Assuntos
Achromobacter denitrificans , Antibacterianos , Infecções por Bactérias Gram-Negativas , Humanos , Achromobacter denitrificans/efeitos dos fármacos , Achromobacter denitrificans/genética , Achromobacter denitrificans/isolamento & purificação , Antibacterianos/uso terapêutico , Evolução Molecular , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Leucemia/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE AND DESIGN: Our research aimed to investigate the role of CD14 in pulmonary infection by Achromobacter xylosoxidans in an experimental murine model. METHODS: C57Bl/6 or CD14-deficient mice were infected intratracheally with non-lethal inoculum of A. xylosoxidans. At times 1, 3 and 7 days after infection, lungs, bronchoalveolar lavage and blood were collected. CD14 gene expression was determined by RT-PCR. The bacterial load in the lungs was assessed by counting colony forming units (CFU). Cytokines, chemokines, lipocalin-2 and sCD14 were quantified by the ELISA method. Inflammatory infiltrate was observed on histological sections stained with HE, and leukocyte subtypes were assessed by flow cytometry. In another set of experiments, C57Bl/6 or CD14-deficient mice were inoculated with lethal inoculum and the survival rate determined. RESULTS: CD14-deficient mice are protected from A. xylosoxidans-induced death, which is unrelated to bacterial load. The lungs of CD14-deficient mice presented a smaller area of tissue damage, less neutrophil and macrophage infiltration, less pulmonary edema, and a lower concentration of IL-6, TNF-α, CXCL1, CCL2 and CCL3 when compared with lungs of C57Bl/6 mice. We also observed that A. xylosoxidans infection increases the number of leukocytes expressing mCD14 and the levels of sCD14 in BALF and serum of C57Bl/6-infected mice. CONCLUSIONS: In summary, our data show that in A. xylosoxidans infection, the activation of CD14 induces intense pulmonary inflammatory response resulting in mice death.
Assuntos
Achromobacter denitrificans , Infecções por Bactérias Gram-Negativas , Receptores de Lipopolissacarídeos , Pneumonia , Animais , Camundongos , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo , Infecções por Bactérias Gram-Negativas/metabolismoRESUMO
Introduction: Hyperimmunoglobulin E syndromes (HIESs) are characterized by a high serum immunoglobulin E (IgE) level, eczematoid rashes, recurrent staphylococcal skin abscesses, and recurrent pneumonia and pneumatocele formation. Autosomal dominant HIES is the most common form of HIES and mainly occurs due to loss-of-function mutations in the Signal Transducer and Activator of Transcription 3 (STAT3) gene (STAT3 LOF). Case Presentation: We report the case of an 11-year-old Peruvian girl diagnosed with STAT3 LOF caused by p.R382W mutation. She presented with recurrent staphylococcal pneumonia and empyema caused by the rarely reported Achromobacter xylosoxidans, which led to severe destruction of the lung parenchyma, multiple lung surgeries, and the development of bronchopleural fistulas. A laparotomy was also performed, which showed evidence of sigmoid colon perforation. The patient received immunoglobulin replacement therapy (IRT) and antibiotic prophylaxis, and the frequency of her infections has decreased over the past 3 years. Conclusion: This is the first case of STAT3 LOF diagnosed by genomic sequencing in Peru. Patients with this mutation have recurrent pulmonary infections, and require multiple surgical procedures with frequent complications. A. xylosoxidans infection could be related to the prolonged stay in intensive care leading to high mortality; therefore, additional care must be taken when treating patients with this infection. In addition, colonic perforation is a rare complication in STAT3 LOF patients. IRT and antibiotic prophylaxis appear to decrease the frequency of infections and hospitalizations.
Assuntos
Achromobacter denitrificans/isolamento & purificação , Empiema/microbiologia , Síndrome de Job/diagnóstico , Síndrome de Job/genética , Mutação com Perda de Função , Pneumonia Estafilocócica/cirurgia , Fator de Transcrição STAT3/genética , Criança , Empiema/diagnóstico , Humanos , Imunoglobulina E/genética , Masculino , Mutação , Pneumonia Estafilocócica/microbiologia , Complicações Cognitivas Pós-Operatórias , Análise de Sequência de DNARESUMO
BACKGROUND: Hospital reservoirs of Achromobacter xylosoxidans, responsible for nosocomial infections, are poorly known. METHODS: We examined the growth, survival and biofilm formation of five A. xylosoxidans strains for up to 2 y in distilled, dialysis or microfiltered water. Each strain was inoculated at 102 CFU/ml without adding nutrients. RESULTS: All strains grew at a level of 3x103 to 1.5x107 CFU/ml; each strain showed a preferred water type. Strains isolated from quaternary ammoniums showed the highest ability to grow and form biofilms in nutrient-poor waters. CONCLUSION: Medical waters and notably sterile distilled water bottles appear to be long-lasting reservoirs of A. xylosoxidans.
