Objetivos: Avaliar o perfil de suscetibilidade, a prevalência da produção de AmpC, β-lactamase de espectro estendido (ESBL) e Metalo-β-lactamase (M-βla) em Pseudomonas aeruginosa obtidas de dois hospitais universitários distintos (ISCMPA e HCPA) em Porto Alegre. Em adição, tipagem molecular por PFGE foi realizada entre os isolados produtores de M-βla para avaliar a relação clonal. Métodos: Foi determinada a suscetibilidade de 238 isolados de P. aeruginosa para 8 agentes antimicrobianos, através do teste de disco-difusão, usando agar Müller-Hinton (MH) de acordo com “National Committee for Clinical Laboratory Standards” (NCCLS) . Todos isolados foram avaliados para produção de AmpC com o disco de imipenem (indutor) próximo ao disco de cefepima/ceftazdima (substrato). Um achatamento no halo de cefepime/ceftazidima pela indução da enzima pelo imipenem, indicava resultado positivo para AmpC. Todos isolados forma avaliados para a presença de ESBL através do teste de aproximação de disco com ceftazidima, cefepima, cefotaxima, ceftriaxona e ticarcilina-clavulanato como inibidor de β-lactamase. A produção de M-βla foi determinada através do teste de aproximação de discos de CAZ a discos impregnados com ácido2-mercatopropiônico (2-MPA). As taxas de resistência foram comparadas através do Teste Exato de Fisher. Valor de P<0,05 foi considerado estatisticamente significativo. Análise de macrorestrição com a enzima speI foi realizada em isolados produtores de M-βla. Resultados: As taxas de resistência para todos os agentes foram superiores entre os isolados obtidos na ISCMPA em relação aos do HCPA. A ceftazidima mostrou ser o antibiótico mais efetivo contra os isolados de ambos Hospitais (ISCMPA e HCPA) com taxa de resistência de 25,7% (ISCMPA) e 6,1% (HCPA). A expressão de AmpC foi observada em 190 isolados (83,7% HCPA e 77,1% ISCMPA). Não foi possível detectar a presença de ESBL entre todos as P. aeruginosa avaliadas em ambos hospitais. Foi observada a presença de M-βla em 28 isolados (20,0%) da ISCMPA. Mas não foi detectada M-βla em nenhuma P. aeruginosa do HCPA. A análise de macrorestrição mostrou que 14 de 16 P. aeruginosa Mβla positivas pertenciam a um clone (denominado clone A), e seus subclones. Apenas dois outros clones (B e C) foram identificados em um isolado cada. / Objectives: To evaluate susceptibility profile, the prevalence of extendedspectrum β-lactamases (ESBL) production, AmpC and Metallo-β-lactamases (M-βla) in Pseudomonas aeruginosa obtained from two distinct hospitals (ISCMPA and HCPA) in Porto Alegre, Brazil. In addiction, molecular typing by PFGE was perfomed among isolates producing M-βla in order to evaluate probably clonal relatedness. Methods: The susceptibility of 238 P. aeruginosa to 8 antimicrobial agents was determined by the disk diffusion method, using Müller-Hinton agar (MH) in accordance with “National Committee for Clinical Laboratory Standards” guidelines. All isolates were evaluated for AmpC production with the imipenem disk (strong inducer) near of the cefepime/ceftazidime disk (substrate). A blunting of the cefepime/ceftazidime zone by imipenem-induced enzyme, indicated positive result for AmpC. All isolates were evaluated for ESBL production by disk approximation test with ceftazdime, cefepime, cefotaxime, ceftriaxone plus ticarcillin-clavulanate as inhibitor. M-βla production was determined by disk approximation test with disks containing CAZ and 2-mercatopropionic acid (2-MPA). The results were compared by the Fisher’s Exact Test. Macrorestriction analysis by SpeI, followed by PFGE, was perfomed in isolates M-βla positive. The resistance rates were compared by The Fisher’s Exact Test. P values < 0.05 were considered to be statistically significant. Results: The resistance rates to all antimicrobial agents were higher among isolates obtained from ISCMPA than those obtained from HCPA. The ceftazidime was the more active antibiotic against the isolates in both hospitals with resistance rates of 25,7% (ISCMPA) and 6,1% (HCPA). The derepression of AmpC was observed in 190 isolates (83,7% HCPA and 77,1% ISCMPA). It was not possible to detect the presence of ESBL among all P. aeruginosa evaluated in both hospitals. Positive results for M-βla production were observed in 28 isolates (20,0%) from ISCMPA. But none M-βla production was identified in P. aeruginosa from HCPA. The macrorestriction analysis by PFGE, showed that 14 of 16 M-βla positive P. aeruginosa beloneed to one clone (named clone A) and its subclones.Only two others clones (B and C) were identified in one isolate each.

