RESUMEN
Following pilus-mediated adhesion to human brain endothelial cells, meningococcus (N. meningitidis), the bacterium causing cerebrospinal meningitis, initiates signaling cascades, which eventually result in the opening of intercellular junctions, allowing meningeal colonization. The signaling receptor activated by the pathogen remained unknown. We report that N. meningitidis specifically stimulates a biased ß2-adrenoceptor/ß-arrestin signaling pathway in endothelial cells, which ultimately traps ß-arrestin-interacting partners, such as the Src tyrosine kinase and junctional proteins, under bacterial colonies. Cytoskeletal reorganization mediated by ß-arrestin-activated Src stabilizes bacterial adhesion to endothelial cells, whereas ß-arrestin-dependent delocalization of junctional proteins results in anatomical gaps used by bacteria to penetrate into tissues. Activation of ß-adrenoceptor endocytosis with specific agonists prevents signaling events downstream of N. meningitidis adhesion and inhibits bacterial crossing of the endothelial barrier. The identification of the mechanism used for hijacking host cell signaling machineries opens perspectives for treatment and prevention of meningococcal infection.
Asunto(s)
Arrestinas/metabolismo , Encéfalo/microbiología , Células Endoteliales/microbiología , Infecciones Meningocócicas/metabolismo , Neisseria meningitidis/metabolismo , Receptores Adrenérgicos beta/metabolismo , Transducción de Señal , Adhesión Bacteriana , Barrera Hematoencefálica , Línea Celular , Humanos , Infecciones Meningocócicas/microbiología , beta-ArrestinasRESUMEN
The efficient natural transformation of Neisseria meningitidis allows the rapid construction of bacterial mutants in which the genes of interest are interrupted or replaced by antibiotic-resistance cassettes. However, this proved to be a double-edged sword, i.e., although facilitating the genetic characterization of this important human pathogen, it has limited the development of strategies for constructing markerless mutants without antibiotic-resistance markers. In addition, efficient tools for complementation or labeling are also lacking in N. meningitidis. In this study, we significantly expand the meningococcal genetic toolbox by developing new and efficient tools for the construction of markerless mutants (using a dual counterselection strategy), genetic complementation (using integrative vectors), and cell labeling (using a self-labeling protein tag). This expanded toolbox paves the way for more in-depth genetic characterization of N. meningitidis and might also be useful in other Neisseria species.IMPORTANCENeisseria meningitidis and Neisseria gonorrhoeae are two important human pathogens. Research focusing on these bacteria requires genetic engineering, which is facilitated by their natural ability to undergo transformation. However, the ease of mutant engineering has led the Neisseria community to neglect the development of more sophisticated tools for gene editing, particularly for N. meningitidis. In this study, we have significantly expanded the meningococcal genetic toolbox by developing novel and efficient tools for markerless mutant construction, genetic complementation, and cell tagging. This expanded toolbox paves the way for more in-depth genetic characterization of N. meningitidis and might also be useful in other Neisseria species.
RESUMEN
Helicobacter cinaedi bacteremia caused recurring multifocal cellulitis in a patient in France who had chronic lymphocytic leukemia treated with ibrutinib. Diagnosis required extended blood culture incubation and sequencing of the entire 16S ribosomal RNA gene from single bacterial colonies. Clinicians should consider H. cinaedi infection in cases of recurrent cellulitis.