Assuntos
Achromobacter denitrificans , Biofilmes , Hospitais , HumanosRESUMO
BACKGROUND: Achromobacter xylosoxidans is described as being resistant to antiseptics and disinfectants. We studied in vitro the ability of five strains to survive and grow in such solutions, with and without starvation. METHODS: Bacterial suspensions in rich media and in distilled water were inoculated into eight antiseptics or disinfectants under conditions of use. RESULTS: All strains from cultures in distilled water survived in aqueous chlorhexidine and only environmental strains survived in a quaternary ammonium-based disinfectant. Survival did not exceed 30 min and no growth was observed. CONCLUSIONS: This study highlights a relationship between starvation and survival in antiseptics and disinfectants.
Assuntos
Achromobacter denitrificans/efeitos dos fármacos , Anti-Infecciosos Locais/farmacologia , Desinfetantes/farmacologia , Testes de Sensibilidade MicrobianaAssuntos
Achromobacter denitrificans/isolamento & purificação , Bacteriemia/diagnóstico , Complicações do Diabetes/diagnóstico , Infecções por Bactérias Gram-Negativas/diagnóstico , Abscesso Hepático/diagnóstico , Cirrose Hepática/complicações , Bacteriemia/etiologia , Complicações do Diabetes/etiologia , Evolução Fatal , Infecções por Bactérias Gram-Negativas/etiologia , Humanos , Abscesso Hepático/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
We describe the genome sequence of Pseudomonas reinekei MT1 and Achromobacter xylosoxidans MT3, the most abundant members of a bacterial community capable of degrading chloroaromatic compounds. The MT1 genome contains open reading frames encoding enzymes responsible for the catabolism of chlorosalicylate, methylsalicylate, chlorophenols, phenol, benzoate, p-coumarate, phenylalanine, and phenylacetate. On the other hand, the MT3 strain genome possesses no ORFs to metabolize chlorosalicylates; instead the bacterium is capable of metabolizing nitro-phenolic and phenolic compounds, which can be used as the only carbon and energy source by MT3. We also confirmed that MT3 displays the genetic machinery for the metabolism of chlorocathecols and chloromuconates, where the latter are toxic compounds secreted by MT1 when degrading chlorosalicylates. Altogether, this work will advance our fundamental understanding of bacterial interactions.
Assuntos
Achromobacter denitrificans/genética , Pseudomonas/genética , Análise de Sequência de DNA/métodos , Composição de Bases , Vias Biossintéticas , Mapeamento Cromossômico , Tamanho do Genoma , Genoma Bacteriano , Filogenia , Pseudomonas/classificaçãoAssuntos
Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Bactérias Gram-Negativas/diagnóstico , Bacteriemia/diagnóstico , Achromobacter denitrificans/isolamento & purificação , Complicações do Diabetes/diagnóstico , Abscesso Hepático/diagnóstico , Cirrose Hepática/complicações , Infecções por Bactérias Gram-Negativas/etiologia , Bacteriemia/etiologia , Evolução Fatal , Complicações do Diabetes/etiologia , Abscesso Hepático/complicaçõesRESUMO
Leukotriene B4 (LTB4) is essential for host immune defence. It increases neutrophil recruitment, phagocytosis and pathogen clearance, and decreases oedema and inflammasome activation. The host response and the role of LTB4 during Achromobacter xylosoxidans infection remain unexplored. Wild-type (129sv) and LTB4 deficient (Alox5 -/-) mice were intratracheally infected with A. xylosoxidans. Wild-type 129sv infected mice survived beyond the 8th day post-infection, exhibited increased levels of LTB4 in the lung on the 1st day, while levels of PGE2 increased on the 7th day post-infection. Infected Alox5 -/- mice showed impaired bacterial clearance, increased lung inflammation, and succumbed to the infection by the 7th day. We found that exogenous LTB4 does not affect the phagocytosis of A. xylosoxidans by alveolar macrophages in vitro. However, treatment of infected animals with LTB4 protected from mortality, by reducing the bacterial load and inflammation via BLT1 signalling, the high affinity receptor for LTB4. Of importance, we uncovered that LTB4 induces gene and protein expression of α-defensin-1 during the infection. This molecule is essential for bacterial clearance and exhibits potent antimicrobial activity by disrupting A. xylosoxidans cell wall. Taken together, our data demonstrate a major role for LTB4 on the control of A. xylosoxidans infection.