Le norovirus murin (MNV) est un agent pathogène de la souris récemment découvert et représente le contaminant le plus courant dans les animaleries de Recherche. Néanmoins, les effets de l'infection au MNV sur la recherche biomédicale ne sont pas encore clairs. Nous avons testé l'hypothèse que l'infection au MNV pourrait modifier la réponse immunitaire chez les souris atteintes d'une infection pulmonaire aiguë. Nous rapportons ici que la co-infection avec MNV augmente la survie des souris ayant une infection pulmonaire aiguë à Pseudomonas aeruginosa et diminue la production in vivo et in vitro de cytokines pro-inflammatoires. Nos résultats suggèrent que l'infection au MNV peut profondément modifier les paramètres étudiés dans les modèles classiques d'infection et mener à de fausses conclusions dans ces modèles expérimentaux. / The murine norovirus (MNV) is a recently discovered mouse pathogen, this virus represents the most common contaminant in laboratory mouse colonies. Nevertheless, the effects of MNV infection on biomedical research are still unclear. We tested the hypothesis that MNV infection could alter immune response in mice with acute lung infection. Here we report that co-infection with MNV increases survival of mice with Pseudomonas aeruginosa acute lung injury and decreases in vivo and in vitro production of pro-inflammatory cytokines. Our results suggest that MNV infection can deeply modify the parameters studied in conventional models of in-fection and lead to false conclusions in experimental models.

A resistência aos carbapenêmicos em amostras de Pseudomonas aeruginosa e Acinetobacter spp aumentou na última década. Vários surtos causados por esses agentes já foram descritos no Brasil. O presente estudo comparou métodos fenotípicos de triagem de carbapenemase em P. aeruginosa e Acinetobacter spp. isolados de hemoculturas de pacientes internados no HC-FMUSP. Foram estudados 108 isolados de P. aeruginosa identificados por sistema automatizado Vitek® e 50 isolados Acinetobacter spp. identificados pelo método miniaturizado API20NE. A determinação inibitória mínima dos carbapenêmicos foi realizada pela técnica de microdiluição em caldo e a tipagem molecular pela técnica de eletroforese em campo pulsado (PFGE). Os genes codificadores de carbapenemase foram identificados por meio da técnica de reação em cadeia da polimerase (PCR) e foi avaliada a hidrólise de imipenem de todos os isolados positivos para esses genes. Sensibilidade, especificidade, valor preditivo negativo e positivo dos testes fenotípicos foram calculados usando como padrão-ouro a detecção dos genes codificadores das carbapenemases por PCR. Nos isolados de Acinetobacter spp, foram pesquisados os genes das oxacilinases, dos quais quarenta e nove (98%) apresentaram pela técnica de PCR genes codificadores da enzima Oxa-51-like, sendo que um isolado não apresentou essa enzima e após sequenciamento do gene codificador da porção 16S do RNA ribossomal, foi considerado da espécie A. calcoaceticus. Em trinta e oito (76%) dos isolados foi detectado o gene blaOXA-143, em nove (18%) foi detectado o gene blaOXA-23, sendo que sete desses isolados pertenciam ao mesmo clone. Apenas cinco (10%) isolados de Acinetobacter spp apresentaram o gene blaIMP-1. Para os isolados de P. aeruginosa o gene blaSPM-1 foi o mais frequente sendo identificado em vinte e um (19,4%) dos isolados e quatro (3,7%) foi identificado com o gene blaVIM-2. Nove dos vinte e um isolados positivo para gene blaSPM-1, apresentaram a mesma clonalidade. O gene codificador blaGES-5 foi