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1.
Infect Immun ; 85(10)2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28760936

RESUMO

Activation of caspase-11 by some Gram-negative bacteria triggers the caspase-1/interleukin 1ß (IL-1ß) pathway, independent of canonical inflammasomes. Acinetobacter baumannii is a Gram-negative, conditionally pathogenic bacterium that can cause severe pulmonary infection in hospitalized patients. A. baumannii was revealed to activate canonical and noncanonical inflammasome pathways in bone marrow-derived macrophages (BMDMs). Pulmonary infection of caspase-11-/- mice with A. baumannii showed that caspase-11 deficiency impaired A. baumannii clearance, exacerbated pulmonary pathological changes, and enhanced susceptibility to A. baumannii These data indicate that the caspase-11-mediated innate immune response plays a crucial role in defending against A. baumannii.


Assuntos
Infecções por Acinetobacter/imunologia , Acinetobacter baumannii/imunologia , Caspases/metabolismo , Imunidade Inata , Macrófagos/imunologia , Infecções Respiratórias/imunologia , Infecções por Acinetobacter/enzimologia , Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/metabolismo , Acinetobacter baumannii/patogenicidade , Animais , Caspases/deficiência , Caspases/genética , Inflamassomos/imunologia , Interleucina-1beta/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/microbiologia , Camundongos , Camundongos Knockout , Infecções Respiratórias/enzimologia , Infecções Respiratórias/patologia
2.
J Chemother ; 29(3): 150-153, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27347714

RESUMO

The increase in carbapenem-resistant gram-negative bacteria is a matter of concern due to the limited therapeutic options available. In severe infections caused by these isolates, the rapid detection of the mechanisms of resistance is vital. We described a slightly modified version of the Blue-Carba test, rapid Blue-Carba test, which allows the detection of carbapenemases at 4 h of incubation from a haze of bacterial growth obtained from a positive blood culture. It was able to detect carbapenemase-producing isolates (Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii) with a sensitivity and specificity of 98.1 and 100%, respectively. It is a rapid, easy-to-perform and an inexpensive technique that can be applied to routine laboratories, together with the simultaneous identification by mass spectrometry which would help to screen non-enzymatic carbapenem resistance; this method allows the detection of clinically relevant multidrug-resistant bacteria and the early implementation of accurate therapeutic interventions.


Assuntos
Infecções por Acinetobacter/enzimologia , Bacteriemia/enzimologia , Proteínas de Bactérias/sangue , Farmacorresistência Bacteriana Múltipla , Infecções por Enterobacteriaceae/enzimologia , Infecções por Pseudomonas/enzimologia , Resistência beta-Lactâmica , beta-Lactamases/sangue , Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/crescimento & desenvolvimento , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Argentina , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Carbapenêmicos/metabolismo , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Enterobacteriaceae/crescimento & desenvolvimento , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Hospitais Universitários , Humanos , Inativação Metabólica , Tipagem Molecular , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/isolamento & purificação , Sensibilidade e Especificidade , Fatores de Tempo , beta-Lactamases/genética
3.
PLoS One ; 11(11): e0167068, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27875572

RESUMO

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that causes a wide range of infections including pneumonia, septicemia, necrotizing fasciitis and severe wound and urinary tract infections. Analysis of A. baumannii representative strains grown in Chelex 100-treated medium for hemolytic activity demonstrated that this pathogen is increasingly hemolytic to sheep, human and horse erythrocytes, which interestingly contain increasing amounts of phosphatidylcholine in their membranes. Bioinformatic, genetic and functional analyses of 19 A. baumannii isolates showed that the genomes of each strain contained two phosphatidylcholine-specific phospholipase C (PC-PLC) genes, which were named plc1 and plc2. Accordingly, all of these strains were significantly hemolytic to horse erythrocytes and their culture supernatants tested positive for PC-PLC activity. Further analyses showed that the transcriptional expression of plc1 and plc2 and the production of phospholipase and thus hemolytic activity increased when bacteria were cultured under iron-chelation as compared to iron-rich conditions. Testing of the A. baumannii ATCC 19606T plc1::aph-FRT and plc2::aph isogenic insertion derivatives showed that these mutants had a significantly reduced PC-PLC activity as compared to the parental strain, while testing of plc1::ermAM/plc2::aph demonstrated that this double PC-PLC isogenic mutant expressed significantly reduced cytolytic and hemolytic activity. Interestingly, only plc1 was shown to contribute significantly to A. baumannii virulence using the Galleria mellonella infection model. Taken together, our data demonstrate that both PLC1 and PLC2, which have diverged from a common ancestor, play a concerted role in hemolytic and cytolytic activities; although PLC1 seems to play a more critical role in the virulence of A. baumannii when tested in an invertebrate model. These activities would provide access to intracellular iron stores this pathogen could use during growth in the infected host.


