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数学模型预测:未来耐多药(MDR)以及和广泛耐药(XDR)结核(TB)流行将在很大程度上取决于传播效率或耐药结核分枝杆菌较药物敏感菌株的相对适应性。比较耐药菌株和敏感菌株传播的分子流行病学研究产生了互相矛盾的结果:耐多药菌株和对药物全部敏感的菌株相比,传播性可高10倍以上或低10倍以下。使用实验模式生物完成的研究工作已经突出显示:细菌耐药的生物学复杂程度在标准的结核病传播的流行病学研究过程中通常不被考虑。最近使用结核分枝杆菌进行的实验研究表明,在这种生物中药物耐受可能同样复杂。摘要例如,结核分枝杆菌耐药菌株的相对适应性可以受到特定的耐药突变以及菌株遗传背景的影响。此外,补偿进化已经显示出在其他细菌中减轻耐药相关的适应性缺陷,可能是结核分枝杆菌耐药性出现和传播的重要因素。然而需要开展更多的工作,以了解这一病原菌耐药性相关的详细的分子机制和进化力量。这种知识的提高将能够更好地进行流行病学预测,有助于新工具和新策略的开发,以抗击耐药结核病。
Mathematical modeling predicts that the future prevalence of MDR and XDR tuberculosis (TB) will largely depend on the relative adaptability of transmission efficiency or drug-resistant Mycobacterium tuberculosis to drug-susceptible strains. Molecular epidemiological studies comparing the spread of drug-resistant and susceptible strains have produced conflicting results: multidrug-resistant strains can be more than 10-fold more or 10-fold less invasive than drug-susceptible strains. Research done using experimental model organisms has highlighted that the biological complexity of bacterial resistance is not usually accounted for in standard epidemiological studies of TB transmission. Recent experimental studies using M. tuberculosis have shown that drug tolerance in this organism may be equally complex. Abstract For example, the relative adaptability of M. tuberculosis-resistant strains can be influenced by specific resistance mutations and the genetic background of the strain. In addition, compensatory evolution has been shown to reduce resistance-related adaptive defects in other bacteria and may be an important factor in the emergence and spread of M. tuberculosis resistance. However, much more needs to be done to understand the detailed molecular mechanisms and evolutionary forces associated with the pathogen’s resistance. This increased knowledge will enable better epidemiological prediction and development of new tools and strategies to fight drug-resistant TB.