Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 152
Filtrar
1.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31548324

RESUMO

Acinetobacter baumannii is an opportunistic bacterial pathogen capable of causing a variety of infections, including pneumonia, sepsis, wound, and burn infections. A. baumannii is an increasing threat to public health due to the prevalence of multidrug-resistant strains, leading the World Health Organization to declare A. baumannii a "Priority 1: Critical" pathogen, for which the development of novel antimicrobials is desperately needed. Zinc (Zn) is an essential nutrient that pathogenic bacteria, including A. baumannii, must acquire from their hosts in order to survive. Consequently, vertebrate hosts have defense mechanisms to sequester Zn from invading bacteria through a process known as nutritional immunity. Here, we describe a Zn uptake (Znu) system that enables A. baumannii to overcome this host-imposed Zn limitation. The Znu system consists of an inner membrane ABC transporter and an outer membrane TonB-dependent receptor. Strains of A. baumannii lacking any individual Znu component are unable to grow in Zn-starved conditions, including in the presence of the host nutritional immunity protein calprotectin. The Znu system contributes to Zn-limited growth by aiding directly in the uptake of Zn into A. baumannii cells and is important for pathogenesis in murine models of A. baumannii infection. These results demonstrate that the Znu system allows A. baumannii to subvert host nutritional immunity and acquire Zn during infection.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Proteínas de Transporte de Cátions/genética , Zinco/metabolismo , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL
2.
Autops. Case Rep ; 9(3): e2019106, July-Sept. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1016813

RESUMO

Acinetobacter baumannii has emerged as a pan-resistant superbug causing fatal infections in vulnerable patients. This report is the case of an immunosuppressed transplant patient with a fatal pneumonia due to pan-resistant Acinetobacter baumannii. Alternative therapy for resistant Acinetobacter infection is currently the subject of intense interest and research. This report illustrates the features of this type of emerging infectious disease and reviews some of the novel approaches to treatment.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Acinetobacter/patologia , Farmacorresistência Bacteriana , Pneumonia/complicações , Autopsia , Infecções por Acinetobacter/terapia , Evolução Fatal
3.
Genes (Basel) ; 10(4)2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965610

RESUMO

Quorum sensing (QS) is a cell-to-cell communication system that uses autoinducers as signaling molecules to enable inter-species and intra-species interactions in response to external stimuli according to the population density. QS allows bacteria such as Acinetobacter baumannii to react rapidly in response to environmental changes and hence, increase the chances of survival. A. baumannii is one of the causative agents in hospital-acquired infections and the number of cases has increased remarkably in the past decade. In this study, A. baumannii strain 863, a multidrug-resistant pathogen, was found to exhibit QS activity by producing N-acyl homoserine lactone. We identified the autoinducer synthase gene, which we named abaI, by performing whole genome sequencing analysis of A. baumannii strain 863. Using high resolution tandem triple quadrupole mass spectrometry, we reported that abaI of A. baumannii strain 863 produced 3-hydroxy-dodecanoyl-homoserine lactone. A gene deletion mutant was constructed, which confirmed the functionality of abaI. A growth defect was observed in the QS-deficient mutant strain. Transcriptome profiling was performed to determine the possible genes regulated by QS. Four groups of genes that showed differential expression were discovered, namely those involved in carbon source metabolism, energy production, stress response and the translation process.


Assuntos
Infecções por Acinetobacter/genética , Acinetobacter baumannii/genética , Proteínas de Bactérias/genética , Fatores de Transcrição/genética , Transcriptoma/genética , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/patogenicidade , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Infecção Hospitalar/genética , Infecção Hospitalar/microbiologia , Infecção Hospitalar/patologia , Farmacorresistência Bacteriana Múltipla , Genoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutagênese , Percepção de Quorum/genética , Recombinação Genética/genética
4.
Surg Infect (Larchmt) ; 20(6): 460-464, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30942663