encontrado em quatro (3,7%) dos isolados de P. aeruginosa. Dos vinte quatro isolados P. aeruginosa que apresentaram gene codificador da M?L, apenas um isolado não hidrolisou IMI entre os Acinetobacter spp e apenas dois dos cincos isolados positivos para o gene codificador de M?L, hidrolisaram o IMI e apresentaram inibição com o EDTA. Dos vários testes fenotípicos realizados, os melhores resultados foram observados com Etest® M?L para ambos microrganismos com sensibilidade de 100%, mas esse teste foi pouco específico. Para os isolados de Acinetobacter spp o melhor resultado foi observado com o teste de aproximação de disco de IMI com disco de ABM, que apresentou sensibilidade de 100% e especificidade de 71% e para P. aeruginosa foi a aproximação de disco de CAZ com um disco de EDTA, que apresentou sensibilidade de 48% e especificidade de 93%. O presente estudo verificou que não existe um único teste fenotípico que consiga identificar carbapenemases nesses isolados e que a performace dos testes varia de acordo com as carbapenemases encontradas / Carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter spp increased in the last decade. Several outbreaks caused by these agents resistant to carbapenems have been reported in Brazil. This study compared several phenotypic methods for screening of carbapenemase in P. aeruginosa and Acinetobacter spp isolated from blood cultures of hospitalized patients in HCFMUSP. One hundred and eight isolates were studied of P. aeruginosa identified by the automated system Vitek® and fifty isolates Acinetobacter spp identified by the API20NE method miniaturized. The determination of cabapenem minimum inhibitory was performed by the microdilution broth. Molecular typing was performed using the technique of pulsed field gel electrophoresis (PFGE). Genes encoding carbapenemase were identified by the technique of polymerase chain reaction (PCR) and was evaluated by hydrolysis of imipenem of all the positives isolates. Sensitivity, specificity, positive and negative predictive value of phenotypic tests were calculated using as the gold standard the detection of genes encoding carbapenemases by PCR. Oxacilinases genes were evaluated in isolates of Acinetobacter spp, of which forty-nine (98%) exhibited by PCR enzyme- encoding gene OXA-51-like, and the one isolate that did not show this enzyme, after gene sequencing encoding portion 16S ribosomal RNA was considered the species A. calcoaceticus. In thirty-eight (76%) isolates the gene OXA-143- like was detected and seven belonged to the same clone. Only five (10%) isolates of Acinetobacter spp showed the gene blaIMP-1. For the isolates of P. aeruginosa, gene blaSPM-1 was the most frequent being present in twenty-one (19,4%) isolates and four (3,7%) was identified with the gene blaVIM-2. Nine of the twenty-one isolates positive for gene blaSPM-1, showed the same clonality. The gene encoding blaGES-5 was found in four (3,7%) isolates of P. aeruginosa. Among the twenty-four isolates P. aeruginosa harboring M?L, not only one isolated hydrolyzed IMI, between Acinetobacter spp two of five isolates harboring M?L hydrolyzed IMI that was inhibited by EDTA. Of the various phenotypic tests conducted, the best results were observed for Etest® for both micro-organisms with sensitivity 100%, but this test was not specific. For the isolates of Acinetobacter spp best result was observed in the nearest IMI disk a disk of ABM, which had a sensitivity of 100% and specificity of 71% and for P. aeruginosa was approaching CAZ disk with a disk EDTA which had a sensitivity of 48% and specificity of 93%. This study verified that there is no single phenotypic test which can identify those isolates carbapenemases and that the performance of the tests various according to carbapenemases found

