简介：AbstractThe low success rates in the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB), which account for 55% and 34% respectively, led the WHO to conclude that MDR/XDR-TB is a serious public health crisis. However, the virulence of MDR/XDR-Mycobacterium Tuberculosis(Mtb) has not been analyzed in details, which could provide a specific guidance for the control and prevention. In this review, we discuss different aspects of MDR/XDR-Mtb virulence and its relationship to fitness cost by probing the following questions: (1) what mediates the virulence of MDR/XDR-Mtb? (What is the relationship between fitness and virulence of Mtb? (2) Is it possible that drug-resistant Mtb(DR Mtb) can show higher fitness? (3) What is the definite effect on fitness of each drug-resistant mutant? (4) What other important factors affecting fitness in the mutant strain? (5) How to study the virulence of a large number of DR Mtb?And what prevention and control measures will be taken in the future, especially for the high virulent DR Mtb? We therefore summarized the congruent relationship between drug resistance and fitness from the global response-related genes to antibiotic resistance-contributing mutation, provided methods to explore the virulence of DR Mtb. This review may offer some critical information and concise guide to creating strategies for the prevention and control of drug-resistant Mtb.

简介：AbstractBackground:Immune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population.Methods:We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis.Results:We observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152-1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055-1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349-0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087-1.793) effect against the development of TB.Conclusions:This study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future.