RESUMO

Background: Post-operative central nervous system infection (PCNSI) caused by multi-drug-resistant/extensively drug-resistant (MDR/XDR) Acinetobacter baumannii is a severe complication. This study aimed to analyze the clinical presentation and treatment of this disorder. Patients and Methods: A retrospective study that recruited patients having PCNSI caused by MDR/XDR Acinetobacter baumannii was performed at our institute. The patients' demographic information and clinical data were recorded and analyzed. To analyze treatment, we assigned patients to different groups according to whether they had intraventricular/intrathecal injection of antibiotic agents or cerebrospinal fluid (CSF) drainage therapy. Results: Twenty-four patients were included. The risk factors were classified into two categories: environmental factors (intensive care unit stay, tracheal intubation or tracheotomy, positive culture of MDR/XDR Acinetobacter baumannii from other samples) or infectious approaches (CSF drainage, incision CSF leakage). Cerebrospinal fluid sterilization was achieved in 13 patients (54.2%) and the 30-day mortality was 50%. In the seven patients having intraventricular/intrathecal injection of antibiotic agents, the CSF sterilization rate was 71.4% (5/7) and 30-day mortality was 28.6% (2/7), compared with 47.1% (8/17; p = 0.27) and 58.8% (10/17; p = 0.18) in patients having only intravenous antibiotic agents. In 19 patients having CSF drainage therapy for PCNSI, the CSF sterilization rate was 63.2% (12/19) and 30-day mortality was 42.1% (8/19) compared with 20% (1/5; p = 0.08) and 80% (4/5; p = 0.13) in the remaining patients. Conclusions: The risk factors for PCNSI caused by Acinetobacter baumannii can be classified in two categories: environmental factors or infectious approaches. Both intraventricular/intrathecal injection of antibiotic agents and CSF drainage are helpful for CSF sterilization.


Assuntos
Infecções por Acinetobacter/patologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Infecções do Sistema Nervoso Central/patologia , Farmacorresistência Bacteriana Múltipla , Procedimentos Neurocirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/patologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
5.
Curr Microbiol ; 76(6): 723-731, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989324

RESUMO

Successful clones of Acinetobacter baumannii cause a variety of nosocomial infections through serum resistance, biofilm formation, and antimicrobial resistance as virulence capabilities. Fifty clinical isolates of multidrug-resistant (MDR) A. baumannii were analyzed for clonal relatedness, serum resistance, biofilm formation, and in vivo assays. Furthermore, some virulence genes, sequence variation of ompA, and its expression were studied. The MLST (multilocus sequence typing) results showed that there were three sequence types among MDR isolates including ST2 (64%, 32/50), ST513 (30%, 15/50), and ST1 (6%, 3/50). The data showed that the clinical isolates recovered from sputum had mostly high biofilm-formation capacity, while isolates recovered from host interior fluids had high serum resistance. The results of PCR assays and in silico analysis represented patterns of virulence genes and even ompA sequence variations among MDR isolates which were clonally dependent. While quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that bacteremia-producing strains in C57/BL6 mice significantly overexpress ompA (P < 0.05) and have a direct relation with the level of IL-6 in bloodstream of mice. Moreover, the expressions of ompA among indistinguishable clones (ST2 or ST513) were clonally independent.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/crescimento & desenvolvimento , Acinetobacter baumannii/patogenicidade , Proteínas da Membrana Bacteriana Externa/biossíntese , Farmacorresistência Bacteriana Múltipla , Tipagem de Sequências Multilocus , Fatores de Virulência/biossíntese , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/classificação , Acinetobacter baumannii/isolamento & purificação , Animais , Biofilmes/crescimento & desenvolvimento , Atividade Bactericida do Sangue , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Genótipo , Humanos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Sepse/microbiologia , Sepse/patologia , Escarro/microbiologia , Virulência
6.
Surg Infect (Larchmt) ; 20(4): 292-297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785859

RESUMO

Background: Intra-cranial infection with Acinetobacter baumannii is a tough problem because of the presence of multi-resistance and poor drug penetration through the blood-brain barrier. Such intra-cranial infections can lead to serious complications and death. We retrospectively analyzed the culture results and clinical characteristics of patients with intra-cranial infections in our hospital and suggested intravenous (IV) meropenem and intra-thecal (IT) amikacin therapy may be effective in the management of A. baumannii infection. Case presentation: We reported four cases of post-neuro-surgical A. baumannii intra-cranial infection whose clinical futures were high fever and consciousness disturbance. Our patients were treated successfully with IV meropenem and IT amikacin. Conclusion: We presented our cases of pandrug-resistant A. baumannii intra-cranial infection that was managed successfully with a systemic provision of IV meropenem and IT amikacin. Therefore, these cases exemplify that systemic administration of IV meropenem and IT amikacin can be a good therapeutic option against A. baumannii intra-cranial infection when colistin is not available.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções do Sistema Nervoso Central/tratamento farmacológico , Meropeném/administração & dosagem , Procedimentos Neurocirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/isolamento & purificação , Administração Intravenosa , Adulto , Idoso , Infecções do Sistema Nervoso Central/patologia , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/patologia , Resultado do Tratamento
7.
Methods Mol Biol ; 1946: 271-287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798563