Assuntos
Infecções por Acinetobacter/enzimologia , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/patogenicidade , Proteínas de Bactérias/metabolismo , Genoma Bacteriano , Fosfolipases Tipo C/metabolismo , Células A549 , Infecções por Acinetobacter/genética , Acinetobacter baumannii/genética , Animais , Proteínas de Bactérias/genética , Bovinos , Modelos Animais de Doenças , Cavalos , Humanos , Ovinos , Fosfolipases Tipo C/genética
4.
Acta Crystallogr D Biol Crystallogr ; 70(Pt 3): 760-71, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24598745

RESUMO

ADC-type class C ß-lactamases comprise a large group of enzymes that are encoded by genes located on the chromosome of Acinetobacter baumannii, a causative agent of serious bacterial infections. Overexpression of these enzymes renders A. baumannii resistant to various ß-lactam antibiotics and thus severely compromises the ability to treat infections caused by this deadly pathogen. Here, the high-resolution crystal structure of ADC-1, the first member of this clinically important family of antibiotic-resistant enzymes, is reported. Unlike the narrow-spectrum class C ß-lactamases, ADC-1 is capable of producing resistance to the expanded-spectrum cephalosporins, rendering them inactive against A. baumannii. The extension of the substrate profile of the enzyme is likely to be the result of structural differences in the R2-loop, primarily the deletion of three residues and subsequent rearrangement of the A10a and A10b helices. These structural rearrangements result in the enlargement of the R2 pocket of ADC-1, allowing it to accommodate the bulky R2 substituents of the third-generation cephalosporins, thus enhancing the catalytic efficiency of the enzyme against these clinically important antibiotics.


Assuntos
Acinetobacter baumannii/enzimologia , beta-Lactamases/química , beta-Lactamases/classificação , Infecções por Acinetobacter/enzimologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Apoenzimas/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico/efeitos dos fármacos , Cefalosporinas/farmacologia , Família Multigênica , Especificidade por Substrato/efeitos dos fármacos , beta-Lactamases/genética , beta-Lactamases/metabolismo
5.
Chemotherapy ; 60(4): 250-2, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25925795

RESUMO

BACKGROUND: Acinetobacter spp. is an opportunistic pathogen that has demonstrated increasing relevance in nosocomial infections. Carbapenem-resistant strains have been reported worldwide. METHODS: Since 2014, screening for metallo-ß-lactamases (MBLs) in all Acinetobacter spp. isolates using phenotypic methods and PCR has been implemented at the University Hospital Center Zagreb. RESULTS: The bacterial strain was isolated from the drain of a child hospitalized in a paediatric intensive care unit and identified as Acinetobacter guillouiae using a MALDI TOF automated system. The strain was resistant to meropenem, ceftazidime, cefotaxime, ceftriaxone, cefepime, sulbactam/ampicillin, gentamicin and ciprofloxacin, intermediately susceptible to piperacillin/tazobactam and imipenem, and susceptible to amikacin and colistin. The Hodge test and combined disk test with EDTA were positive. The MICs of meropenem and imipenem were not reduced by cloxacillin, but a small reduction of two dilutions was observed following the addition of sodium chloride, which indicated that OXA-58 was produced. PCR and sequencing of chromosomal DNA from boiled colonies revealed blaOXA-58 and blaNDM-1 genes. CONCLUSION: This is the first report of NDM-1 in Acinetobacter spp. in Croatia. The early detection of these genes will aid in the prevention and in the achievement of adequate infection control by limiting the spread of these organisms.


Assuntos
Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/enzimologia , Acinetobacter/enzimologia , Acinetobacter/isolamento & purificação , beta-Lactamases/biossíntese , beta-Lactamases/isolamento & purificação , Criança , Humanos
6.
Curr Microbiol ; 65(3): 319-29, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22684803

