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1.
Epidemiol Mikrobiol Imunol ; 70(1): 72-75, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33853341

RESUMEN

Acute abdominal clinical presentations as initial manifestation of meningococcal infection are uncommon and frequently provoked by hyperinvasive isolates of meningococci. 10% of patients infected by the meningococcal strain, that is on the rise in Europe, suffer from abdominal pain. We hereby report the first laboratory confirmed fatal case of an otherwise healthy adult male presented with acute abdominal pain during first 24-48 hours, masking Neisseria meningitidis (N. meningitidis) infection. In the National Reference Center for meningococci, in the blood of a man post-mortem, we identified N. meningitidis serogroup C using real time polymerase chain reaction (PCR). Subsequently, massivelly-parallel sequencing (MPS) was performed on isolated total DNA for pathogen confirmation and further investigation.


Asunto(s)
Infecciones Meningocócicas , Neisseria meningitidis , Adulto , Europa (Continente) , Humanos , Laboratorios , Masculino , Infecciones Meningocócicas/diagnóstico , Serogrupo , Eslovaquia/epidemiología
3.
J Med Microbiol ; 70(3)2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33544069

RESUMEN

Invasive meningococcal disease (IMD) is a major cause of meningitis and septicaemia worldwide. The switches in serogroup predominance contribute to the unpredictable nature of the disease with significant health impacts. The aim of this study was to determine the epidemiological profile of IMD in Rio Grande do Sul, Santa Catarina and Paraná, three states in the south of Brazil. All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2015 and 2019 were analysed. Proportions of serogroup and incidence by age were calculated. A total of 17 894 cases of IMD were reported during this period. Of these, 9029 cases (50 %) were due to serogroup C. Furthermore, serogroup W was responsible for almost half of the cases among children younger than 5 years old during 2017 and 2018, with an overall incidence of 33.3 cases per 100 000 infants. Despite the reduction in serogroup C after the introduction of meningococcal C conjugate vaccine into a childhood immunization programme in Brazil, it remains a significant healthcare issue in the south of the country. Changes in disease epidemiology were observed and serogroup W was the most common among children below 5 years of age in 2017 and 2018. Although future cost-effectiveness studies are necessary, our results could have future implications for meningococcal vaccination programmes.


Asunto(s)
Programas de Inmunización/estadística & datos numéricos , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Distribución por Edad , Brasil/epidemiología , Monitoreo Epidemiológico , Inmunización , Programas de Inmunización/tendencias , Incidencia , Infecciones Meningocócicas/microbiología , Vacunas Meningococicas/administración & dosificación , Neisseria meningitidis/clasificación , Neisseria meningitidis/inmunología , Neisseria meningitidis/aislamiento & purificación , Serogrupo
4.
Nucleic Acids Res ; 49(5): e29, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33330940

RESUMEN

Optogenetic control of CRISPR-Cas9 systems has significantly improved our ability to perform genome perturbations in living cells with high precision in time and space. As new Cas orthologues with advantageous properties are rapidly being discovered and engineered, the need for straightforward strategies to control their activity via exogenous stimuli persists. The Cas9 from Neisseria meningitidis (Nme) is a particularly small and target-specific Cas9 orthologue, and thus of high interest for in vivo genome editing applications. Here, we report the first optogenetic tool to control NmeCas9 activity in mammalian cells via an engineered, light-dependent anti-CRISPR (Acr) protein. Building on our previous Acr engineering work, we created hybrids between the NmeCas9 inhibitor AcrIIC3 and the LOV2 blue light sensory domain from Avena sativa. Two AcrIIC3-LOV2 hybrids from our collection potently blocked NmeCas9 activity in the dark, while permitting robust genome editing at various endogenous loci upon blue light irradiation. Structural analysis revealed that, within these hybrids, the LOV2 domain is located in striking proximity to the Cas9 binding surface. Together, our work demonstrates optogenetic regulation of a type II-C CRISPR effector and might suggest a new route for the design of optogenetic Acrs.