Opções terapêuticas para tratar infecções por Pseudomonas aeruginosa são limitadas por seus diversos mecanismos de resistência, que podem ou não ser detectados no laboratório clínico. Um fenótipo observado na rotina laboratorial é o surgimento de subpopulações resistentes a partir de uma população sensível aos antimicrobianos – heteroresistência. Em P. aeruginosa esse fenômeno já foi investigado para carbapenêmicos, porém, em relação à polimixina B, não há dados literários. Objetivamos avaliar a heteroresistência à polimixina B em dois grupos de P. aeruginosa, um sensível e outro resistente aos carbapenêmicos. Cento e vinte e quatro isolados de P. aeruginosa foram obtidos, aleatoriamente, no Hospital de Clínicas de Porto Alegre em 2011. O perfil de susceptibilidade aos antimicrobianos, disco difusão e microdiluição em caldo – CIM (determinação da concentração inibitória mínima) para polimixina B, foi realizada conforme o Clinical Laboratory Standard Institute (CLSI) 2011. Isolados resistentes aos carbapenêmicos foram avaliados para CIM dos carbapenêmicos e cefalosporinas, e para pesquisa fenotípica e genotípica de metalo-β-lactamase (MβL). Um total de 24/124 isolados foi separado em dois grupos, um sensível (grupo S) e outro resistente (grupo R) aos carbapenêmicos (imipenem e/ou meropenem) para investigação da heteroresistência a polimixina B. Realizou-se ensaio de heteroresistência em duplicata através de diluições seriadas, partindo de uma suspensão de 0,5 de MacFarland e inoculadas em Agar Mueller Hinton com concentrações crescentes de polimixina B (0; 0,5; 1; 2; 4 e 8μg/mL). Após 5 dias de passagem em meio sem antibiótico, foi determinada a CIM dos isolados que cresceram na concentração mais alta de polimixina B. O perfil de análise populacional (PAP) foi definido pela razão do número de unidades formadoras de colônia (UFC) da placa com maior concentração de polimixina B onde houve crescimento bacteriano, pelo número de UFC da placa sem antibiótico. Foram consideradas heteroresistentes amostras que apresentaram subpopulações com crescimento em concentração de polimixina B ≥ 2 μg/mL. Amostras com subpopulações com crescimento em concentração de polimixina B superiores duas vezes ao CIM original, mas < 2 μg/mL, foram classificadas como heterogêneas. O resultado do disco difusão indicou heterogeneidade de suscetibilidade, sendo que gentamicina e imipenem foram os antibióticos com maior percentual de resistência e aztreonam e ciprofloxacino apresentaram os maiores perfis de sensibilidade. Todos os isolados foram sensíveis à polimixina B, com CIM50 e CIM90 de 1μg/mL e 2μg/mL, respectivamente. Trinta e sete isolados (30%; 37/124) apresentaram resistência aos carbapenêmicos. Quatro amostras foram positivas para MβL no teste fenotípico, sendo que o gene blaIMP foi idenficado nestas amostras. O grupo S não apresentou subpopulação heteroresistente, porém 3 isolados apresentaram subpopulação heterogênea. A freqüência do PAP no grupo S variou entre 2,1x10-4 a 4,0x10-7. O grupo R apresentou uma amostra heteroresistente e 6 isolados apresentaram subpopulação heterogênea, a freqüência do PAP variou entre 2,6x10-4 a 2,0x10-7. Os resultados deste estudo indicam baixa ocorrência de heteroresistência à polimixina B em amostras de P. aeruginosa tanto resistentes quanto sensíveis aos carbapenêmicos. No entanto, diversas amostras apresentaram subpopulações heterogêneas (CIM aumentada para a polimixina B), o que poderia explicar eventuais falhas terapêuticas durante o tratamento. / Therapeutic options to treat infections caused by Pseudomonas aeruginosa are limited because of their different resistance mechanisms that can be or don't be detected in the clinical laboratory. A phenotype that has been observed in our laboratory is the emergence of resistant subpopulations from a population sensitive to antibiotics - a phenomenon named heteroresistance. In P. aeruginosa this phenomenon has been investigated for carbapenems, however, in relation to the polymyxin B no data in the literature. We investigate the heteroresistance and polymyxin B into two groups P. aeruginosa, one sensitive and second resistant to carbapenems. One hundred twenty-four strains of P. aeruginosa were obtained randomly at the Hospital de Clinicas de Porto Alegre in 2011. The Antimicrobial Susceptibility Testing (Disk-difusion and the microdiluition broth, with determination of minimum inhibitory concentration (MIC) for polymyxin B, was performed according the Clinical Laboratory Standards Institute (CLSI), 2011. Isolates resistant to carbapenems were evaluated for MIC of carbapenems and cephalosporins, also for phenotypic and genotypic metallo-β-lactamase (MβL). A total of 24/124 strains were separated in two groups, one sensitive (S group) and other resistant (R group) to carbapenems (imipenem and / or meropenem) for investigation of heteroresistance polymyxin B. The assay was performed in duplicate heteroresistance through serial dilutions, starting from a 0.5 MacFarland suspension and inoculated into Mueller Hinton Agar with increasing concentrations of polymyxin B (0; 0,5; 1; 2; 4 e 8μg/mL). After 5 days of passage in medium without antibiotics, was determined the MIC of the isolates that grew at the highest concentration of polymyxin B. The population analysis profile (PAP) was defined as the ratio of the number of colony forming units (CFU) on the card with the highest concentration of polymyxin B in which bacterial growth, the number of CFU plate without antibiotic. We considered heteroresistant samples that showed subpopulations with growth in concentration of polymyxin B ≥ 2 mg / mL. Samples with subpopulations growing at higher concentration of polymyxin B twice CIM original, but <2 mg / mL were classified as heterogeneous. The result of AST indicated heterogeneity of susceptibility, and gentamicin and imipenem were the highest percentage with antibiotic resistance and aztreonam and norfloxacin showed the highest sensitivity profiles. All isolates were susceptible to polymyxin B, with CIM50 and CIM90 of 1μg/mL and 2μg/mL, respectively. Thirty-seven isolates (30%; 37/124) were resistant to carbapenems. Four samples were positive for the phenotypic test to MβL and the blaIMP gene was indentificated in this samples. The S group showed no subpopulation heteroresistente, but 3 isolates showed heterogeneous subpopulation. The frequency of PAP in group S varied between 2,0x10-4 to 4,0x10-7. The group R provided a sample heteroresistant and 6 isolates showed heterogeneous subpopulation, the frequency of PAP varied between 2,6x10- 4 a 2,0x10-7. The results of this study indicate a low occurrence of heteroresistance to polymyxin B in samples of P. aeruginosa so resistant assensitive to carbapenems. However, several samples showed heterogeneous subpopulations (MIC increased to polymyxin B) which could explain possible treatment failure during treatment.