RESUMO

Multidrug-resistant A. baumannii are important Gram-negative pathogens causing persistent wound infections in both wounded and burned victims, which often result in secondary complications such as delayed wound healing, skin graft failure, and sometimes more serious outcomes such as sepsis and amputation. The choice of antibiotics to remediate these A. baumannii infections is becoming limited; and therefore, there has been a renewed interest in the research and development of new antibacterials targeting this pathogen. However, the evaluation of safety and efficacy is made more difficult by the lack of well-established in vivo models. This chapter describes established rodent and large animal models that have been used to investigate and develop treatments for A. baumannii skin and soft tissue infections.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Dermatite/microbiologia , Infecções dos Tecidos Moles/microbiologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/ultraestrutura , Animais , Biópsia , Dermatite/patologia , Modelos Animais de Doenças , Feminino , Imunofluorescência , Camundongos , Infecções dos Tecidos Moles/patologia , Suínos
8.
Methods Mol Biol ; 1946: 289-305, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798564

RESUMO

Acinetobacter baumannii is a Gram-negative opportunistic pathogen and a leading cause of ventilator-associated pneumonia. Murine models of A. baumannii lung infection allow researchers to experimentally assess A. baumannii virulence and host response. Intranasal administration of A. baumannii models acute lung infection. This chapter describes the methods to test A. baumannii virulence in a murine model of lung infection, including assessing the competitive index of a bacterial mutant and the associated inflammatory responses.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Pneumonia Bacteriana/microbiologia , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/patogenicidade , Doença Aguda , Animais , Carga Bacteriana , Biópsia , Modelos Animais de Doenças , Citometria de Fluxo , Imunidade , Imuno-Histoquímica , Camundongos , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/patologia , Virulência
9.
Artigo em Inglês | MEDLINE | ID: mdl-30617096

RESUMO

Colistin resistance in Acinetobacter baumannii is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. A mutation in pmrB was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, and ΔL9-G12). Increased expression of pmrC was shown by semi-quantitative reverse transcription-PCR (qRT-PCR) for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of pmrAB carrying the short amino acid deletion ΔL9-G12 into a pmrAB knockout strain resulted in increased pmrC expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain specificity of this colistin resistance mechanism. Of note, a mutation in the pmrC homologue eptA and a point mutation in ISAba1 upstream of eptA were associated with colistin resistance and increased eptA expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a Galleria mellonella infection model. Although the mutations in pmrB were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain specific.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Fatores de Transcrição/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/patogenicidade , Animais , Modelos Animais de Doenças , Humanos , Lipídeo A/metabolismo , Testes de Sensibilidade Microbiana , Mariposas/microbiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-30373797

RESUMO

Herein, we describe the in vivo efficacy of human-simulated WCK 5222 (cefepime-zidebactam) exposure against carbapenem-resistant Acinetobacter baumannii strains in a neutropenic murine thigh infection model. Five of the six isolates examined expressed OXA-23 or OXA-24. WCK 5222, despite showing MICs of 16 to 64 mg/liter, produced remarkable in vivo activity; human-simulated exposure showed a decline in the bacterial burden for all isolates (mean reduction, -2.09 ± 1.01 log10 CFU/thigh), while a lack of activity was observed with cefepime and zidebactam monotherapies.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Cefalosporinas/farmacologia , Ciclo-Octanos/farmacologia , Neutropenia/tratamento farmacológico , Resistência beta-Lactâmica/efeitos dos fármacos , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/crescimento & desenvolvimento , Animais , Carga Bacteriana/efeitos dos fármacos , Carbapenêmicos/farmacologia , Cefepima/farmacologia , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Neutropenia/microbiologia , Neutropenia/patologia , Piperidinas/farmacologia , Coxa da Perna/microbiologia , Resultado do Tratamento , Resistência beta-Lactâmica/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo
11.
Clin Microbiol Infect ; 25(4): 516.e1-516.e4, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30583061