Asunto(s)
Proteína 9 Asociada a CRISPR/antagonistas & inhibidores , Proteína 9 Asociada a CRISPR/química , Sistemas CRISPR-Cas , Edición Génica/métodos , Neisseria meningitidis/enzimología , Optogenética/métodos , Línea Celular , Células HEK293 , Humanos , Luz , Modelos Moleculares , Ingeniería de Proteínas , Proteínas/química , Proteínas/efectos de la radiación
5.
Washington, D.C.; PAHO; 2020-12-11.
en Español | PAHO-IRIS | ID: phr-53136

RESUMEN

La vigilancia pasiva por laboratorio de Streptococcus pneumoniae se realiza en los países de la Región de las Américas desde 1993 bajo la denominación de Sistema Regional de Vacunas (SIREVA), con el apoyo de la Organización Panamericana de la Salud. En 1997, los países de la Región propusieron introducir las pruebas de laboratorio para Haemophilus influenzae, y en el 2000, para Neisseria meningitidis. Así se amplió la vigilancia por laboratorio de las enfermedades bacterianas invasivas con los tres patógenos anteriores, esta vez bajo la denominación de SIREVA II. La red está compuesta por 19 laboratorios nacionales de referencia situados en varios países. Durante los últimos años se han ido incorporando nuevos ensayos, entre ellos pruebas de biología molecular, que facilitan la detección de estos patógenos en muestras biológicas. Los datos de la vigilancia por laboratorio de los países de la Región se recopilan y se presentan desde el 2005 en el Informe regional de SIREVA II. El objetivo principal de esta publicación es compartir información sobre la identificación de estos patógenos en la vigilancia pasiva por laboratorio que realizan los países durante un año calendario, dar seguimiento a la distribución de sus serotipos o serogrupos y correlacionarlos con los presentes en las vacunas disponibles. Esta publicación proporciona información actualizada sobre los aislamientos invasivos de Streptococcus pneumoniae, Haemophilus influenzae y Neisseria meningitidis de muestras biológicas recogidas durante el 2017 y realizadas en laboratorios de países de las Américas. Los datos de la vigilancia por laboratorio de este informe conservan el esquema de presentación que la red definió hace varios años, pues son necesarios para mantener informados a los programas de salud pública, al personal de laboratorio y a la comunidad científica, así como para facilitar información útil a las decisiones basadas en la evidencia. Estos datos pueden servir para promover estudios adicionales que generen nuevo conocimiento y faciliten la comprensión de estos eventos.


Asunto(s)
Enfermedades Transmisibles , Enfermedades Prevenibles por Vacunación , Farmacorresistencia Microbiana , Streptococcus pneumoniae , Haemophilus influenzae , Neisseria meningitidis , Infecciones Meningocócicas , Vacunas Meningococicas , Infecciones Neumocócicas , Vacunas Neumococicas
6.
Nat Commun ; 11(1): 5541, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33139723

RESUMEN

The bacterium Neisseria meningitidis causes life-threatening meningitis and sepsis. Here, we construct a complete collection of defined mutants in protein-coding genes of this organism, identifying all genes that are essential under laboratory conditions. The collection, named NeMeSys 2.0, consists of individual mutants in 1584 non-essential genes. We identify 391 essential genes, which are associated with basic functions such as expression and preservation of genome information, cell membrane structure and function, and metabolism. We use this collection to shed light on the functions of diverse genes, including a gene encoding a member of a previously unrecognised class of histidinol-phosphatases; a set of 20 genes required for type IV pili function; and several conditionally essential genes encoding antitoxins and/or immunity proteins. We expect that NeMeSys 2.0 will facilitate the phenotypic profiling of a major human bacterial pathogen.


Asunto(s)
Genes Bacterianos/genética , Genes Esenciales/genética , Mutación , Neisseria meningitidis/genética , Neisseria meningitidis/metabolismo , Fenotipo , Proteínas Bacterianas/metabolismo , Biología Computacional , Proteínas Fimbrias/genética , Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/metabolismo , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Humanos , Neisseria meningitidis/patogenicidad
7.
BMC Infect Dis ; 20(1): 733, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-33028262

RESUMEN

BACKGROUND: The morbidity and mortality in community-acquired bacterial meningitis (CABM) remain substantial, and the etiology, clinical characteristics, treatment outcomes and predictors of poor prognosis must be assessed regularly. The aim of this study was to identify the distribution of etiological agents and their relationship with clinical characteristics, treatment and outcomes in this cohort of patients with CABM. METHODS: Our retrospective chart review analyzed the causative microorganisms, clinical characteristics, laboratory findings, treatment and outcomes of 159 adults with CABM hospitalized in the Infectious Diseases Centre of Vilnius University Hospital from January 1, 2009 to December 31, 2016. A Glasgow Outcome Scale (GOS) score ≤ 3 was defined as unfavorable outcome. Predictors of an unfavorable outcome were identified through logistic regression analysis. RESULTS: The median patient age was 36 (IQR 24-56), and 51.6% were male. Microbiologically confirmed causative agents were identified in 80 (50.3%) patients: N. meningitidis in 55 (34.6%) patients with serotype B accounting for 85% of cases, S. pneumoniae in 15 (9.4%), L. monocytogenes in 5 (3.1%) and other in 5 (3.1%). The clinical triad of fever, neck stiffness and a change in mental status was present in 59.1% of patients. Coexisting conditions and comorbidities were similar in all groups stratified by etiology. Initial antimicrobial treatment consisted of penicillin in 78 patients (49.1%) and ceftriaxone in 72 patients (45.3%). The median time in which antibiotic treatment was started was 40 min (IQR 30.0-90.0). The outcome was unfavorable in 15.7% of episodes and death occurred in 5.7% of cases and did not differ according to the causative agent. Risk factors for an unfavorable outcome were age > 65 years, coexisting pneumonia and a platelet count <150x10e9/l. CONCLUSIONS: The most common causative agent of CABM was N. meningitidis, with serotype B clearly dominant. Causative agents did not influence the disease outcome. The strongest risk factors for an unfavorable outcome were older age, pneumonia and a low platelet count. Since the introduction of routine vaccination against meningococcus B for infants in Lithuania in 2018, the national vaccination policy may hopefully contribute to a decrease in the incidence of serogroup B meningococcal disease in the Lithuanian population.


Asunto(s)
Listeria monocytogenes/aislamiento & purificación , Meningitis Bacterianas/diagnóstico , Neisseria meningitidis/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Comorbilidad , Femenino , Humanos , Incidencia , Lituania , Masculino , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/microbiología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Serogrupo , Resultado del Tratamiento , Adulto Joven
8.
PLoS One ; 15(8): e0237883, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32866169

RESUMEN

Although whole-genome sequencing has provided novel insights into Neisseria meningitidis, many open reading frames have only been annotated as hypothetical proteins with unknown biological functions. Our previous genetic analyses revealed that the hypothetical protein, NMB1345, plays a crucial role in meningococcal infection in human brain microvascular endothelial cells; however, NMB1345 has no homology to any identified protein in databases and its physiological function could not be elucidated using pre-existing methods. Among the many biological technologies to examine transient protein-protein interaction in vivo, one of the developed methods is genetic code expansion with non-canonical amino acids (ncAAs) utilizing a pyrrolysyl-tRNA synthetase/tRNAPyl pair from Methanosarcina species: However, this method has never been applied to assign function-unknown proteins in pathogenic bacteria. In the present study, we developed a new method to genetically incorporate ncAAs-encoded photocrosslinking probes into N. meningitidis by utilizing a pyrrolysyl-tRNA synthetase/tRNAPyl pair and elucidated the biological function(s) of the NMB1345 protein. The results revealed that the NMB1345 protein directly interacts with PilE, a major component of meningococcal pili, and further physicochemical and genetic analyses showed that the interaction between the NMB1345 protein and PilE was important for both functional pilus formation and meningococcal infectious ability in N. meningitidis. The present study using this new methodology for N. meningitidis provides novel insights into meningococcal pathogenesis by assigning the function of a hypothetical protein.


Asunto(s)
Aminoácidos/genética , Reactivos de Enlaces Cruzados/metabolismo , Luz , Neisseria meningitidis/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Encéfalo/irrigación sanguínea , Endocitosis , Células Endoteliales/microbiología , Fimbrias Bacterianas/metabolismo , Humanos , Microvasos/patología , Mutación/genética , Plásmidos/genética
9.
J Vis Exp ; (161)2020 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-32744533

RESUMEN

Meningococcal meningitis is a life-threatening infection that occurs when Neisseria meningitidis (meningococcus, Nm) can gain access to the central nervous system (CNS) by penetrating highly specialized brain endothelial cells (BECs). As Nm is a human-specific pathogen, the lack of robust in vivo model systems makes study of the host-pathogen interactions between Nm and BECs challenging and establishes a need for a human based model that mimics native BECs. BECs possess tighter barrier properties when compared to peripheral endothelial cells characterized by complex tight junctions and elevated trans-endothelial electrical resistance (TEER). However, many in vitro models, such as primary BECs and immortalized BECs, either lack or rapidly lose their barrier properties after removal from the native neural microenvironment. Recent advances in human stem-cell technologies have developed methods for deriving brain-like endothelial cells from induced pluripotent stem-cells (iPSCs) that better phenocopy BECs when compared to other in vitro human models. The use of iPSC-derived BECs (iPSC-BECs) to model Nm-BEC interaction has the benefit of using human cells that possess BEC barrier properties, and can be used to examine barrier destruction, innate immune activation, and bacterial interaction. Here we demonstrate how to derive iPSC-BECs from iPSCs in addition to bacterial preparation, infection, and sample collection for analysis.


Asunto(s)
Encéfalo/citología , Células Endoteliales/citología , Células Endoteliales/microbiología , Células Madre Pluripotentes Inducidas/citología , Neisseria meningitidis/fisiología , Humanos
10.
Braz J Infect Dis ; 24(4): 349-351, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32659221

RESUMEN

The aim of this study was to compare the trajectory of serogroups causing Invasive Meningococcal Disease (IMD) in the Santa Catarina (SC) state with those of whole Brazil. A retrospective analysis of all IMD cases reported from January 2007 to December 2019 was carried out. During the study period, 26,058 IMD cases were registered in Brazil and 644 and in SC state alone. Overall, Brazil showed progressive reduction in cases since 2010, when the meningococcal C conjugate vaccine was introducted on National Immunization Program, while SC showed an increase in total cases since 2013, particularly from serogroups W and C. Serogroups distribution was significantly different between Brazil and SC. The emergence of serogroup W highlights the improved meningococcal surveillance through increased accuracy in identification methods in SC state. This finding is important for discussing recommendations of quadrivalent (ACWY) conjugate vaccines in different geographical areas of Brazil.


Asunto(s)
Infecciones Meningocócicas/epidemiología , Brasil/epidemiología , Humanos , Vacunas Meningococicas , Neisseria meningitidis , Estudios Retrospectivos , Serogrupo , Vacunas Conjugadas
11.
PLoS One ; 15(7): e0234475, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32663215

RESUMEN

BACKGROUND: Neisseria meningitidis is a significant cause of morbidity and mortality worldwide. Meningococcal isolates have a highly dynamic population structure and can be phenotypically and genetically differentiated into serogroups and clonal complexes. The aim of this study was to describe the phenotypic and genotypic characteristics of invasive isolates recovered in Colombia from 2013 to 2016. METHODOLOGY: A total of 193 invasive isolates were analyzed. Phenotypic and genotypic characteristics were determined by serotyping, antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. RESULTS: Based on the results, meningococcal serogroups C, B and Y were responsible for 47.9%, 41.7%, and 9.4% of cases, respectively, and the distribution of serogroups B and C changed over time. Fifteen clonal groups and 14 clonal complexes (cc) were identified by PFGE and genome sequencing. The main clonal group included serogroup B isolates with sequence type (ST)-9493 and its four single-locus variants, which has only been identified in Colombian isolates. The clonal population structure demonstrates that the isolates in this study mainly belong to four clonal complexes: ST-11 cc, ST-32 cc, ST-35 cc and ST-41/44 cc. Thirty-eight penA alleles were identified, but no correlation between MICs and specific sequences was observed. CONCLUSION: This study shows that most meningococcal isolates recovered from patients with invasive meningococcal disease in Colombia are strains associated with distinct globally disseminated hyperinvasive clones.


Asunto(s)
Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/genética , Neisseria meningitidis/genética , Adolescente , Adulto , Técnicas de Tipificación Bacteriana/métodos , Niño , Preescolar , Colombia/epidemiología , Electroforesis en Gel de Campo Pulsado/métodos , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neisseria meningitidis/aislamiento & purificación , Neisseria meningitidis/patogenicidad , Serogrupo , Serotipificación
12.
BMC Infect Dis ; 20(1): 525, 2020 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-32689953

RESUMEN

BACKGROUND: Neisseria meningitidis is a major cause of bacterial meningitis, and these infections are associated with a high mortality rate. Rapid and reliable diagnosis of bacterial meningitis is critical in clinical practice. However, this disease often occurs in economically depressed areas, so an inexpensive, easy to use, and accurate technology is needed. We performed a pooled-analysis to assess the potential of the recently developed loop-mediated isothermal amplification (LAMP) assay for detection of meningococcus. METHODS: Pubmed, Embase, and Web of Science were searched to identify original studies that used the LAMP assay to detect meningococcus. After pooling of data, the sensitivity and specificity were calculated, a summary receiver operating characteristic (SROC) curve was determined, and the area under the SROC curve was computed to determine diagnostic accuracy. Publication bias was assessed using Deek's funnel plot. RESULTS: We examined 14 studies within 6 publications. The LAMP assay had high sensitivity (94%) and specificity (100%) in the detection of meningococcus in all studies. The area under the SROC curve (0.980) indicated high overall accuracy of the LAMP assay. There was no evidence of publication bias. DISCUSSION: The LAMP assay has accuracy comparable to bacterial culture and PCR for detection of meningococcus, but is less expensive and easier to use. We suggest the adoption of the LAMP assay to detect meningococcus, especially in economically depressed areas.


Asunto(s)
Meningitis Meningocócica/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Neisseria meningitidis/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Exactitud de los Datos , Humanos , Meningitis Meningocócica/microbiología , Técnicas de Diagnóstico Molecular/economía , Técnicas de Amplificación de Ácido Nucleico/economía , Reacción en Cadena de la Polimerasa/economía , Reacción en Cadena de la Polimerasa/métodos , Curva ROC , Sensibilidad y Especificidad
16.
MMWR Morb Mortal Wkly Rep ; 69(24): 735-739, 2020 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-32555137

RESUMEN

Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 ß-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations.


Asunto(s)
Ciprofloxacino/farmacología , Farmacorresistencia Microbiana , Neisseria meningitidis/aislamiento & purificación , beta-Lactamasas/biosíntesis , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Neisseria meningitidis/efectos de los fármacos , Neisseria meningitidis/genética , Serogrupo , Estados Unidos , Adulto Joven
17.
BMC Infect Dis ; 20(1): 426, 2020 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-32552685

RESUMEN

BACKGROUND: A previous phase 2 study demonstrated the immunogenicity of a single dose of meningococcal A, C, W, Y-tetanus toxoid conjugate (MenACWY-TT) or polysaccharide (MenACWY-PS) vaccine for up to 5 years in individuals aged 11-55 years. This follow-up study evaluated long-term antibody persistence up to 10 years and the immunogenicity and safety of a single MenACWY-TT booster dose given 10 years after primary vaccination. METHODS: Blood draws were conducted annually in Years 7-10. At Year 10, all subjects received a MenACWY-TT booster dose. Blood was drawn at 1 month and safety data were collected ≤6 months postbooster. Study endpoints included immunogenicity during the persistence phase (primary), and immunogenicity and safety during the booster phase (secondary). Statistical analyses were descriptive. RESULTS: A total of 311 subjects were enrolled in the persistence phase (MenACWY-TT, 235; MenACWY-PS, 76); 220 were enrolled in the booster phase (MenACWY-TT, 164; MenACWY-PS, 56). Descriptive analyses indicated that at Years 7-10, the percentages of subjects achieving serum bactericidal antibody assay using baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128 were higher for serogroups A, W, and Y in the MenACWY-TT versus MenACWY-PS group; percentages were similar across groups for serogroup C. rSBA geometric mean titers (GMTs) for serogroups A, W, and Y were higher in the MenACWY-TT group and slightly higher in the MenACWY-PS group for serogroup C. One month postbooster, all primary MenACWY-TT and ≥98.1% of primary MenACWY-PS recipients had rSBA titers ≥1:8. For all serogroups, rSBA GMTs postbooster were higher in the MenACWY-TT versus MenACWY-PS group. Most local and general reactogenicity events were similar between groups and mild to moderate in severity. Adverse events at 1 month postbooster were 9.1% for the MenACWY-TT and 3.6% for the MenACWY-PS groups; all were nonserious. CONCLUSIONS: Immune responses to a single MenACWY-TT primary dose administered at age 11-55 years persisted in >70% of individuals evaluated at Years 7-10. A MenACWY-TT booster dose administered at Year 10 was safe and immunogenic with no new safety signals observed. These results provide important insights regarding long-term protection from primary vaccination and the benefits of booster dosing. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01934140. Registered September 2013.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Vacunas Meningococicas/inmunología , Adolescente , Adulto , Animales , Niño , Proteínas del Sistema Complemento , Hipersensibilidad a las Drogas , Femenino , Estudios de Seguimiento , Humanos , Inmunización Secundaria , Masculino , Persona de Mediana Edad , Neisseria meningitidis/inmunología , Conejos , Serogrupo , Factores de Tiempo , Vacunas Conjugadas/inmunología , Adulto Joven
18.
Nat Commun ; 11(1): 2823, 2020 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-32499480