Asunto(s)
Bacteriemia , Infecciones por Helicobacter , Helicobacter , Humanos , Celulitis (Flemón)/diagnóstico , Celulitis (Flemón)/microbiología , Helicobacter/genética , Bacteriemia/microbiología , Infecciones por Helicobacter/diagnósticoRESUMEN
Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFNâº) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Interferón-alfa/efectos adversos , Infecciones Fúngicas Invasoras/etiología , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Zidovudina/efectos adversos , Adolescente , Adulto , Anciano , Profilaxis Antibiótica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aspergilosis/epidemiología , Aspergilosis/etiología , Neutropenia Febril/complicaciones , Femenino , Fiebre de Origen Desconocido/epidemiología , Fiebre de Origen Desconocido/etiología , Fungemia/epidemiología , Fungemia/etiología , Humanos , Interferón-alfa/administración & dosificación , Infecciones Fúngicas Invasoras/epidemiología , Estimación de Kaplan-Meier , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/mortalidad , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/etiología , Neumonía por Pneumocystis/epidemiología , Neumonía por Pneumocystis/etiología , Prevalencia , Pronóstico , Estudios Retrospectivos , Estrongiloidiasis/epidemiología , Estrongiloidiasis/etiología , Estrongiloidiasis/prevención & control , Resultado del Tratamiento , Adulto Joven , Zidovudina/administración & dosificaciónRESUMEN
Purpura fulminans is a deadly complication of Neisseria meningitidis infections due to extensive thrombosis of microvessels. Although a Disseminated Intra-vascular Coagulation syndrome (DIC) is frequently observed during Gram negative sepsis, it is rarely associated with extensive thrombosis like those observed during meningococcemia, suggesting that the meningococcus induces a specific dysregulation of coagulation. Another specific feature of N. meningitidis pathogenesis is its ability to colonize microvessels endothelial cells via type IV pili. Importantly, endothelial cells are key in controlling the coagulation cascade through the activation of the potent anticoagulant Protein C (PC) thanks to two endothelial cell receptors among which the Endothelial Protein C Receptor (EPCR). Considering that congenital or acquired deficiencies of PC are associated with purpura fulminans, we hypothesized that a defect in the activation of PC following meningococcal adhesion to microvessels is responsible for the thrombotic events observed during meningococcemia. Here we showed that the adhesion of N. meningitidis on endothelial cells results in a rapid and intense decrease of EPCR expression by inducing its cleavage in a process know as shedding. Using siRNA experiments and CRISPR/Cas9 genome edition we identified ADAM10 (A Disintegrin And Metalloproteinase-10) as the protease responsible for this shedding. Surprisingly, ADAM17, the only EPCR sheddase described so far, was not involved in this process. Finally, we showed that this ADAM10-mediated shedding of EPCR induced by the meningococcal interaction with endothelial cells was responsible for an impaired activation of Protein C. This work unveils for the first time a direct link between meningococcal adhesion to endothelial cells and a severe dysregulation of coagulation, and potentially identifies new therapeutic targets for meningococcal purpura fulminans.
Asunto(s)
Proteína ADAM10/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Receptor de Proteína C Endotelial/metabolismo , Endotelio Vascular/patología , Proteínas de la Membrana/metabolismo , Infecciones Meningocócicas/complicaciones , Microvasos/patología , Proteína C/metabolismo , Púrpura Fulminante/etiología , Proteína ADAM10/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Adhesión Bacteriana , Coagulación Sanguínea/fisiología , Células Cultivadas , Receptor de Proteína C Endotelial/genética , Endotelio Vascular/metabolismo , Endotelio Vascular/microbiología , Humanos , Proteínas de la Membrana/genética , Infecciones Meningocócicas/microbiología , Microvasos/metabolismo , Microvasos/microbiología , Neisseria meningitidis/fisiología , Proteína C/genética , Púrpura Fulminante/metabolismo , Púrpura Fulminante/patologíaRESUMEN
Neisseria meningitidis is a Gram-negative bacterium that asymptomatically colonises the nasopharynx of humans. For an unknown reason, N. meningitidis can cross the nasopharyngeal barrier and invade the bloodstream where it becomes one of the most harmful extracellular bacterial pathogen. This infectious cycle involves the colonisation of two different environments. (a) In the nasopharynx, N. meningitidis grow on the top of mucus-producing epithelial cells surrounded by a complex microbiota. To survive and grow in this challenging environment, the meningococcus expresses specific virulence factors such as polymorphic toxins and MDAΦ. (b) Meningococci have the ability to survive in the extra cellular fluids including blood and cerebrospinal fluid. The interaction of N. meningitidis with human endothelial cells leads to the formation of typical microcolonies that extend overtime and promote vascular injury, disseminated intravascular coagulation, and acute inflammation. In this review, we will focus on the interplay between N. meningitidis and these two different niches at the cellular and molecular level and discuss the use of inhibitors of piliation as a potent therapeutic approach.
