《制药工程专业英语》Unit9,P96-98.doc

所选译文位置：制药工程专业英语Unit9，P96-98外文文献原稿和译文原 稿Throughout recorded history ，bacterial infections have periodically exacted heavy tolls on the human population .During “Black Death”bubonic plague episode of 1347-1351.Yersinia pestis killed an estimated 25 million in Asia and Europe .US PublicHeath Service statistics for 1910 and 1920 show that early in this century tuberculosis killed one in every 1000 US residents . Even today ,mainly in developing countries ,Mycobacterium tuberculosis remains the leading cause of death attributable to a single infectious agent, killing over three million people worldwide every year.Within just a few decades, the availability of an anti-infective pharmacopoeia suddenly provided humans with the potential to circumvent Natures time-tested, live-or-die evolutionary paradigm for enhancing their survival prospects under constant microbial barrage. Those members that previously would have succumbed could now survive longer with the help of vaccines and antibiotics - auxiliary agents which work alongside the immune system to fight infection. In effect, humans employment of these auxiliaries can be looked upon as exemplifying a self-contrived evolution in their immunological defense system. Once the usefulness of Sir Alexander Flemings penicillin discovery had been demonstrated, a flurry of other antibiotics unearthed from natural sources followed. Some of these proved suitable for treating disease, usually after chemical modification to improve the natural compounds potency, safety or pharmacokinetic profiles. For most of the past 50 years, it seemed that medical science had gained a strong upper hand over bacterial disease. Some pharmaceutical houses and funding agencies decided to cut back on antibiotic discovery efforts, as it appeared that the physicians antibacterial arsenal was well stocked. But the nature of the diseases has proved otherwise. The rapid escalation in the incidence of multiple-antibiotic-resistant pathogens is now raising very serious concerns worldwide.This development underscores the powerful evolutionary capabilities of bacterial populations under the selective pressure imposed by antibiotic therapy . Antibiotic resistance Resistance problems are seen with both Gram-negative(for example Escherichia coli) and Gram-positive bacteria (such as Staphylococcus aureus), but most of the concerns are with the latter group of pathogens.Streptococcus is a respiratory Gram-positive pathogen responsible for 40,000 deaths a year in the US alone. A rapidly rising prevalence of penicillin-resistant S. pneumoniae infections is now problematic in many countries. One of the worst situations is in Hungary, where 70%of the S. from children tested in 1988-1989 were resistant to penicillin.Bacteria have evolved numerous ploys for defeatng antibiotic actionthey inactivate the antibiotic by hydrolysis, acylation , phosphorylation or nucleotidylation reactions; aitre the antibiotics target site; or reduce the intracellular drug concentration by decreasing membrane permeability and/or actively pumping the drug out of the cell . With improved understanding of these mechanisms of resistance through molecular biology and biochemical techniques, medicinal chenmists have been provided with the targets for attempting to circumvent some of the resistance problems.A predominant resistance mechanism against the B-lactam drugs (such as Penicillin) involves enzymatic cleavage of the B-lactam ring. While the drug Methicillin was developed because it could withstand such action, strains of Methicillin-resistance S.ayreus (MRSA) emerged in 1961 , jusr two years after the drug first went into wide use . MRSA strains evolved so that they had an additional drug-target protein involved with cell wall biosynthesis, and this altered protein has a very low affinity for virtually all B-lactams. To make matters worse, mose MRSA strains are also resistant to many other classes of antibiotics,with the exception of the glycopeptide Vancomycin. Now seen around the globe, MRSA strains are very problematic in Japan ( where in some hospitials 60% of S. Aureus isolates are MRSA ), as well as in Spain , France , Italy and the US , each with a greater than 30% incidence.A particularly disturbing milestone was the 1988 emergence of Vancomycin-resistant enterococci (VRE). Some VRE now dont respond to any available antibiotics. The enterococci have become the second mose frequently encountered hospital acquired pathogne in the US, where the incidence of VRE strains is now about 15% of all clinical enterococcal isolates . Resistance to Vancomycin arises because a D-alanine-D-lactate residue ( which vancomycin binds to only poorly) has been substituted for the D-alanine-D-alanine residue normally found at the rerminus of a pentapeptide precursor involved in the bacterias cell wall biosynthesis. There is now a great concern that the genes conferring resistance in VRE to glycopeptides like Vancomycin will be naturally transferred to S.aureus, has been experimentally demonstrated feasible by William Noble at St Thomas Hospital, London. As Vancomycin is the drug of last resort for treating MRSA infections, the anticipated natural acquisition of Vancomycin resistance in this virulent pathogen would result in the sobering return to pre-antibiotic era therapeutic failures, should no alternate effective therapy become available. ConclusionsMans use of antibiotics has rapidly accelerated the dynamic evolutionary interplay between humans and bacteria. The recent rapid rise in multidrug-resistant Gram-positive bacterial infections worldwide has sounded a loud claxon for the need of new, effective therapies. The newer agents described here may provide physicians with a refurbished arsenal. The discovery of new bacterial drug targets through genomic research, as well as improvements in our understanding of bacterial resistant mechanisms, hold promise for the discovery of new means of treating multidrug-resistant bacterial infections. Given enough time, bacteria will eventually be able to develop resistance to any new antibacterial agent. Those drugs that can attack the pathogen through a novel mechanism may have reduced propensities to rapid resistance development. 译 文纵观历史记载，细菌感染的人口定期付出沉重的收费。鼠疫菌的“黑死病”鼠疫的1347-1351期间，估计有25万人在亚洲和欧洲死亡。美国公共卫生服务统计为1910年和1920年的节目，在这个早在本世纪结核病死亡每1000名美国居民中的一个。即使在今天，主要是在发展中国家，结核分枝杆菌仍然是主要死亡原因由于在单染性病，全世界每年杀害超过三百万整个脊椎动物进化过程中的这种不懈的微生物攻击，挑起了一个令人惊讶的复杂的保护性免疫系统的进化。随着人类的外观，最终到达一个物种可以设法协助先天和后天免疫系统，避免感染。通过利用微生物的抗原成分（疫苗和马血清抗毒素的产生），然后微生物次生代谢产物（抗生素），已成为人类善于预防和治疗许多以前致命的微生物疾病。在短短几十年里,抗感染药药典突然向人类提供的可用性可能绕过大自然的经过时间考验的,是死是活进化范式下的提高他们的生存前景不断微生物接二连三。那些以前会的成员被现在可以存活较长时间的帮助下,疫苗和抗生素-助剂与免疫系统对抗感染。实际上,人类的就业这些助剂可以看作举例self-contrived进化免疫防御系统。一旦亚历山大弗莱明爵士的青霉素发现的有效性已经被证明,一系列其他抗生素出土自然来源。其中一些被证明适用于治疗疾病,通常经过化学改性来提高天然化合物的能力,安全或药代动力学资料。在过去50年的大部分时间里,似乎医学得到了强有力的上风在细菌性疾病。一些制药公司和资助机构决定减少抗生素发现努力,看来医生的抗菌阿森纳了。但疾病的性质证明并非如此。在多种抗生素耐药病原体的发病率迅速升级现在提高全球非常严重的问题。这种发展突出了强大的进化能力的细菌种群的选择压力下的抗生素治疗。抗药性问题被视为与革兰氏阴性（例如大肠杆菌）和革兰氏阳性菌（如金黄色葡萄球菌），但目前关注的最后一组的病原体。肺炎链球菌是呼吸道革兰氏阳性病原体，仅在美国一年的40000人死亡负责。现在在许多国家，耐青霉素肺炎链球菌感染的患病率迅速上升。最糟的情况之一是在匈牙利，其中70，从1988-1989年测试的儿童肺炎链球菌菌株对青霉素耐药。细菌已经进化无数花招挫败抗生素的行动, 他们停用抗生素水解，酰化，磷酸化，或者核苷酸化反应；改变抗生素的目标站点或减少细胞内药物浓度降低细胞膜的通透性和或积极抽水细胞的药物