新型抗生素不杀死细菌
研究人员发现了一种新型抗生素，它不会杀死细菌，但可阻止细菌合成内毒素。http://www.techreviewchina.com/upload/article/picture/1349337791269.JPG鲍氏不动杆菌（图片来源：Wikipedia）研究人员发现了一种新型抗生素，可以有效地治疗耐药性细菌感染，因为它无需杀死细菌就可以让它们缴械。研究被发表在10月2号的mBio®，这是美国微生物协会（American Society for Microbiology）主办的可免费阅读的学术杂志。
“传统上，人们希望找到可以快速杀死细菌的抗生素，但是我们找到了一种新的抗生素类型，它不会杀死不动杆菌属（Acientobacter），但却可以完全预防这些细菌让寄主发炎。”加州大学洛杉矶分校医学中心的Brad Spellberg说。他也是David Geffen医学院，同时也是参与这项研究的人员之一。
现在急需治疗鲍氏不动杆菌（Acinetobacter baumannii）的新药。鲍氏不动杆菌经常通过开放伤口、呼吸管或导尿管感染医院的病人和免疫缺陷的个体。这种病菌可以导致致死性的血液感染。鲍氏不动杆菌的菌株已获得耐受很多抗生素的能力，有些菌株甚至可以抵抗所有FDA批准的抗生素，所以无药可治。
Spellberg和他的同事利用实验室小鼠发现，一种抗生素可以降低鲍氏不动杆菌的致死率，但是它不会杀死细菌，而是抑制细菌产生的毒素。
“我们发现一些可以产生感染并让宿主迅速死亡的菌株，它们在生长时可以产生脂多糖（也叫LPS或内毒素）。菌株产生的内毒素越多，毒性就越大。”Spellberg说。这项研究为研究人员找到了一种新的治疗目标：细菌在体内产生的内毒素。如果用一个名为LpxC-1的小分子阻止内毒素的合成，就可以防止感染小鼠发病。Spellberg说，LpxC-1不像传统的抗生素，它不会杀死细菌，而只是停止内毒素的生产和身体的炎症免疫反应，后者是病情严重的病人死亡的真正原因。
Spellberg表示，他用的是研究人员很少采用的治疗感染的方向，但这却可以找到有效的药物。论文作者也写道，研究结果彰显了针对高度耐药菌寻找新的、生理相关的方法筛选潜在抗生素的重要性。LpxC-1这样抑制而非杀灭细菌的分子不会通过传统的抗生素筛选。因为传统抗生素筛选看得是抗生素能否有效地杀死细菌。
阿尔伯特•爱因斯坦医学院（Albert Einstein College of Medicine）的Liise-anne Pirofski 是这篇发表在mBio®上论文的审稿人。她说，中和毒性因子是治疗感染的一种替代方法，很有前途。“现在，越来越多的治疗感染疾病的方法是控制宿主的炎症反应，而不是简单地杀死细菌，”Pirofski说，“这次的研究是对这种方法的一个漂亮而重要的验证—至少对小鼠来说如此。”
本文编译自美国微生物协会的新闻稿。
（翻译 杨清合）
相关论文：
Lin Lin, Brandon Tan, Paul Pantapalangkoor, Tiffany Ho, Beverlie Baquir, Andrew Tomaras, Justin I. Montgomery, Usa Reilly, Elsa G. Barbacci, Kristine Hujer, Robert A. Bonomo, Lucia Fernandez, Robert E. W. Hancock, Mark D. Adams, Samuel W. French, Virgil S. Buslon, and Brad Spellberg.
Inhibition of LpxC Protects Mice from Resistant Acinetobacter baumannii by Modulating Inflammation and Enhancing Phagocytosis. mBio, October 2012; DOI:10.1128/mBio.00312-12
New antibiotic cures disease by disarming pathogens, not killing them
CONTACT:Jim Sliwa
jsliwa@asmusa.org
WASHINGTON, DC – October 2, 2012 – A new type of antibiotic can effectively treat an antibiotic-resistant infection by disarming instead of killing the bacteria that cause it. Researchers report their findings in the October 2 issue of mBio®, the online open-access journal of the American Society for Microbiology.
“Traditionally, people have tried to find antibiotics that rapidly kill bacteria. But we found a new class of antibiotics which has no ability to kill Acinetobacter that can still protect, not by killing the bug, but by completely preventing it from turning on host inflammation,” says Brad Spellberg of the UCLA Medical Center and David Geffen School of Medicine, a researcher on the study.
New drugs are badly needed for treating infections with the bacterium Acinetobacter baumannii, a pathogen that most often strikes hospital patients and immune- compromised individuals through open wounds, breathing tubes, or catheters. The bacterium can cause potentially lethal bloodstream infections. Strains of A. baumannii have acquired resistance to a wide range of antibiotics, and some are resistant to every FDA-approved antibiotic, making them untreatable.
Spelling and his colleagues found that in laboratory mice it was possible to mitigate the potentially lethal effects of the bacterium by blocking one of its toxic products rather than killing it.
“We found that strains that caused the rapidly lethal infections shed lipopolysaccharide while growing. The more endotoxin shed, the more virulent the strain was,” says Spellberg. This pinpointed a new therapy target for the researchers: the endotoxin these bacteria shed in the body.
Blocking the synthesis of the endotoxin with a small molecule called LpxC-1 prevented infected mice from getting sick. Unlike traditional antibiotics, Spellberg says, LpxC-1 doesn’t kill the bacteria, it just shuts down the manufacture of the endotoxin and stops the body from mounting the inflammatory immune response to it that is the actual cause of death in seriously ill patients.
Spellberg says this is a direction few researchers have taken when exploring ways to treat infections but that it could make the difference in finding an effective drug. The results also highlight how important it is to find new, physiologically relevant ways of screening potential antibiotics for pathogens with a high degree of resistance, write the authors. Molecules like LpxC-1 that inhibit rather than kill bacteria wouldn’t pass muster with traditional antibiotic screens that are based on killing effectiveness.
Liise-anne Pirofski of the Albert Einstein College of Medicine and a reviewer of the study for mBio® says neutralizing virulence factors is showing a lot of promise as an alternative route for treating infections. “There’s a growing movement in infectious disease therapy to control the host inflammation response in treatment rather than just ‘murdering’ the organism,” says Pirofski. “This is a very elegant and important validation that this approach can work – at least in mice.”
A copy of journal article can be found online at http://mbio.asm.org/content/3/5/e00312-12
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