Asunto(s)
Infecciones Meningocócicas/microbiología , Nasofaringe/microbiología , Neisseria meningitidis/patogenicidad , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Vasos Sanguíneos/microbiología , Células Endoteliales/patología , Células Epiteliales/patología , Interacciones Microbiota-Huesped , Humanos , Inovirus/crecimiento & desarrollo , Inovirus/patogenicidad , Infecciones Meningocócicas/sangre , Infecciones Meningocócicas/líquido cefalorraquídeo , Neisseria meningitidis/metabolismo , Factores de VirulenciaRESUMEN
We report a disseminated infection caused by Spiroplasma apis, a honeybee pathogen, in a patient in France who had X-linked agammaglobulinemia. Identification was challenging because initial bacterial cultures and direct examination by Gram staining were negative. Unexplained sepsis in patients with agammaglobulinemia warrants specific investigation to identify fastidious bacteria such as Spiroplasma spp.
Asunto(s)
Agammaglobulinemia/complicaciones , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/etiología , Spiroplasma , Adulto , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/terapia , Antibacterianos/uso terapéutico , Biopsia , Francia , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , ARN Ribosómico 16S/metabolismo , Piel/microbiología , Piel/patología , Spiroplasma/clasificación , Spiroplasma/genética , Resultado del TratamientoRESUMEN
Bacteraemia was reported to be associated with false-positive 1â3-ß-D-glucan (BG) assay results. We thus prospectively assessed the reactivity of the BG (Fungitell) in samples of 21 adults with bacteraemia: . BG was negative in all and is s therefore an unlikely cause of false positive BG in adults.
Asunto(s)
Bacteriemia/patología , beta-Glucanos/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Proteoglicanos , Suero/química , Adulto JovenRESUMEN
BACKGROUND: Few data exist on the efficacy of combined antiretroviral therapy (cART) in semen of human immunodeficiency virus type 1 (HIV-1) infected men who have sex with men (MSM) with sustained control of HIV replication in blood. METHODS: HIV-1 infected MSM on successful cART for >6 months were enrolled. HIV-RNA was quantified in seminal plasma (spVL) and in blood plasma (bpVL) from 2 paired samples collected 4 weeks apart. Relationship between spVL and bpVL (measured by an ultrasensitive assay, LOQ 10 copies/mL), total peripheral blood mononuclear cells (PBMC)-associated HIV-DNA, sexually transmitted infections (STIs), and self-reported socio-behavioral characteristics was assessed using GEE logistic regression. RESULTS: In total, 157 patients were included. Median time with bpVL <50 copies/mL was 3.3 years. spVL was detectable in 23/304 samples (prevalence 7.6%). Median spVL was 145 cp/mL (100-1475). spVL was detectable on the first, on the second, and on both samples in 5, 14, and 2 men, respectively. In sum, 33 individuals (21%) had STIs (asymptomatic in 24/33). Residual bpVL was undetectable by ultrasensitive assay in 225/300 samples (75%). After multivariable adjustments, PBMC-associated HIV-DNA (OR 2.6[1.2; 6.0], for HIV-DNA > 2.5 log10 cp/10(6) PBMC, P = .02), and cannabis use during sexual intercourse (OR 2.8[1.2; 6.7], P = .02) were the only factors associated significantly with spVL. CONCLUSION: We show that HIV-RNA can be detected intermittently in semen of HIV-1 infected MSM despite successful cART. The size of blood HIV-1 reservoir predicted spVL detection. Our results indicated also that the possible effect of cannabis should be taken into account when developing prevention interventions targeted toward HIV-infected MSM on successful cART.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , ADN Viral/análisis , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Homosexualidad Masculina , Semen/virología , Adulto , Quimioterapia Combinada , VIH-1/genética , Humanos , Leucocitos Mononucleares/química , Masculino , Fumar Marihuana , Persona de Mediana Edad , ARN Viral/análisis , Semen/química , Enfermedades Bacterianas de Transmisión Sexual/diagnóstico , Carga Viral , Esparcimiento de VirusRESUMEN
The brain and meningeal spaces are protected from bacterial invasion by the blood-brain barrier, formed by specialized endothelial cells and tight intercellular junctional complexes. However, once in the bloodstream, Neisseria meningitidis crosses this barrier in about 60% of the cases. This highlights the particular efficacy with which N. meningitidis targets the brain vascular cell wall. The first step of central nervous system invasion is the direct interaction between bacteria and endothelial cells. This step is mediated by the type IV pili, which induce a remodelling of the endothelial monolayer, leading to the opening of the intercellular space. In this review, strategies used by the bacteria to survive in the bloodstream, to colonize the brain vasculature and to cross the blood-brain barrier will be discussed.
