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-07-22T12:40:38Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação - Nataliane Marques de Vasconcelos.pdf: 1186432 bytes, checksum: 7aaaefe15061c83ecc86656db0d731f1 (MD5) / Made available in DSpace on 2016-07-22T12:40:38Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação - Nataliane Marques de Vasconcelos.pdf: 1186432 bytes, checksum: 7aaaefe15061c83ecc86656db0d731f1 (MD5) Previous issue date: 2016-02-26 / CNPq / A resistência microbiológica aos antibióticos constitui uma série problemas de saúde pública por dificultar o tratamento das infecções. As actinobactérias são fontes importantes para a descobertas de novas moléculas com atividades biológicas. A este grupo, o gênero Streptomyces possuem dentre outros, dois grupos de enzimas multimoduladoras conhecidas como policetídeo sintase (PKS) e peptídeo sintase não ribossomal (NRPS), genes relacionados com a produção de metabólitos secundários. O presente trabalho teve como objetivo investigar o potencial in vitro de metabólitos bioativos produzidos por Actinobactérias isoladas do bioma Caatinga com atividade contra diferentes isolados clínicos de Candida spp. Após ensaio primário das 45 actinobactérias apenas a linhagem PR- 32 apresentou atividade contra Candida spp, com halos de até 20 mm no meio ISP2. Posteriormente, essa linhagem foi cultivada em seis diferentes meios de cultura sendo observada melhor produção do metabólito secundário no meio 400 em 48 horas (h) de fermentação. A determinação da concentração mínima inibitória (CMI) foi determinada a partir do extrato etanólico da biomassa de PR- 32 em pH 7.0 e foi evidenciada uma CMI entre 31,25 μg/mL a 3,9 μg/mL para as leveduras testadas. A cinética de morte reforçou o resultado da CMI e mostrou que no período de 4-8 h o extrato inibiu as cepas de Candida spp. A caracterização da actinobactéria foi identificada por metodologias clássicas e pela pesquisa do gene 16S rRNA como Streptomyces sp. PR- 32. Os resultados desta caracterização sugerem uma possível espécie nova, contudo outras análises ainda precisam ser realizadas. Foi evidenciada a presença do gene nrps com aproximadamente 750 kb. Diante destes resultados podemos concluir que Streptomyces sp. PR- 32 é um isolado promissor para produção de compostos antifúngicos, sendo possível sugerir que a atividade biológica deste metabólito secundário é regulado por peptídeo sintase não ribossomal (NRPS). / The microbial resistance to antibiotics is a series of public health problems for hindering the treatment of infections. The actinomycetes are important sources for new molecules with biological activities discovered. In this group, the genus Streptomyces have among others, multimoduladoras two groups of enzymes known as polyketide synthase (PKS) and non-ribosomal peptide synthase (NRPS), genes involved in production of secondary metabolites. This study aimed to investigate the potential in vitro bioactive metabolites produced by isolated Actinobacteria biome Caatinga with activity against different clinical isolates of Candida spp. After screening of actinomycetes in 45 primary test only the PR- 32 strain showed activity against Candida spp, with halos of up to 20 mm in the middle ISP2. Subsequently, this strain was grown in six different culture media is best seen in secondary metabolite production means 400 at 48 h of fermentation. The determination of the minimum inhibitory concentration (MIC) was determined from the ethanolic extract of the biomass of PR- 32 at pH 7.0 and one MIC was observed between 31.25 mg / mL 3.9 mg / mL for yeast tested. The kinetics of death reinforced the result of CMI and showed that in the 4-8 hour period the extract inhibited the strains of Candida spp. The characterization of actinobacteria was identified by classical methods and research 16S rRNA gene as Streptomyces sp. PR- 32. The results of this characterization suggests a possible new species, but other tests that must be performed. the presence of the NRPS gene of approximately 750 kb was observed. From these results we conclude that Streptomyces sp. PR- 32 is a promising isolated to produce antifungal compounds, it is possible to suggest that the biological activity of this secondary metabolite is regulated by peptide synthase not ribosomal (NRPS).

