Gene Polymorphisms Of Mycobacterium Tuberculosis EsxA,Esxh,and FbpB Genes Among Clinical Isolates In Children's Tuberculosis

Objective: To study the polymorphisms in antigen encoding genes esxA ? fbpB and Rv2660 c among clinical isolates of children tuberculosis,and understand the epitope polymorphisms of the human T and B cell epitopes in them to evaluate the influence on the effectiveness of H56 vaccine.Methods: 135 strains were selected from the infection department of children's hospital of Chongqing from 2006 to 2013,and amplified gene sequences of esxA?fbpB?Rv2660c by PCR respectively,the sequences were compared together with the gene sequences of standard strain H37 Rv and the human T and B cell epitope sequences from Immune Epitope Database(IEDB),then we assessed genetic diversities of gene sequences in esxA?fbpB?Rv2660c between Beijing genotype strains and non-Beijing genotype strains based on the genotyping in the pre-study.The dN and d S value of human T/B cell epitope regions and non-epitope regions were calculated for evaluating the environment pressure according to the mutations in the target genes.Results: Among 135 strains,no gene polymorphisms were found in esxA?Rv2660c,gene sequences of them were conservative.While fbpB had genetic diversities in 66 clinical isolates,there were 5 single nucleotide polymorphism(SNP)mutations in fbpB which affected 9(14.81%)B cell epitopes and 8 T cell epitopes areas.The dN?dS value of whole fbpB gene were 0.000120 and 0.002126,those of T epitopes were 0.000067 and 0.002382 respectively,those of non-T epitopes area were 0.000408 and 0.000470,the dN?dS value of B epitopes areas were 0.000063 and 0.002380,and those of non-B epitopes areas were 0.Conclusion: The gene sequences of esxA ? Rv2660 c were conservative,the sequences of fbpB contain genetic diversities especially in Beijing genotype strains which may influence the structure and function of antigen Ag85 B,we suggest that the gene polymorphisms may affect the efficacy of vaccine H56.The human T and B cell epitopes of fbpB also have polymorphisms,but there is no immune evasion indicated that fbpB is purify selected in the interaction with the host environment.