Gene Mutations In Aminoglycoside-resistant Mycobacterium Tuberculosis

The emergence of multidrug-resistant tuberculosis (MDR-TB) andextensively drug-resistant tuberculosis (XDR-TB) highlights the urgent need tounderstand the mechanisms of resistance to the drugs used to treat tuberculosis(TB). The aminoglycosides includes kanamycin and amikacin and so on areimportant bactericidal drugs used to treat MDR TB, and resistance to one orboth of these drugs may be extensively drug-resistant TB (XDR-TB).Second-line drug resistance mechanisms of aminoglycoside antibiotics inMycobacterium tuberculosis are the production of aminoglycoside-modifyingenzymes (AGMEs) and by the 16S rRNA mediated drug target change.In this study, representative enzymes were investigated. And second-linedrug-resistant strains of clinically isolated was the research object. Standardstrains of Mycobacterium tuberculosis H37Rv and susceptible strains of clinical isolates were compared with drug-resistant strains to find the relationshipbetween gene mutations and aminoglycosides resistance. This will help usunderstand the role of gene mutation in the mechanism ofaminoglycosides-resistant Mycobacterium tuberculosis.While Mycobacterium tuberculosis intruding into the host, the host's Tlymphocytes play a major function of the cellular immune defense. Changes ofT lymphocytes is often associated with the degree of effectiveness ofchemotherapy. Does this change of T lymphocytes happen in drug-resistancepatients? Based on clinical data, relevant researches were carried out.1 Gene mutations in aminoglycoside-resistant Mycobacterium tuberculosisInvestigations of the mechanism of enhanced invracellular survival (eis)gene, aminoglycoside acetyltransferase(aac) (2 ')-Ic gene and tlyA genemutations in aminoglycoside-resistance MTB were carried out. Strains of MTBwhich were resistant to isoniazid, rifampicin, ethambutol and streptomycin werechosen; the resistance to amikacin, kanamycin and capromycin were determinedby BACTEC MGIT 960; gene mutations were identified by PCR andsequencing.The results showed that there was eis gene mutation of G487A in 6 strainsand the amino acid changed from valine to isoleucine. The eis V163I mutationmight associate with aminoglycoside-resistance in MTB.Aac (2 ')-Ic gene mutations were not found in MTB clinical isolates. Westill need to increase the quantity of the sample or extend investigated genelength.TlyA gene synonymous mutation of the change from CTA to CTG happensin all the detected strains. Mutant strains of the drug resistance is not uniform,indicating that the mutations with resistance remains uncertain, but the high frequency of mutation may be related to M.tuberculosis pathogenic processes.Relationship between eis, aac(2 ')-Ic, tlyA gene mutations andaminoglycoside-resistance in MTB needs to be further elucidated.2 Analysis of T cells subsets in tuberculosis patientsSpecimens by clinical isolates in accordance with untreated or treatedpatients and drug resistance were grouped into initial treatment resistant group,initial treatment susceptible group, re-treatment-resistant group. Susceptibility ofMTB was identified by BACTEC MGIT 960 system; T lymphocyte subsetsCD3 ~+, CD4 ~+, CD8 ~+ cells in absolute and percentage, CD4 ~+ / CD8 ~+ values ofperipheral blood were determined by flow cytometry. All data were analysed bySPSS16.0 statistical software. Using multivariate analysis of variance(MANOVA), the significant differences between groups were analyzed, withP<0.05 as the standard statistically significant difference. The results showedthat T cells either in number or subtype had no difference between the groups.Due to small sample size is not enough to explain impact and effects of T cellimmunity in resistant Mycobacterium tuberculosis, so more clinical informationare needed to do more further research.