RESUMO

OBJECTIVES: Acinetobacter baumannii can cause severe nosocomial and community-acquired pneumonia. To study the pathogenesis of A. baumannii and to develop new treatments, appropriate mouse models are needed. Most reported mouse models of pulmonary A. baumannii infection are non-lethal or require mouse immunosuppression to enhance infection. These models are not suitable for studying host immune responses or evaluating immunotherapies. METHODS: The virulence of 30 clinical isolates was assessed in mice. The most virulent isolate, SJZ24, was selected to develop a pneumonia model in immunocompetent mice. The cytokine mRNA expression in the lung was assessed with real-time PCR. The cell infiltration in bronchoalveolar lavage fluid (BALF) after SJZ24 infection was determined by flow cytometry. Vaccine efficacy was assessed using this model. RESULTS: Intratracheal inoculation of SJZ24 (5 × 107 CFU) resulted in death in 100% of the mice (5/5). SJZ24-infected mice showed high bacterial burdens in blood and organs as well as severe lung-tissue damage. Infection with SJZ24 induced increased inflammatory cytokine expression in the lung and increased neutrophil infiltration in BALF. Immunization with inactivated whole cells of SJZ24 showed 100% protection (5/5) against A. baumanni infection in this model. CONCLUSIONS: We established a lethal pneumonia model in immunocompetent mice with hypervirulent A. baumannii isolate SJZ24. This model can be used to study the immune response to A. baumannii infection and to evaluate vaccine efficacy.


Assuntos
Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/mortalidade , Acinetobacter baumannii/imunologia , Pneumonia Bacteriana/mortalidade , Pneumonia Bacteriana/patologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/isolamento & purificação , Animais , Carga Bacteriana/imunologia , Vacinas Bacterianas/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Citometria de Fluxo , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Pneumonia Bacteriana/microbiologia , RNA Mensageiro/biossíntese , Vacinação
14.
Artigo em Inglês | MEDLINE | ID: mdl-30131944

RESUMO

Multidrug efflux systems contribute to antimicrobial resistance and pathogenicity in bacteria. Here, we report the identification and characterization of a transcriptional regulator AcrR controlling the yet uncharacterized multidrug efflux pump, AcrAB in Acinetobacter nosocomialis. In silico analysis revealed that the homologs of AcrR and AcrAB are reported in the genomes of many other bacterial species. We confirmed that the genes encoding the AcrAB efflux pump, acrA and acrB forms a polycistronic operon which is under the control of acrR gene upstream of acrA. Bioinformatic analysis indicated the presence of AcrR binding motif in the promoter region of acrAB operon and the specific binding of AcrR was confirmed by electrophoretic mobility shift assay (EMSA). The EMSA data showed that AcrR binds to -89 bp upstream of the start codon of acrA. The mRNA expression analysis depicted that the expression of acrA and acrB genes are elevated in the deletion mutant compared to that in the wild type confirming that AcrR acts as a repressor of acrAB operon in A. nosocomialis. The deletion of acrR resulted in increased motility, biofilm/pellicle formation and invasion in A. nosocomialis. We further analyzed the role of AcrR in A. nosocomialis pathogenesis in vivo using murine model and it was shown that acrR mutant is highly virulent inducing severe infection in mouse leading to host death. In addition, the intracellular survival rate of acrR mutant was higher compared to that of wild type. Our data demonstrates that AcrR functions as an important regulator of AcrAB efflux pump and is associated with several phenotypes such as motility, biofilm/pellicle formation and pathogenesis in A. nosocomialis.


Assuntos
Acinetobacter/crescimento & desenvolvimento , Acinetobacter/genética , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Repressoras/metabolismo , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Animais , Sítios de Ligação , Biologia Computacional , DNA Bacteriano/metabolismo , Modelos Animais de Doenças , Ensaio de Desvio de Mobilidade Eletroforética , Proteínas de Membrana Transportadoras/genética , Camundongos , Óperon , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Repressoras/genética , Análise de Sobrevida , Virulência
15.
Mol Microbiol ; 109(6): 745-762, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29884996

RESUMO

Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi-drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon-sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc-GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract.