Dans le cadre d'infections ostéo-articulaire (IOA), l'utilisation de matériels étrangers peut, en cas de contamination, aboutir à la formation d'un biofilm associé à un risque plus important d'échec du traitement et de récidive. Les bactéries sous forme de biofilm sont en effet protégées de l'action du système immunitaire et ont une tolérance plus importante aux antibiotiques. A l'heure actuelle, l'activité des antibiotiques est déterminée par la CMI (Concentration Minimale Inhibitrice), mais cette valeur ne tient pas compte de la forme sessile des bactéries. C'est pourquoi, la société BioFilm Control a développé un nouveau test, l'Antibiofilmogramme®, permettant de déterminer la CMI biofilm (CMIb) reflétant la capacité préventive des antibiotiques sur l'installation des microorganismes en biofilm. L'objectif de ma thèse a été dans un premier temps de participer à la démonstration de la valeur clinique de ce nouveau test dans le cadre des IOA à Staphylococcus aureus. Nous avons pu mettre en place un recueil prospectif et réaliser les premiers essais in vitro. Nos résultats obtenus pour la cloxacillin ont pu par la suite être confirmés sur un modèle in vivo d'infection sur matériel. Dans un second temps, nous avons pu caractériser la capacité de formation de biofilm des souches cliniques en fonction des profils de résistance obtenus en Antibiofilmogramme®. Nous avons pu mettre en évidence des profils différents liés à la clonalité des souches. Enfin, nous avons pu mettre au point une nouvelle méthode de rinçage et de quantification des biofilms pour les modèles en microplaque via l'utilisation de vapeur. Cette approche simple améliore grandement la reproductibilité des résultats et préserve l'intégrité structurelle des biofilms / In the context of Bone and Joint Infections (BJIs), the orthopedic devices are preferential surface for microorganisms to adhere and form biofilm associated with high rates of failures and relapses. Within biofilm, bacteria are protected from the host immune response and are able to survive in the presence of high concentration of antibiotics. The standard Minimal Inhibitory Concentration (MIC) informs on the antibiotic susceptibility of planktonic bacteria, but is not suited for biofilm. The company BioFilm Control developed a new test named Antibiofilmogram® which measures early-stage biofilm growth in presence of antibiotics, and provides a biofilm Minimal Inhibitory Concentration (bMIC). The aim of my PhD research was first to take part in the demonstration of the clinical value of this new test for Staphylococcus aureus BJIs. We established a prospective collection of data and strains and realized the first in vitro assays. Our results for cloxacillin were confirmed in an in vivo model of catheter-associated infection. Second, we characterized the biofilm formation capacity of various clinical isolates based on the Antibiofilmogram® resistance profile. We showed that the biofilm formation capacity is correlated with clonal lineage. Finally, we were able to develop a new method of washing and quantifying biofilms for microplate system using steam. This simple approach preserves the biofilm integrity and lead to highly reproducible data

No description available.

Le complexe d'espèces Fusarium solani regroupe des champignons phytopathogènes également impliqués en pathologie humaine dans des infections parfois profondes et souvent de mauvais pronostic. Dans un premier temps, une méthode de MLST, s'appuyant sur 5 gènes de ménage a donc été développée. Validée sur 51 isolats épidémiologiquement distincts, cette méthode stable et reproductible présente un pouvoir discriminant de 99,1 %. Après comparaison à la technique de référence utilisée en phylogénie, un schéma consensus à 8 loci a été proposé. Dans un second temps, une étude de la sensibilité de ce pathogène à l'amphotéricine B et au voriconazole a été menée par deux techniques d'évaluation des CMI : microdilution CLSI M38-A2 et bandelettes E-test. Devant le paradoxe entre une sensibilité diminuée in vitro au voriconazole et la recommandation de cette molécule pour le traitement curatif de la fusariose humaine, des mécanismes de résistance ont été exploré. L'hypothèse d'un phénomène d'efflux n'a pas été retenue alors que celle d'une modification de la cible, la 14 alpha stérol déméthylase, peut être envisagée après la description de différentes mutations pour les isoformes CYP51A, B et C / Fusarium solani species complex includes phytopathogenic fungi also involved in human infections with poor prognosis. Firstly, MLST method, based on five housekeeping genes has been developed. This method has been validated on 51 isolates epidemiologically distinct, and has been shown to be stable and reproducible and provides a discriminating power of 99.1%. After comparison with the reference technique used in phylogeny, a consensus method with 8 loci has been proposed. Secondly, a study of the susceptibility to amphotericin B and voriconazole has been conducted with two MIC determination methods : CLSI M38-A2 microdilution and E-test. The paradox between decreased susceptibility to voriconazole in vitro and recommendation of this molecule for the curative treatment of Fusarium infections has lead to the exploration of resistance mechanisms. The hypothesis of an efflux phenomenon has not been retained whereas a change in the target, the sterol 14 alpha demethylase may be considered following the description of different mutations on proteins CYP51A, B and C