Asunto(s)
Barrera Hematoencefálica/microbiología , Encéfalo/microbiología , Líquido Cefalorraquídeo/microbiología , Endotelio/microbiología , Neisseria meningitidis/fisiología , Barrera Hematoencefálica/inmunología , Fimbrias Bacterianas/metabolismo , Interacciones Huésped-Patógeno , Neisseria meningitidis/crecimiento & desarrolloRESUMEN
Neisseria meningitidis is a strict human pathogen that closely interacts with human endothelial cells via type IV pili in vitro. To decipher whether this interaction plays a role in vivo, we set up an experimental model of fulminant meningococcemia in human skin grafted SCID mice using the wild-type strain 2C4.3. Human skin and mouse tissues were sampled 24 hours after bacterial challenge for histopathology, immunohistochemistry and ultrastructural analysis. In all infected mice, N. meningitidis targeted the human vasculature, leading to bacterial and blood thrombi, infectious vasculitis and vascular leakage. Mouse vessels, including brain vessels, remained unaffected by the infectious and thrombotic process, and a nonpiliated Δ pilE derivative of 2C4.3 failed to target human graft vessels and to induce vascular damages. These data demonstrate that N. meningitidis targets human endothelial cells in vivo and that this interaction triggers the vascular damages that characterize purpura fulminans.
Asunto(s)
Microvasos/microbiología , Neisseria meningitidis/fisiología , Púrpura Fulminante/etiología , Púrpura Fulminante/patología , Animales , Adhesión Bacteriana , Células Endoteliales/microbiología , Células Endoteliales/patología , Endotelio Vascular/microbiología , Endotelio Vascular/patología , Femenino , Fimbrias Bacterianas/fisiología , Xenoinjertos , Humanos , Infecciones Meningocócicas/complicaciones , Infecciones Meningocócicas/microbiología , Ratones , Microvasos/patología , Piel/irrigación sanguínea , Piel/patología , Trasplante de PielRESUMEN
BACKGROUND: Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described. RESEARCH QUESTION: What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients? STUDY DESIGN AND METHODS: In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU. RESULTS: One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022). INTERPRETATION: LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.
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Legionella pneumophila , Enfermedad de los Legionarios , Trasplante de Órganos , Humanos , Enfermedad de los Legionarios/diagnóstico , Enfermedad de los Legionarios/epidemiología , Enfermedad de los Legionarios/microbiología , Estudios Retrospectivos , Factores de Riesgo , Trasplante de Órganos/efectos adversosRESUMEN
Evaluating the clinical significance of blood cultures positive for coagulase-negative staphylococci (CoNS) is of critical importance since these microorganisms represent both the first contaminants of blood cultures and one of the leading causes of bloodstream infection (BSI). This prospective 2-centre study aimed to compare a previously reported algorithm to a clinical algorithm based on our experience. We identified 84 patients with CoNS-positive blood cultures. Twenty-seven (32%) were considered to have BSI according to our study algorithm. Thirty-seven (44%) patients were considered to have CoNS BSI according to the previously reported algorithm. The 2 algorithms isolated patients with similar rates of recurrences and hospital mortality. Our algorithm seemed to result in less diagnoses of CoNS BSI without harmful consequences compared to the previously reported algorithm. The impact on patient outcome and the inappropriate use of antibiotics deserves further investigation.