Assuntos
Infecções por Acinetobacter/patologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/patogenicidade , Membrana Celular/metabolismo , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas do Sistema Complemento/imunologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Camundongos , Camundongos Endogâmicos CBA , Ácidos Murâmicos/metabolismo , Peptidoglicano/metabolismo , Estresse Fisiológico
16.
Sci Rep ; 8(1): 7289, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29740176

RESUMO

The effect of biofilm formation on bacteraemic pneumonia caused by A. baumannii is unknown. We conducted a 4-year multi-center retrospective study to analyze 71 and 202 patients with A. baumannii bacteraemic pneumonia caused by biofilm-forming and non-biofilm-forming isolates, respectively. The clinical features and outcomes of patients were investigated. Biofilm formation was determined by a microtitre plate assay. The antimicrobial susceptibilities of biofilm-associated cells were assessed using the minimum biofilm eradication concentration (MBEC) assay. Whole-genome sequencing was conducted to identify biofilm-associated genes and their promoters. Quantitative reverse transcription polymerase chain reaction was performed to confirm the expression difference of biofilm-associated genes. There was no significant difference in the clinical characteristics or the outcomes between patients infected with biofilm-forming and non-biofilm-forming strains. Compared with non-biofilm-forming isolates, biofilm-forming isolates exhibited lower resistance to most antimicrobials tested, including imipenem, meropenem, ceftazidime, ciprofloxacin and gentamicin; however, the MBEC assay confirmed the increased antibiotic resistance of the biofilm-embedded bacteria. Biofilm-associated genes and their promoters were detected in most isolates, including the non-biofilm-forming strains. Biofilm-forming isolates showed higher levels of expression of the biofilm-associated genes than non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii isolates might not be associated with worse outcomes in patients with bacteraemic pneumonia.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Infecções por Acinetobacter/genética , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Acinetobacter baumannii/patogenicidade , Antibacterianos/administração & dosagem , Biofilmes/crescimento & desenvolvimento , Ciprofloxacino/administração & dosagem , Farmacorresistência Bacteriana Múltipla , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Meropeném/administração & dosagem , Testes de Sensibilidade Microbiana , Pneumonia/genética , Pneumonia/microbiologia , Pneumonia/patologia , Estudos Retrospectivos
17.
PLoS Pathog ; 14(5): e1007030, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29795704

RESUMO

The nosocomial pathogen Acinetobacter baumannii is a significant threat due to its ability to cause infections refractory to a broad range of antibiotic treatments. We show here that a highly conserved sensory-transduction system, BfmRS, mediates the coordinate development of both enhanced virulence and resistance in this microorganism. Hyperactive alleles of BfmRS conferred increased protection from serum complement killing and allowed lethal systemic disease in mice. BfmRS also augmented resistance and tolerance against an expansive set of antibiotics, including dramatic protection from ß-lactam toxicity. Through transcriptome profiling, we showed that BfmRS governs these phenotypes through global transcriptional regulation of a post-exponential-phase-like program of gene expression, a key feature of which is modulation of envelope biogenesis and defense pathways. BfmRS activity defended against cell-wall lesions through both ß-lactamase-dependent and -independent mechanisms, with the latter being connected to control of lytic transglycosylase production and proper coordination of morphogenesis and division. In addition, hypersensitivity of bfmRS knockouts could be suppressed by unlinked mutations restoring a short, rod cell morphology, indicating that regulation of drug resistance, pathogenicity, and envelope morphogenesis are intimately linked by this central regulatory system in A. baumannii. This work demonstrates that BfmRS controls a global regulatory network coupling cellular physiology to the ability to cause invasive, drug-resistant infections.