RESUMEN

FinO-domain proteins are a widespread family of bacterial RNA-binding proteins with regulatory functions. Their target spectrum ranges from a single RNA pair, in the case of plasmid-encoded FinO, to global RNA regulons, as with enterobacterial ProQ. To assess whether the FinO domain itself is intrinsically selective or promiscuous, we determine in vivo targets of Neisseria meningitidis, which consists of solely a FinO domain. UV-CLIP-seq identifies associations with 16 small non-coding sRNAs and 166 mRNAs. Meningococcal ProQ predominantly binds to highly structured regions and generally acts to stabilize its RNA targets. Loss of ProQ alters transcript levels of >250 genes, demonstrating that this minimal ProQ protein impacts gene expression globally. Phenotypic analyses indicate that ProQ promotes oxidative stress resistance and DNA damage repair. We conclude that FinO domain proteins recognize some abundant type of RNA shape and evolve RNA binding selectivity through acquisition of additional regions that constrain target recognition.


Asunto(s)
Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Neisseria meningitidis/metabolismo , ARN Bacteriano/química , ARN Bacteriano/metabolismo , Regiones no Traducidas 3'/genética , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Secuencia de Bases , Daño del ADN , Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Neisseria meningitidis/genética , Conformación de Ácido Nucleico , Estrés Oxidativo , Unión Proteica , Estabilidad del ARN , ARN Mensajero/química , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/metabolismo , Reproducibilidad de los Resultados , Relación Estructura-Actividad
19.
Lancet ; 395(10240): 1865-1877, 2020 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-32534649

RESUMEN

Neisseria meningitidis is an obligate human commensal bacterium that frequently colonises the upper respiratory tract. Person-to-person transmission occurs via direct contact or through dispersion of respiratory droplets from a carrier of the bacteria, and can lead to invasive meningococcal disease. Rare sporadic cases of meningococcal urogenital and anorectal infections, including urethritis, proctitis, and cervicitis, have been reported, typically following orogenital contact with an oropharyngeal meningococcal carrier. The resulting infections were clinically indistinguishable from infections caused by Neisseria gonorrhoeae. Over the past two decades, there have also been multiple outbreaks across North America and Europe of invasive meningococcal disease among men who have sex with men (MSM). The responsible meningococci belong to a highly virulent and predominantly serogroup C lineage, including strains that are able to express nitrite reductase and grow in anaerobic environments, such as the urogenital and anorectal tracts. More recently, a distinct clade within this lineage has expanded to cause urethritis predominantly among men who have sex with women. Evolutionary events giving rise to this clade included the loss of the ability to express a capsule, and acquisition of several gonococcal alleles, including one allele encoding a highly efficient gonococcal nitrite reductase. Members of the clade continue to acquire gonococcal alleles, including one allele associated with decreased antibiotic susceptibility. This evolution has implications for the clinical and public health management of those who are infected and their close contacts, in terms of both antibiotic treatment, and prevention through vaccination.


Asunto(s)
Enfermedades Urogenitales Femeninas/epidemiología , Enfermedades Urogenitales Masculinas/epidemiología , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/transmisión , Neisseria meningitidis , Enfermedades del Recto/epidemiología , Enfermedades Bacterianas de Transmisión Sexual/epidemiología , Femenino , Enfermedades Urogenitales Femeninas/microbiología , Enfermedades Urogenitales Femeninas/prevención & control , Heterosexualidad , Homosexualidad Masculina , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Enfermedades Urogenitales Masculinas/microbiología , Enfermedades Urogenitales Masculinas/prevención & control , Infecciones Meningocócicas/prevención & control , Enfermedades del Recto/microbiología , Enfermedades del Recto/prevención & control , Enfermedades Bacterianas de Transmisión Sexual/prevención & control
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