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Bacteriemia/diagnóstico , Técnicas Bacteriológicas/métodos , Sangre/microbiología , Medicina Clínica/métodos , Staphylococcus/aislamiento & purificación , Adulto , Anciano , Algoritmos , Bacteriemia/mortalidad , Coagulasa/deficiencia , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Análisis de Supervivencia , Adulto JovenRESUMEN
A 3-year-old male originating from Djibouti presented with a cervical mass evolving for 2 months. Tuberculous lymphadenopathy was suspected based on biopsy results, and he improved quickly on standard antituberculous quadritherapy. Subsequently some features of the mycobacterium that grew in culture were unusual. The isolate was eventually identified as Mycobacterium canettii , a peculiar species of the Mycobacterium tuberculosis complex.
Asunto(s)
Linfadenopatía , Mycobacterium tuberculosis , Mycobacterium , Tuberculosis Ganglionar , Masculino , Humanos , Preescolar , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Ganglionar/tratamiento farmacológico , DjiboutiRESUMEN
BACKGROUND: Worldwide, Escherichia coli is the leading cause of neonatal Gram-negative bacterial meningitis, but full understanding of the pathogenesis of this disease is not yet achieved. Moreover, to date, no vaccine is available against bacterial neonatal meningitis. METHODS: Here, we used Transposon Sequencing of saturated banks of mutants (TnSeq) to evaluate E. coli K1 genetic fitness in murine neonatal meningitis. We identified E. coli K1 genes encoding for factors important for systemic dissemination and brain infection, and focused on products with a likely outer-membrane or extra-cellular localization, as these are potential vaccine candidates. We used in vitro and in vivo models to study the efficacy of active and passive immunization. RESULTS: We selected for further study the conserved surface polysaccharide Poly-ß-(1-6)-N-Acetyl Glucosamine (PNAG), as a strong candidate for vaccine development. We found that PNAG was a virulence factor in our animal model. We showed that both passive and active immunization successfully prevented and/or treated meningitis caused by E. coli K1 in neonatal mice. We found an excellent opsonophagocytic killing activity of the antibodies to PNAG and in vitro these antibodies were also able to decrease binding, invasion and crossing of E. coli K1 through two blood brain barrier cell lines. Finally, to reinforce the potential of PNAG as a vaccine candidate in bacterial neonatal meningitis, we demonstrated that Group B Streptococcus, the main cause of neonatal meningitis in developed countries, also produced PNAG and that antibodies to PNAG could protect in vitro and in vivo against this major neonatal pathogen. INTERPRETATION: Altogether, these results indicate the utility of a high-throughput DNA sequencing method to identify potential immunotherapy targets for a pathogen, including in this study a potential broad-spectrum target for prevention of neonatal bacterial infections. FUNDINGS: ANR Seq-N-Vaq, Charles Hood Foundation, Hearst Foundation, and Groupe Pasteur Mutualité.
Asunto(s)
Escherichia coli , Meningitis Bacterianas , Animales , Ratones , Escherichia coli/genética , Anticuerpos Antibacterianos , Bacterias/genética , Inmunoterapia , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Following adhesion on brain microvasculature, Neisseria meningitidis is able to cross the blood-brain barrier (BBB) by recruiting the polarity complex and the cell junction proteins, thus allowing the opening of the paracellular route. This feature is the consequence of the activation by the type IV pili of the ß2-adrenergic receptor/ß-arrestin signaling pathway. Here, we have extended this observation to primary peripheral endothelial cells, and we report that the interaction of N. meningitidis with the epithelium is strikingly different. The recruitment of the junctional components by N. meningitidis is indeed restricted to endothelial cell lines, and no alteration of the cell-cell junctions can be seen in epithelial monolayers following meningococcal type IV pilus-mediated colonization. Consistently, the ß2-adrenergic receptor/ß-arrestin pathway was not hijacked by bacteria adhering on epithelial cells. In addition, we showed that the consequences of the bacterial signaling on epithelial cells is different from that of endothelial cells, since N. meningitidis-induced signaling which protects the microcolonies from shear stress on endothelial cells is unable to do so on epithelial cells. Finally, we report that the minor pilin PilV, which has been shown to be essential for endothelial cell response, is not a required bacterial determinant to induce an epithelial cell response. These data demonstrate that even though pilus-mediated signaling induces an apparently similar cortical plaque, in epithelial and endothelial cell lineages, the signaling pathways are strikingly different in both models.
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Adhesión Bacteriana , Células Endoteliales/microbiología , Células Epiteliales/microbiología , Fimbrias Bacterianas/metabolismo , Neisseria meningitidis/patogenicidad , Transducción de Señal , Factores de Virulencia/metabolismo , Células Cultivadas , Células Endoteliales/fisiología , Células Epiteliales/fisiología , Humanos , Uniones Intercelulares/fisiología , Neisseria meningitidis/metabolismoRESUMEN
Chronic meningococcemia is a form of sepsis with frequent polymorphous skin lesions. Both in vivo and in vitro data suggest that, in these lesions, meningococci gain access from the capillary lumen to the peripheral extravascular compartment, in the absence of vascular dislocation, through a paraendothelial route.
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Bacteriemia/patología , Infecciones Meningocócicas/patología , Enfermedades Cutáneas Bacterianas/patología , Bacteriemia/complicaciones , Enfermedad Crónica , Endotelio/microbiología , Endotelio/patología , Enfermedades Cutáneas Bacterianas/microbiologíaRESUMEN
Acinetobacter baumannii isolate AP was recovered from a bronchial lavage of a patient hospitalized in Paris, France. A. baumannii AP was resistant to all ß-lactams, including carbapenems, and produced the extended-spectrum ß-lactamase (ESBL) GES-14, which differs from GES-1 by two substitutions, Gly170Ser and Gly243Ala. Cloning of the bla(GES-14) gene followed by its expression in Escherichia coli showed that GES-14 compromised significantly the efficacy of all ß-lactams, including cephalosporins, aztreonam, and carbapenems. The carbapenemase activity of purified GES-14 was confirmed by kinetic studies. The bla(GES-14) gene was located into a class 1 integron structure and located onto a ca. 95-kb self-transferable plasmid. This study identified a very broad-spectrum ß-lactamase in A. baumannii.
Asunto(s)
Acinetobacter baumannii/enzimología , Carbapenémicos/metabolismo , beta-Lactamasas/metabolismo , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacología , Carbapenémicos/farmacología , Ácido Clavulánico/farmacología , Escherichia coli/genética , Escherichia coli/metabolismo , Pruebas de Sensibilidad Microbiana , Modelos Genéticos , Datos de Secuencia Molecular , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/farmacología , Reacción en Cadena de la Polimerasa , Tazobactam , beta-Lactamasas/genéticaRESUMEN
Acinetobacter baumannii isolate AP2 was recovered from a bronchial lavage sample of a patient hospitalized in Paris, France. A. baumannii AP2 was resistant to all ß-lactams, including carbapenems, and expressed the extended-spectrum ß-lactamase (ESBL) PER-7, which differs from PER-1 by 4 amino acid substitutions. Compared to PER-1, PER-7 possessed higher-level hydrolytic activities against cephalosporins and aztreonam. The blaPER-7 gene was chromosomally located and associated with a mosaic class 1 integron structure. Additionally, isolate AP2 expressed the carbapenem-hydrolyzing oxacillinase OXA-23 and the 16S RNA methylase ArmA, conferring high-level resistance to aminoglycosides.