Assuntos
Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Farmacorresistência Bacteriana/genética , Infecções por Acinetobacter/patologia , Alelos , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana/imunologia , Farmacorresistência Bacteriana/fisiologia , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Regulação Bacteriana da Expressão Gênica/genética , Regulação Bacteriana da Expressão Gênica/imunologia , Homeostase/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/genética , Transcriptoma/imunologia , Virulência/efeitos dos fármacos , Virulência/imunologia , Resistência beta-Lactâmica/genética , beta-Lactamases/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-29844039

RESUMO

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggest that once-daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI). In a multicenter retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) of ≥30 ml/min who received ≥48 h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once- and twice-daily PMB dosing. The secondary endpoints included the time to AKI and the recovery of renal function. Of 273 eligible patients, 100 from each group were matched on the basis of propensity scores. In the matched groups, nephrotoxicity, defined according to risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria, was more frequent with once- than with twice-daily dosing (47% versus 17%, respectively; P = 0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once-daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio, 2.5; 95% confidence interval [CI], 1.413 to 4.541; P = 0.002). Among 64 patients who developed AKI, the median onsets were similar between the groups (7 days with once versus 6 days with twice-daily dosing, P = 0.095). Of 37 patients who had their serum creatinine evaluated subsequently, 29/37 (78%) had recovery of renal function. No patient required renal replacement therapy. Our findings suggest that AKI is significantly more common with PMB once daily than with twice-daily dosing with no difference in time to AKI. A prospective randomized study is warranted to validate these results.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Lesão Renal Aguda/diagnóstico , Antibacterianos/efeitos adversos , Falência Renal Crônica/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Polimixina B/efeitos adversos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/patogenicidade , Lesão Renal Aguda/sangue , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Idoso , Antibacterianos/sangue , Antibacterianos/farmacocinética , Creatinina/sangue , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Injeções Intravenosas , Falência Renal Crônica/sangue , Falência Renal Crônica/induzido quimicamente , Falência Renal Crônica/patologia , Testes de Função Renal , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/patogenicidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimixina B/sangue , Polimixina B/farmacocinética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade , Estudos Retrospectivos
19.
BMC Infect Dis ; 18(1): 159, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29614963

RESUMO

BACKGROUND: We describe the prevalence of invasive carbapenem-resistant Acinetobacter spp. isolated from 2005 to 2016 in different regions of Switzerland. METHODS: Using the Swiss Antibiotic Resistance Centre (anresis) database that includes data from 70% of all hospitalized patients and one third of all ambulatory practitioners in Switzerland, we analysed the number of carbapenem-susceptible and resistant Acinetobacter spp. isolated from blood or cerebrospinal fluid, and further described their temporal and regional fluctuations. RESULTS: From 2005 to 2016, 58 cases of resistant or intermediate strains to carbapenem were observed among 632 cases of invasive Acinetobacter. Multivariable analyses indicated that the number of carbapenem-resistant isolates (mean 4.8 ± sd 2.12) and carbapenem resistance rates per region per annum (8.4% ± 13.9%) were low and stable over the studied period. Large fluctuations were observed at the regional level, with e.g. the North East region displaying resistance rates twice as high as that found in other regions. CONCLUSION: Despite a relatively stable number of carbapenem-resistant Acinetobacter isolates in Switzerland, our results suggest the existence of a diverse pool of A. baumannii species in hospital settings, and confirm the implication of carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) complex in the vast majority of clinical infections and nosocomial outbreaks with notable regional fluctuations.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Bases de Dados Factuais , Farmacorresistência Bacteriana , Humanos , Prevalência , Suíça/epidemiologia
20.
Biomed Environ Sci ; 31(2): 155-158, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29606195

RESUMO

Acinetobacter baumannii (A. Baumannii) is an emerging opportunistic pathogen responsible for hospital-acquired infections, and which now constitutes a sufficiently serious threat to public health to necessitate the development of an effective vaccine. In this study, a recombinant fused protein named OmpK/Omp22 and two individual proteins OmpK and Omp22 were obtained using recombinant expression and Ni-affinity purification. Groups of BALB/c mice were immunized with these proteins and challenged with a clinically isolated strain of A. baumannii. The bacterial load in the blood, pathological changes in the lung tissue and survival rates after challenge were evaluated. Mice immunized with OmpK/Omp22 fused protein provided significantly greater protection against A. baumannii challenge than those immunized with either of the two proteins individually. The results provide novel clues for future design of vaccines against A. baumannii.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Pneumonia Bacteriana/prevenção & controle , Proteínas Recombinantes de Fusão/imunologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/genética , Animais , Anticorpos Antibacterianos/sangue , Carga Bacteriana , Proteínas da Membrana Bacteriana Externa/genética , Modelos Animais de Doenças , Feminino , Camundongos Endogâmicos BALB C , Pneumonia Bacteriana/patologia , Proteínas Recombinantes de Fusão/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA