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Genetic Characteristics Of Nongroupable Neisseria Meningitidis In China

Posted on:2016-09-24Degree:MasterType:Thesis
Country:ChinaCandidate:Z XuFull Text:PDF
GTID:2284330482955589Subject:Pathogen Biology
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Neisseria meningitidis (Nm), a strictly human pathogen that asymptomatically colonizes the upper respiratory tract in the human population. is a leading cause of invasive bacterial infections globally, with devastating morbidity and mortality. This baterium transmits through aerosol, droplet and close contact. The respiratory tract is usually the first to be exposed to this bacterium. About 10 percent of people carry Neisseria meningitidis asyptomatically in their throats but harmlessly. Once the bacterium gains access to blood and cerebral spinal fluid across the barriers, it will cause severe infectious disease.Almost all the Neisseria meningitidis strains which can cause invasive disease have the capsule, or surrounded by capsular polysaccharide. Based on the biochemical composition of capsular polysaccharides,12 serogroups are currently recognized. Along with the encapsulated strains, some isolates can not be identified to a specific serogroup and referred to as nongroupable, this is due to the capsule deficient. Being nongroupable can be due to inactivation or absence of capsule synthesis genes by three genetic mechanisms. Class I:Nongroupable islates were genetically serogroup Y, B or C isolates that did bot express capsule but were related to groupable isolates found in the population; Class II:capsule deficient because of insertion element-associated deletions of capsule biosynthesis genes; Class III:isolates the lacked all capsule genes and formed a distinct genetic cluster not associated with meningococcal disease. Capsule is also the target of the host mucosal immune system, the capsule deficience of nongroupable Neisseria meningitidis is benefit for the strains’ colonization and invasion. In addition, long-term colonization of nongroupable Neisseria meningitidis strains in the human nasopharynx provides a rich gene "receptor bacteria library" and "donor bacteria library " for Neisseria meningitidis horizontal gene transfer and recombination. Genetic recombination and horizontal transfer provides the possibility for new strains of Neisseria meningitidis production. After gene recombination, high pathogenicity strains can cause epidemic. Usually, invasive disease caused by nongroupable Neisseria meningitidis is associated with immunocompromised individual. But the proportion of nongroupable Neisseria meningitidis is raising year by year in our country every year meningococcal carriage investigation. So the study of typing and genetic characteristics of nongroupable Neisseria meningitidis has important significance in public health.First of all, a total of 104 Neisseria meningitidis strains, isolated from 17 provinces from 2005 to 2011, were investigated by using MLST, PCR and the gene sequencing. The genogroup of 104 NG N.meningitidis strains included cnl(capsule null locus) (n=36), genogroup B (n=20), genogroup C (n=14), genogroup W (n=9), genogroup E (n=9), genogroup X (n=3) and genogroup Y (n=3), there were 10 strains which could not be genogrouped. None of the NG isolates were belonging to other genogroups. By MLST analysis,104 NG N.meningitidis were identified to belong to 44 clonal complexs,14 of which were new sequence types; 17 sequence types can be grouped into 7 clonal complexs (n=65); cnl strains all belong to CC198, the dominant ST complex of genogroup B and genogroup C was CC4821,CC11 and CC174 were the major ST complexs of genogroup W strains. The N. meningitidis NG strains in China showed significant gene polymorphism, and the CC198 complex strains all serogrouped as cnl strains.Genome analyse of Neisseria spp. were using BLAST, MEGA 4.0 and Recombination Detection Program 4. Osoftware. While analyzing the phylogenetic relationships of N. meningitidis, we selected 28 genomes, including all of the 23 N. meningitidis (18 encapsulated and 5 cnl strains),4 N. gonorrhoeae, and 1 N. lactamica genomes. Using 75071 single nucleotide polymorphisms located in 1163 core genes, we deduced the phylogenetic relationship of a batch of representative N. meningitidis genomes. The CC198 and CC1136 were clustered together but apart from other N. meningitidis strains including CC53. We also aligned the sequences of genes located in regions D and E of the capsule gene locus from encapsulated and unencapsulated strains. A number of possible recombination events were identified in galE and tex genes between different serogroups of encapsulated N. meningitidis and CC53strains, especially in tex. In contrast, there is almost no recombination in N. lactamica, N. gonorrhoeae and N. meningitidis CC198 strains. These results showed that CC198 belongs to an phylogenetically distinctive group within the species of N. meningitidis, which may be derived from the cnl type ancestor of N. meningitidis directly. The encapsulated strains may acquire other necessary genes for capsule by horizontal transfer.In summary, the cnl strains in China all s all belong to CC198, and CC198 belongs to an phylogenetically distinctive group within the species of N. meningitidis.
Keywords/Search Tags:Neisseria Meningitidis, Nongroupable, molecular typing, cnl, CC198
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