RESUMO

We investigated interactions of human isolates of Acinetobacter calcoaceticus-baumannii complex strains with epithelial cells. The results showed that bacterial contact with the cells as well as adhesion and invasion were required for induction of cytotoxicity. The infected cells revealed hallmarks of apoptosis characterized by cell shrinking, condensed chromatin, and internucleosomal fragmentation of nuclear DNA. The highest apoptotic index was observed for 4 of 10 A. calcoaceticus and 4 of 7 A. baumannii strains. Moreover, we observed oncotic changes: cellular swelling and blebbing, noncondensed chromatin, and the absence of DNA fragmentation. The highest oncotic index was observed in cells infected with 6 A. calcoaceticus isolates. Cell-contact cytotoxicity and cell death were not inhibited by the pan-caspase inhibitor z-VAD-fmk. Induction of oncosis was correlated with increased invasive ability of the strains. We demonstrated that the mitochondria of infected cells undergo structural and functional alterations which can lead to cell death. Infected apoptotic and oncotic cells exhibited loss of mitochondrial transmembrane potential (ΔΨ(m)). Bacterial infection caused generation of nitric oxide and reactive oxygen species. This study indicated that Acinetobacter spp. induced strain-dependent distinct types of epithelial cell death that may contribute to the pathogenesis of bacterial infection.


Assuntos
Infecções por Acinetobacter/enzimologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/patogenicidade , Acinetobacter calcoaceticus/patogenicidade , Apoptose/fisiologia , Caspases/metabolismo , Células Epiteliais/microbiologia , Infecções por Acinetobacter/metabolismo , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Acinetobacter calcoaceticus/fisiologia , Análise de Variância , Aderência Bacteriana/fisiologia , Linhagem Celular , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Microscopia Eletrônica de Transmissão , Espécies Reativas de Oxigênio/metabolismo
7.
Southeast Asian J Trop Med Public Health ; 40(6): 1284-92, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20578463

RESUMO

Multidrug resistant Acinetobacter baumannii has become the most common cause of health care-associated infections at Maharaj Nakhon Si Thammarat Hospital, Thailand. The objective of the study was to detect integrons using PCR-based method from 96 A. baumannii isolates from ventilator-associated pneumonia (VAP) patients and their environment. Antibiotic susceptibility was determined using a disk diffusion technique. Forty-six isolates exhibited integrase genes, with only class I and class II integron detected in 43 and 3 A. baumannii isolates, respectively. Twenty-seven of 52 clinical and 19 of 44 environmental isolates were integron-positive. Detection rate of integron-positive A. baumannii isolated from VAP patients increased from 25% to 83% over the 4 month study period. The majority (91%) of integron-positive A. baumannii showed resistance to 6 or more of 11 antibiotics tested and 72% of class I integron-positive isolates were imipenem-resistant. Thus, class I integron-positive A. baumannii had spread among the VAP patients and into hospital environment, the latter acting as reservoirs of potential pathogens possessing drug resistance genes.


Assuntos
Acinetobacter baumannii/isolamento & purificação , Infecção Hospitalar/microbiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/enzimologia , Infecções por Acinetobacter/genética , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/genética , Técnicas de Tipagem Bacteriana , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/enzimologia , Infecção Hospitalar/genética , Primers do DNA , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Integrases/genética , Integrons/genética , Testes de Sensibilidade Microbiana , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/enzimologia , Pneumonia Associada à Ventilação Mecânica/genética , Reação em Cadeia da Polimerase , Tailândia/epidemiologia , Traqueia/microbiologia
8.
Infect Immun ; 77(3): 1015-21, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19103777

RESUMO

Acinetobacter baumannii is an emerging bacterial pathogen that rapidly develops multiple-drug resistance and is responsible for many nosocomial pulmonary infections. This study investigated the role of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (NOS2) in the host defense against respiratory infection with A. baumannii in mouse models of intranasal A. baumannii infection. gp91(phox-/-) mice showed higher susceptibility to A. baumannii infection than wild-type (WT) C57BL/6 mice, with significantly greater bacterial counts in their lungs (1,000-fold) (P < 0.005) and spleens (10-fold) (P < 0.05). Moreover, all of the gp91(phox-/-) mice succumbed to infection within 48 h. In contrast, only a moderate increase in bacterial burdens was detected in the lungs of NOS2(-/-) mice, and all NOS2(-/-) mice survived infection. Compared to WT mice, the pulmonary influx of inflammatory cells and serum and local inflammatory cytokine/chemokine responses were not obviously impaired at 4 h and were significantly higher at 24 h (P < 0.05) in gp91(phox-/-) mice, but NADPH-deficient neutrophils were unable to control bacterial replication and extrapulmonary dissemination. Thus, NADPH phagocyte oxidase appears to play a crucial role in the neutrophil-mediated host defense against A. baumannii.


Assuntos
Infecções por Acinetobacter/enzimologia , NADPH Oxidases/metabolismo , Infecções Respiratórias/enzimologia , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Camundongos , Camundongos Knockout , NADPH Oxidases/genética , Neutrófilos/imunologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologia
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