L'utilisation de virus de bactéries ou bactériophages pourrait être un complément efficace à l’antibiothérapie. Mon travail a porté sur la caractérisation de bactériophages dirigés contre l’espèce Pseudomonas aeruginosa, pathogène opportuniste responsable d'infections des voies respiratoires des patients atteints de mucoviscidose.J'ai tout d'abord déterminé la sensibilité des souches mucoviscidosiques au Pyophage (un cocktail de phages thérapeutiques Géorgien) et identifié six phages lytiques de quatre genres différents. Environ 15% des souches sont résistantes au Pyophage. Ensuite, en utilisant les souches cliniques multi-résistantes aux phages comme bactérie d’enrichissement, 32 phages ont été obtenus à partir des eaux usées de France et Côte d’Ivoire. Tous les phages analysés sont caudés et distribués au sein de dix genres parmi lesquels six exclusivement lytiques. J'ai identifié des souches bactériennes qui demeurent insensibles à tous les phages. J'ai montré que le système CRISPRs-Cas n'est pas associé à la résistance des souches aux phages lytiques. / The use of viruses of bacteria commonly called bacteriophages could constitute an efficient complement to antibiotics. During my PhD, I have characterized phages infecting the opportunistic pathogen Pseudomonas. aeruginosa, responsible for lung infections in cystic fribrosis patients. Firstly, I investigated the efficiency of Pyophage (a cocktail of phages therapeutic Georgian) on clinical P. aeruginosa strains and recovered six lytic phages from four different genus. The Pyophage appears to be unactive on approximately 15% of clinical strains. Secondly, and using multi-phages resistant strains as enrichment bacteria, 32 phages were isolated from waste water of France and Côte d’Ivoire. All phages are tailed and distributed within ten different genus including six exclusively lytic. I identified bacterial strains which remain insensitive to all phages. I also demonstrated that the CRISPRs-cas system plays no role in the resistance of strains to lytic phages.

Reproduction de : Thèse de doctorat : Physiologie, Biologie des organismes, populations, interactions : Lille 2 : 2008. / Résumé en français et en anglais. Titre provenant de l'écran-titre. Bibliogr. f. 143-175.

The Gram-negative bacterium Pseudomonas aeruginosa is a notorious opportunistic pathogen of individuals with the genetic disease cystic fibrosis (CF). Pseudomonas aeruginosa establishes a chronic infection within the CF lung, where the sputum accumulation characteristic of CF provides a complex and copious growth substrate. P. aeruginosa can grow to high densities in vivo (>10⁹ cells/ml lung sputum), and exacerbations associated with P. aeruginosa high density in vivo growth are primary contributors to CF morbidity and mortality. Surprisingly little is known about the catabolic processes that underlie P. aeruginosa in vivo growth. Unfortunately, nutritional modeling of the CF lung environment in animal models is difficult, as current animal models fail to mimic the sputum accumulation characteristic of CF. In this dissertation, I describe the use of expectorated CF sputum as a P. aeruginosa in vitro growth medium. Using global expression analysis, I show that P. aeruginosa up-regulates genes important for amino acid and lactate metabolism during growth in CF sputum as compared to a laboratory medium. P. aeruginosa also demonstrates enhanced production of the cell-cell communication signal 2-heptyl-3-hydroxy-4-quinolone (the Pseudomonas quinolone signal, PQS), a critical regulator of virulence factor production, during growth in CF sputum. Further, I use chemical analyses of CF sputum samples to develop a defined, synthetic medium that can be used to nutritionally model in vivo conditions. Using this medium, I show that PQS biosynthesis and aromatic amino acid metabolism are intimately linked and that cell-cell communication mediated by PQS is strikingly dependent upon the growth environment of P. aeruginosa. In addition, I demonstrate that P. aeruginosa preferentially consumes specific carbon sources present in the CF sputum milieu during rapid growth. I also describe the use of in vivo-relevant nutrient concentrations to evaluate the potential for P. aeruginosa anaerobic growth in CF sputum. Finally, I describe the purification and characterization of the aromatic amino acid-responsive transcriptional regulator PhhR and discuss its potential role in regulation of P. aeruginosa in vivo carbon substrate preference. / text

This work was undertaken with the objective of isolating and characterising the bdh gene of P. aeruginosa PAOI. Isolation of the bdh gene was initially attempted by PCR amplification and then by heterologous complementation of E. coli (LS5218) and S. meliloti (Rm11107) strains unable to catabolise 3-hydroxybutyrate. Three classes of plasmids were isolated. Class I comprised two plasmids, p5218-02 and p5218-07, isolated via complementation of LS5218, which were capable of complementing both LS5218 and Rm11107 for growth on 3-hydroxybutyrate. 3-hydroxybutyrate dehydrogenase (BDH) activity was not detected in an extract of LS5218 (p5218-02). The sole 3.6-kb EcoRI fist was partially sequenced and found to have three putative open reading frames (ORF). ORF 1 is homologous to the fusE gene of E. coli. We hypothesised that p5218-02 encodes an enzyme capable of degrading 3 hydroxybutyrate, but does not encode the bdh gene. Plasmids of class II (p30065) and class III (p30066) were isolated via complementation of Rm11107. Significant BDH activity was detected in an extract of Rm11107 (p30066), but not in Rm11107, leading to the hypothesis that p30066 carries the bdh gene.

