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Muhamed-kheir Taha - One of the best experts on this subject based on the ideXlab platform.
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Molecular Characterization of Invasive Isolates of Neisseria meningitidis in Casablanca, Morocco.
Journal of Clinical Microbiology, 2018Co-Authors: Aziza Razki, Eva Hong, Ala-eddine Deghmane, Khalid Zerouali, Houria Belabbes, Khadija Aitmouss, Aude Terrade, Bahija Zaki, Naima Elmdaghri, Muhamed-kheir TahaAbstract:Meningococcal epidemiology may change unpredictably, and typing of Neisseria meningitidis isolates is crucial for the surveillance of invasive meningococcal disease (IMD). Few data are available regarding the meningococcal epidemiology in countries of North Africa. We aimed to explore invasive meningococcal isolates from the Casablanca region in Morocco. We used whole-genome sequencing (WGS) to characterize 105 isolates from this region during the period of 2011 to 2016. Our data showed that the majority (n = 100) of the isolates belonged to serogroup B. Genotyping indicated that most of the isolates (n = 62) belonged to sequence type 33 of clonal complex 32. The isolates also showed the same PorA and FetA markers and clustered together on the basis of WGS phylogenetic analysis; they seemed to correspond to an expansion of local isolates in the Casablanca region, as reported for similar isolates in several other countries. These data suggest that serogroup B isolates may predominate in Morocco, which may have an important impact in the design of vaccination strategies.
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Comparison of the inflammatory response of brain microvascular and peripheral endothelial cells following infection with Neisseria meningitidis.
Pathogens and Disease, 2017Co-Authors: Julia Dick, Muhamed-kheir Taha, Sabrina Hebling, Jérôme Becam, Alexandra Schubert-unkmeirAbstract:The interaction of Neisseria meningitidis with both peripheral and brain endothelial cells is a critical event in the development of invasive meningococcal disease. In this study, we used in vitro models based on human brain microvascular endothelial cells (HBMEC), and peripheral endothelial EA.hy926 cells, to investigate their roles in the inflammatory response towards meningococcal infection. Both cell lines were infected with two pathogenic N. meningitidis isolates and secretion of the cytokine interleukin-6 (IL-6), the CXC chemokine IL-8 and the monocyte chemoattractant protein-1 (MCP-1) were estimated by ELISA. Neisseria meningitidis was able to stimulate the production of IL-6 and IL-8 by HBMEC and EA.hy926 cells in a time- and concentration-dependent manner. Interestingly, HBMEC released significant higher amounts of IL-6 and IL-8. Moreover, we observed that heat-killed bacteria stimulated high levels of IL-8. In addition, capsule expression had an inhibitory effect on IL-8 release. We extended our study and included serogroup C strains belonging to sequence type 11 clonal complex (cc) from a recent outbreak in France, as well as isolates belonging to the hypervirulent clonal complexes cc8, cc18, cc32 and cc269 and analyzed their ability to induce the secretion of IL-8 from both cell lines. Although individual variations were observed among different isolates, no clear correlations were observed between strain origin, clinical presentation and IL-8 levels.
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Resurgence of Neisseria meningitidis serogroup W ST-11 (cc11) in Madagascar, 2015–2016.
International Journal of Infectious Diseases, 2017Co-Authors: Saïda Rasoanandrasana, Eva Hong, Mihaja Raberahona, Milen Milenkov, Mbolanirina Lala Rakotomahefa Narison, Felana Ranaivo Rabetokotany, Luc Rakotovao, Mamy Jean De Dieu Randria, Gláucia Paranhos-baccalà, Muhamed-kheir TahaAbstract:The resurgence of invasive meningococcal disease caused by Neisseria meningitidis serogroup W with sequence type ST-11 (cc11) was observed in Madagascar in 2015-2016. Three cases were investigated in this study. Molecular characterization of the strains suggests the local transmission of a single genotype that may have been circulating for years.
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Transport and Catabolism of Carbohydrates by Neisseria meningitidis.
Journal of Molecular Microbiology and Biotechnology, 2016Co-Authors: Meriem Derkaoui, Ala-eddine Deghmane, Ana Antunes, Jamila Nait Abdallah, Sandrine Poncet, Alain Mazé, Que Mai Ma Pham, Abdelhamid Mokhtari, Philippe Joyet, Muhamed-kheir TahaAbstract:We identified the genes encoding the proteins for the transport of glucose and maltose in Neisseria meningitidis strain 2C4-3. A mutant deleted for NMV_1892(glcP) no longer grew on glucose and deletion of NMV_0424(malY) prevented the utilization of maltose. We also purified and characterized glucokinase and α-phosphoglucomutase, which catalyze early catabolic steps of the two carbohydrates. N. meningitidis catabolizes the two carbohydrates either via the Entner-Doudoroff (ED) pathway or the pentose phosphate pathway, thereby forming glyceraldehyde-3-P and either pyruvate or fructose-6-P, respectively. We purified and characterized several key enzymes of the two pathways. The genes required for the transformation of glucose into gluconate-6-P and its further catabolism via the ED pathway are organized in two adjacent operons. N. meningitidis also contains genes encoding proteins which exhibit similarity to the gluconate transporter (NMV_2230) and gluconate kinase (NMV_2231) of Enterobacteriaceae and Firmicutes. However, gluconate might not be the real substrate of NMV_2230 because N. meningitidis was not able to grow on gluconate as the sole carbon source. Surprisingly, deletion of NMV_2230 stimulated growth in minimal medium in the presence and absence of glucose and drastically slowed the clearance of N. meningitidis cells from transgenic mice after intraperitoneal challenge.
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Neisseria meningitidis Serogroup X in Sub-Saharan Africa.
Emerging Infectious Diseases, 2016Co-Authors: Alain Agnememel, Eva Hong, Dario Giorgini, Viginia Nuñez-samudio, Ala-eddine Deghmane, Muhamed-kheir TahaAbstract:The epidemiology of meningococcal disease varies by geography and time. Whole-genome sequencing of Neisseria meningitidis serogroup X isolates from sub-Saharan Africa and Europe showed that serogroup X emergence in sub-Saharan Africa resulted from expansion of particular variants within clonal complex 181. Virulence of these isolates in experimental mouse models was high.
Dominique A. Caugant - One of the best experts on this subject based on the ideXlab platform.
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Neisseria meningitidis: using genomics to understand diversity, evolution and pathogenesis
Nature Reviews Microbiology, 2020Co-Authors: Dominique A. Caugant, Ola B. BrynildsrudAbstract:Meningococcal disease remains an important cause of morbidity and death worldwide despite the development and increasing implementation of effective vaccines. Elimination of the disease is hampered by the enormous diversity and antigenic variability of the causative agent, Neisseria meningitidis , one of the most variable bacteria in nature. These features are attained mainly through high rates of horizontal gene transfer and alteration of protein expression through phase variation. The recent availability of whole-genome sequencing (WGS) of large-scale collections of N. meningitidis isolates from various origins, databases to facilitate storage and sharing of WGS data and the concomitant development of effective bioinformatics tools have led to a much more thorough understanding of the diversity of the species, its evolution and population structure and how virulent traits may emerge. Implementation of WGS is already contributing to enhanced epidemiological surveillance and is essential to ascertain the impact of vaccination strategies. This Review summarizes the recent advances provided by WGS studies in our understanding of the biology of N. meningitidis and the epidemiology of meningococcal disease. Meningococcal disease remains an important cause of morbidity and death worldwide despite the development and increasing implementation of effective vaccines. In this Review, Caugant and Brynildsrud discuss how high-throughput sequencing approaches have advanced our understanding of the diversity and evolution of Neisseria meningitidis and the pathogenesis of N. meningitidis infection and how they are helping to explain the epidemiology of meningococcal disease.
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genetics and evolution of Neisseria meningitidis importance for the epidemiology of meningococcal disease
Infection Genetics and Evolution, 2008Co-Authors: Dominique A. CaugantAbstract:Abstract Meningococcal disease is a life-threatening illness occurring worldwide with incidence rates varying from 1 to 1000 cases per 100 000. The causative organism, Neisseria meningitidis, is a normal commensal of humans. While strains associated with asymptomatic carriage are highly diverse, a few hyper-invasive genetic clones of the species may spread rapidly through human populations, resulting in countrywide epidemics of meningococcal meningitis. N. meningitidis fitness for spread and colonization is directly linked to the capability of the bacterium to change its genome and adapt to its environment, by means of a variety of genetic mechanisms. This review addresses some of the impacts of the evolutionary potential of N. meningitidis on the occurrence of meningococcal disease.
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interlaboratory comparison of pcr based identification and genogrouping of Neisseria meningitidis
Journal of Clinical Microbiology, 2005Co-Authors: Muhamed-kheir Taha, Jean-michel Alonso, Dominique A. Caugant, Mary Cafferkey, Stuart C Clarke, M A Diggle, Andrew S Fox, Matthias FroschAbstract:Twenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries. Ten of these laboratories are participating in the EU-MenNet program (a European Union-funded program) and are members of the European Monitoring Group on Meningococci. The remaining laboratory was located in Burkina Faso. Neisseria meningitidis was sought by detecting several meningococcus-specific genes (crgA, ctrA, 16S rRNA, and porA). The PCR-based nonculture method for the detection of N. meningitidis gave similar results between participants with a mean sensitivity and specificity of 89.7 and 92.7%, respectively. Most of the laboratories also performed genogrouping assays (siaD and mynB/sacC). The performance of genogrouping was more variable between laboratories, with a mean sensitivity of 72.7%. Genogroup B gave the best correlation between participants, as all laboratories routinely perform this PCR. The results for genogroups A and W135 were less similar between the eight participating laboratories that performed these PCRs.
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Neisseria meningitidis an overview of the carriage state
Journal of Medical Microbiology, 2004Co-Authors: Siamak Pour Yazdankhah, Dominique A. CaugantAbstract:During periods of endemic disease, about 10 % of the general population harbour Neisseria meningitidis in the nasopharynx. Since N. meningitidis is a strict human pathogen and most patients have not been in contact with other cases, asymptomatic carriers are presumably the major source of the pathogenic strains. Most carrier isolates are shown to lack capsule production. The capsule deficient state of meningococcal strains in the nasopharynx may aid evasion of the human immune defence and hence be selected to survive nasopharyngeal colonization. Carriage itself can be an immunizing process resulting in systemic protective antibody responses. Frequent nasopharyngeal colonization with related bacteria like Neisseria lactamica improves natural immunity to meningococci by the formation of cross-reacting antibodies. While most meningococcal strains recovered from patients belong to a limited number of clonal groups worldwide, strains isolated from carriers comprise numerous genotypes, with only a small proportion of the strains representing invasive clones. During the carriage state, co-colonization with other pathogenic and non-pathogenic bacteria may lead to genetic exchange, which may result in the emergence of new meningococcal clones. The high diversity of meningococcal carrier strains, compared with hypervirulent strains, supports the idea that transmissibility, not invasion, is essential in the life cycle of N. meningitidis.
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population genetics and molecular epidemiology of Neisseria meningitidis
Apmis, 1998Co-Authors: Dominique A. CaugantAbstract:Under non-epidemic conditions, Neisseria meningitidis causes disease primarily in children under the age of 5 and the cases are sporadic without any evident relationship between them. Occasionally, localized outbreaks of meningococcal disease occur, and sometimes epidemic waves of disease may spread to several countries or even continents and constitute a pandemic. In the past 10 years or so, population genetic analyses have provided insights into the biology of the bacterium and the epidemiology of meningococcal disease, improving our understanding of the cause of epidemics. Through the application of molecular methods, and especially multilocus enzyme electrophoresis, to N. meningitidis strains of worldwide origin, it has been possible to identify virulent clones and provide a surveillance system to warn of meningococcal epidemics. The characteristics of the predominant clones which are nowadays causing meningococcal disease in the world are summarized here and the importance of population genetics in interpreting the epidemiological data is illustrated.
Alliluev A.p. - One of the best experts on this subject based on the ideXlab platform.
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Isolation and determination of the activity of IgA1 protease from Neisseria meningitidis
'Pleiades Publishing Ltd', 2020Co-Authors: Zhigis L.s., Razgulyaeva O.a., Zueva V.s., Melnikov E.e., Zubov V.p., Kozlov L.v., Bichucher A.m., Kotel'nikova O.v., Alliluev A.p.Abstract:A method of the isolation and purification of IgA1 protease from a culture of Neisseria meningitidis serogroup A has been developed. Three inactivated intermediates of the production of the meningococcal vaccine, a culture liquid, as well as a supernatant and precipitate obtained by the precipitation of bacterial cells by cetavlon, served as a starting material. The purity of IgA1 protease was determined by SDS-PAGE. An immunoenzyme assay for determining the IgA1 protease activity has been developed. The yield of the enzyme with a specific activity of 0.5 to 4 million units/mg from 103 g of the cetavlon precipitate (40 l of culture liquid) was about 600 μg. It was shown that IgA1 protease isolated from serogroup A meningococcus is capable of protecting experimental animals (mice) infected with meningococcus of serogroup B. © 2010 Pleiades Publishing, Ltd
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Induction of antimeningitis immunity by synthetic peptides. III. Immunoactive synthetic fragments of the NspA protein from Neisseria meningitidis
2020Co-Authors: Koroev D.o., Kotel'nikova O.v., Oboznaya M.b., Zhmak M.n., Volkova T.d., Lakhtina O.e., Vol'pina O.m., Nesmeyanov V.a., Alliluev A.p.Abstract:Four potentially immunoactive peptide fragments of the NspA protein from the outer membrane of the bacterium Neisseria meningitidis were synthesized in order to create a synthetic vaccine against the meningococcal infection by the serogroup B bacterium. Mice of various lines were immunized with the free peptides nonconjugated with a protein carrier. All the synthetic peptides were shown to induce the production of the antipeptide antibodies in mice. A peptide capable of inducing a decrease in the number of bacteria in blood and the protection of infected animals from death was found in the experiments on the protection of the animals infected with two strains of the Neisseria meningitidis serogroup B
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Induction of antimeningitis immunity by synthetic peptides: III. Immunoactive synthetic fragments of the NspA protein from Neisseria meningitidis
'Springer Science and Business Media LLC', 2020Co-Authors: Koroev D.o., Kotel'nikova O.v., Oboznaya M.b., Zhmak M.n., Volkova T.d., Lakhtina O.e., Vol'pina O.m., Nesmeyanov V.a., Alliluev A.p.Abstract:Four potentially immunoactive peptide fragments of the NspA protein from the outer membrane of the Neisseria meningitidis bacterium were synthesized in order to create a synthetic vaccine against meningococcal infection by the serogroup B bacterium. Mice of various lines were immunized with free peptides nonconjugated with a protein carrier. All the synthetic peptides were shown to induce the production of the antipeptide antibodies in mice. A peptide capable of inducing a decrease in the number of bacteria in blood and the protection of infected animals from death was found in the experiments on the protection of the animals infected with two strains of the Neisseria meningitidis serogroup B
Marzia Monica Giuliani - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of meningococcal b vaccine against endemic hypervirulent Neisseria meningitidis w strain england
Emerging Infectious Diseases, 2016Co-Authors: Shamez N Ladhani, Alessia Biolchi, Marzia Monica Giuliani, Mariagrazia Pizza, Kazim Beebeejaun, Jay Lucidarme, Jamie Findlow, Mary Ramsay, Ray BorrowAbstract:Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain.
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recognition of Neisseria meningitidis by the long pentraxin ptx3 and its role as an endogenous adjuvant
PLOS ONE, 2015Co-Authors: Barbara Bottazzi, Marzia Monica Giuliani, Laura Santini, Silvana Savino, Ana I Diez, Giuseppe Mancuso, Concetta Beninati, Marina Sironi, Sonia Valentino, Livija DebanAbstract:Long pentraxin 3 (PTX3) is a non-redundant component of the humoral arm of innate immunity. The present study was designed to investigate the interaction of PTX3 with Neisseria meningitidis. PTX3 bound acapsular meningococcus, Neisseria-derived outer membrane vesicles (OMV) and 3 selected meningococcal antigens (GNA0667, GNA1030 and GNA2091). PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions. Ptx3-deficient mice had a lower antibody response in vaccination protocols with OMV and co-administration of PTX3 increased the antibody response, particularly in Ptx3-deficient mice. Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis. These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.
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Neisseria meningitidis gna2132 a heparin binding protein that induces protective immunity in humans
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Davide Serruto, Tiziana Spadafina, Laura Ciucchi, Lisa A Lewis, Marta Tontini, Alessia Biolchi, Kate L Seib, Marzia Monica Giuliani, Laura Santini, John J. DonnellyAbstract:GNA2132 is a Neisseria meningitidis antigen of unknown function, discovered by reverse vaccinology, which has been shown to induce bactericidal antibodies in animal models. Here we show that this antigen induces protective immunity in humans and it is recognized by sera of patients after meningococcal disease. The protein binds heparin in vitro through an Arg-rich region and this property correlates with increased survival of the unencapsulated bacterium in human serum. Furthermore, two proteases, the meningococcal NalP and human lactoferrin, cleave the protein upstream and downstream from the Arg-rich region, respectively. We conclude that GNA2132 is an important protective antigen of N. meningitidis and we propose to rename it, Neisserial Heparin Binding Antigen (NHBA).
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nada a novel vaccine candidate of Neisseria meningitidis
Journal of Experimental Medicine, 2002Co-Authors: Maurizio Comanducci, Marzia Monica Giuliani, Laura Santini, Stefania Bambini, Brunella Brunelli, Jeannette Adubobie, Beatrice Arico, Barbara Capecchi, Vega Masignani, Silvana SavinoAbstract:Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, is still a major cause of mortality due to sepsis and meningitis. Here we describe NadA, a novel surface antigen of N. meningitidis that is present in 52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37, ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N. gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The guanine/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three well-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), forms high molecular weight oligomers, and binds to epithelial cells in vitro supporting the hypothesis that NadA is important for host cell interaction. NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages.
David S Stephens - One of the best experts on this subject based on the ideXlab platform.
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good news and bad news 4cmenb vaccine for group b Neisseria meningitidis
The New England Journal of Medicine, 2020Co-Authors: Lee H Harrison, David S StephensAbstract:Neisseria meningitidis remains a major cause of meningitis, sepsis, and other serious infections globally. Almost all meningococcal infections are caused by one of six capsular groups (A, B, C, W, ...
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Neisseria meningitidis biology microbiology and epidemiology
Methods of Molecular Biology, 2012Co-Authors: Nadine Rouphael, David S StephensAbstract:Neisseria meningitidis (the meningococcus) causes significant morbidity and mortality in children and young adults worldwide through epidemic or sporadic meningitis and/or septicemia. In this review, we describe the biology, microbiology, and epidemiology of this exclusive human pathogen. N.meningitidis is a fastidious, encapsulated, aerobic gram-negative diplococcus. Colonies are positive by the oxidase test and most strains utilize maltose. The phenotypic classification of meningococci, based on structural differences in capsular polysaccharide, lipooligosaccharide (LOS) and outer membrane proteins, is now complemented by genome sequence typing (ST). The epidemiological profile of N. meningitidis is variable in different populations and over time and virulence of the meningococcus is based on a transformable/plastic genome and expression of certain capsular polysaccharides (serogroups A, B, C, W-135, Y and X) and non-capsular antigens. N. meningitidis colonizes mucosal surfaces using a multifactorial process involving pili, twitching motility, LOS, opacity associated, and other surface proteins. Certain clonal groups have an increased capacity to gain access to the blood, evade innate immune responses, multiply, and cause systemic disease. Although new vaccines hold great promise, meningococcal infection continues to be reported in both developed and developing countries, where universal vaccine coverage is absent and antibiotic resistance increasingly more common.
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biology and pathogenesis of the evolutionarily successful obligate human bacterium Neisseria meningitidis
Vaccine, 2009Co-Authors: David S StephensAbstract:For at least two hundred years, Neisseria meningitidis (the meningococcus), the cause of epidemic meningitis and sepsis, has inflicted rapid death, disability and fear on disparate human populations. The meningococcus is also recognized as a highly successful commensal organism exclusively found in humans. The evolution of N. meningitidis as an exclusive human commensal and sometimes a fulminant and fatal pathogen represents an important case study in microbial pathogenesis. We review the general status of our knowledge of pathogenesis of meningococcal carriage, transmission and virulence behavior with particular emphasis on the relevance of research on this topic to vaccine development.
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capsule switching of Neisseria meningitidis
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: John S Swartley, A A Marfin, Srilatha Edupuganti, Lijun Liu, P Cieslak, B Perkins, J D Wenger, David S StephensAbstract:The different sialic acid (serogroups B, C, Y, and W-135) and nonsialic acid (serogroup A) capsular polysaccharides expressed by Neisseria meningitidis are major virulence factors and are used as epidemiologic markers and vaccine targets. However, the identification of meningococcal isolates with similar genetic markers but expressing different capsular polysaccharides suggests that meningococcal clones can switch the type of capsule they express. We identified, except for capsule, isogenic serogroups B [(α2→8)-linked polysialic acid] and C [(α2→9)-linked polysialic acid] meningococcal isolates from an outbreak of meningococcal disease in the U. S. Pacific Northwest. We used these isolates and prototype serogroup A, B, C, Y, and W-135 strains to define the capsular biosynthetic and transport operons of the major meningococcal serogroups and to show that switching from the B to C capsule in the outbreak strain was the result of allelic exchange of the polysialyltransferase. Capsule switching was probably the result of transformation and horizontal DNA exchange in vivo of a serogroup C capsule biosynthetic operon. These findings indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching. Capsule switching may be an important virulence mechanism of meningococci and other encapsulated bacterial pathogens. As vaccine development progresses and broader immunization with capsular polysaccharide conjugate vaccines becomes a reality, the ability to switch capsular types may have important implications for the impact of these vaccines.