Mycoplasma (M.) bovis est une bactérie pathogène des bovins, à l'origine de signes cliniques divers, comme des mammites, des arthrites, des otites et des bronchopneumonies, ces dernières étant majoritaires en France. Les mycoplasmoses à M. bovis ont un fort coût économique et leur contrôle impose une importante mobilisation sanitaire et un recours très fréquent à l'antibiothérapie. Peu de données étaient disponibles jusque récemment concernant le typage moléculaire et l'antibiosensibilité des souches françaises de M. bovis. Deux études antérieures à ce travail et réalisées au sein de l'UMR « Mycoplasmoses des ruminants » ont montré que les isolats cliniques de M. bovis collectés en France après 2000 appartiennent à un sous-type moléculaire majoritaire (ST2), très homogène et sont par ailleurs multirésistants à la plupart des familles antibiotiques à l'exception des fluoroquinolones. Ces résultats suggèrent la diffusion sur le territoire national d'un clone unique multirésistant. Le premier objectif de cette étude était de déterminer les mécanismes à la base de la perte de sensibilité aux antibiotiques des isolats français. Dans un deuxième temps, les liens entre les différents sous-types moléculaires, les profils d'antibiosensibilité, les maladies associées et le polymorphisme des gènes cibles des antibiotiques ont été investigués. Cette approche a été déployée pour trois familles d'antibiotiques utilisées en pratique vétérinaire: les macrolides, les tétracyclines et également les fluoroquinolones, quoique récemment classées comme molécules critiques. De façon générale, les mutations identifiées dans les cibles des antibiotiques expliquent à elles seules les phénotypes de résistance observés. Des mutations dans les ARNs ribosomaux, cibles des macrolides et des tétracyclines, ont été observées sur des isolats cliniques dès 1978 et sont devenues systématiques sur tous les isolats collectés après 2000 et appartenant au sous-type ST2 majoritaire. En ce qui concerne les fluoroquinolones, la faible augmentation des CMI (concentrations minimales inhibitrices) mesurée chez la plupart des isolats cliniques récents n'a pas été associée à des mutations des QRDR (« Quinolones Resistance-Determining Regions »). Par contre, des altérations cumulées de façon séquentielle dans ces QRDR, associées à une hausse des CMI, ont été mises en évidence lors d'expériences de sélection in vitro et majoritairement pour des souches appartenant à un sous-type récent minoritaire, ST3, apparemment plus variable et plus apte à fixer les mutations. En 2013, le premier isolat clinique présentant une CMI augmentée aux fluoroquinolones a été isolé: il appartient à ce sous-type ST3. L'ensemble des résultats obtenus montrent que les différents sous-types de M. bovis n'évoluent pas de la même façon vers la résistance. Ce constat ajouté à celui de la multirésistance des isolats récents (ST2 ou ST3) met en exergue l'intérêt de la surveillance (sous-typage et antibiosensibilité) et le suivi de l'évolution des isolats de M. bovis circulant en France. Ce suivi permettrait notamment d'anticiper une éventuelle émergence de la résistance aux fluoroquinolones / Mycoplasma (M.) bovis is a bacterial pathogen for cattle, responsible for various clinical signs, like mastitis, arthritis, otitis and respiratory diseases, the latter being the main syndrome present in France. Mycoplasmoses have a great economic impact and their control entails drastic sanitary measures and a frequent use of antibiotherapy. Few data was available until recently on the molecular subtyping and the antimicrobial susceptibility of the French strains of M. bovis. Two previous studies done in the UMR « Mycoplasmoses des ruminants » proved that clinical isolates collected in France after the year 2000 belonged to one major subtype (ST2), which is very homogeneous, and that they were multiresistant to the main antimicrobial families except fluoroquinolones. These results suggested the diffusion of one unique multiresistant clone on the national territory. The first aim of the present study was to decipher the molecular mechanisms underlying the loss of susceptibility to antimicrobials of the French strains. Secondly the links between the molecular subtypes, the antibiotics susceptibility profiles, the clinical origins and the polymorphisms of the target genes were assessed. This approach was used for 3 antimicrobial families currently used in veterinary medicine: macrolides, tetracyclines and fluoroquinolones, although recently classified as critical. Actually, the point mutations observed in the target genes of the antimicrobials accounted for the observed resistance phenotypes. Some mutations in the ribosomal RNAs, targets of the macrolides and the tetracyclines, were observed in clinical isolates as soon as 1978 and they were generalized in all isolates collected after 2000 and belonging to the major subtype ST2. Concerning the fluoroquinolones, the slight increase in MIC (Minimum Inhibitory Concentration) observed in most of the recent isolates was not associated with mutations in the QRDR (Quinolone Resistance-Determining Regions). However alterations that were associated with increased MICs were highlighted and proved to be sequentially cumulated during experiments of in vitro selection under antimicrobials pressure. This was mainly true for strains belonging to a recent and uncommon subtype, ST3, which is apparently more variable and more able to fix the mutations. In 2013 the first clinical strain showing an increased MIC to fluoroquinolones was isolated and proved to belong to ST3. The whole results of this study showed that the different subtypes did not evolve with the same speed towards resistance. This fact, associated with the multiresistant phenotype of the recent isolates (ST2 or ST3), highlights the urge to monitor (subtyping and antimicrobial susceptibility profiles) and to follow-up the evolution of the isolates of M. bovis circulating in France in order to anticipate a potential emergence of the resistance to fluoroquinolones