Disertacijos tema: Potencialių hospitalinės pneumonijos sukėlėjų Pseudomonas aeruginosa ir Klebsiella pneumoniae patogeniškumo veiksniai bei jų įtaka ligos eigai Darbo tikslas -ištirti Pseudomonas aeruginosa ir Klebsiella pneumoniae padermių, kolonizavusių apatinius kvėpavimo takus ar sukėlusių hospitalinę pneumoniją, patogeniškumo veiksnius ir jų įtaką hospitalinės pneumonijos eigai. Uždaviniai: • Ištirti hospitalinę pneumoniją sukėlusių ar apatinius kvėpavimo takus kolonizavusių Pseudomonas aeruginosa padermių patogeniškumo veiksnius - atsparumą serumo baktericidiniam poveikiui, gebėjimą įsiskverbti į kvėpavimo takų epitelio ląsteles, atsparumą antibiotikams ir O serogrupinę priklausomybę. • Įvertinti Pseudomonas aeruginosa padermių patogeniškumo veiksnių tarpusavio sąsajas. • Ištirti Klebsiella pneumoniae padermių, sukėlusių hospitalinę pneumoniją ar kolonizavusių apatinius kvėpavimo takus, gebėjimą gaminti plataus spektro beta laktamazes bei atsparumą antibiotikams. • Įvertinti Pseudomonas aeruginosa ir Klebsiella pneumoniae padermių patogeniškumo veiksnių įtaką hospitalinės pneumonijos eigai. Darbas yra pirmas Lietuvoje, kurio metu ne tik nustatytas Pseudomonas aeruginosa patogeniškumo veiksnys – atsparumas serumo baktericidiniam poveikiui, bet ir įvertinta galima šį patogeniškumo veiksnį įgijusių Pseudomonas aeruginosa padermių įtaka hospitalinės pneumonijos vystytis bei ligos eigai. Pirmą kartą apskritai vertintas Pseudomonas aeruginosa padermių gebėjimas įsiskverbti į... [toliau žr. visą tekstą] / The aim of the study: To examine pathogenicity factors of Pseudomonas aeruginosa and Klebsiella pneumoniae strains, colonizing lower respiratory tract or causing hospital-acquired pneumonia, and to evaluate their influence on the course of hospital-acquired pneumonia. Objectives of the sudy: 1. To examine pathogenicity factors – resistance to serum bactericidal activity, ability to penetrate epithelial cells of the respiratory tract, dependence of O serogroup, and resistance to antibiotics – of Pseudomonas aeruginosa strains, colonizing lower respiratory tract or causing hospital-acquired pneumonia. 2. To evaluate the relationship between pathogenicity factors of Pseudomonas aeruginosa strains. 3. To examine the ability of Klebsiella pneumoniae strains, colonizing lower respiratory tract or causing hospital-acquired pneumonia, to produce extended-spectrum beta-lactamases and resistance of these pathogen to antibiotics. 4. To evaluate the influence of pathogenicity factors of Pseudomonas aeruginosa and Klebsiella pneumoniae strains on the course of hospital-acquired pneumonia. Such work is first in Lithuania, because we determined not only pathogenicity factors of Pseudomonas aeruginosa – i.e., resistance to bactericidal activity of serum, but also evaluated possible influence of Pseudomonas aeruginosa strains, having this pathogenicity factor, on hospital-acquired pneumonia development and outcome. Therefore, the ability of Pseudomonas aeruginosa strains to invasive into... [to full text]

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.