2012年8月17日 讯 /生物谷BIOON/ --一项新研究可能解释着当细菌进入人们的血液之后，为什么每年成百上千名美国人患病，上万名美国人死亡。它也提示着为什么有些血液感染即便在接受最为强效的抗生素治疗之后，也能存活下来。相关研究论文发表在Journal of Infectious Diseases期刊上。
在这篇论文中，来自美国密歇根大学的一个研究小组证实细菌能够在短时间内形成抗生素耐受性的菌落，即便是在诸如血液的流动液体中，也是如此。
研究利用一种特殊的被称作生物反应器的设备来作出这种发现的：这种设备模拟血液流动的湍动和力量，加入一种常见性导致血液感染的细菌到该设备中。在短短两个小时内，在这种流动液体中形成的细菌菌落(bacterial clump)是由10到20个细菌组成的，并且这种时间大约与它让病人出现感染所花的时间一样。
研究人员也证实这些菌落只有当某些粘性糖分子在细菌表面上存在时才能形成。即便当两种不同类型的抗生素加入时，这些菌落也能持续存在，这提示着细菌粘连在一起让漂浮的细胞免受这些药物的作用。
当研究人员把这些菌落注射到小鼠体内时，即便在血液中多次游动时，它们也能保持完整。这些菌落---大约红细胞的大小---似乎能够在流动液体的过滤中存活下来。这种过滤正常条件下是在最小血管中发生的，保护身体免受入侵物感染。
在这项研究中，研究人员加入液体培养基到生物反应器中，然后仔细地控制转头的旋转以便在液体中产生类似于血液的涡流。他们随后加入肺炎克雷伯氏菌(Klebsiella pneumoniae)到生物反应器当中。他们测试了两种医生们经常用来治疗败血症的抗生素：头孢曲松(ceftriaxone)和环丙沙星(ciprofloxacin)。没有一种抗生素能够有效地杀死细菌。(生物谷Bioon.com)
本文编译自Danger in the blood: Scientists show how antibiotic-resisting bacterial infections may form
doi: 10.1093/infdis/jis397
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Multicellularity and Antibiotic Resistance in Klebsiella pneumoniae Grown Under Bloodstream-Mimicking Fluid Dynamic Conditions
Margaret M. Thornton1, Hangyul M. Chung-Esaki1,a, Charlene B. Irvin1, David M. Bortz3, Michael J. Solomon2 and John G. Younger1
Background. While the importance of fluid dynamical conditions is well recognized in the growth of biofilms, their role during bacteremia is unknown. We examined the impact of physiological fluid shear forces on the development of multicellular aggregates of Klebsiella pneumoniae. Methods. Wild-type and O-antigen or capsular mutants of K. pneumoniae were grown as broth culture in a Taylor-Couette flow cell configured to provide continuous shear forces comparable to those encountered in the human arterial circulation (ie, on the order of 1.0 Pa). The size distribution and antibiotic resistance of aggregates formed in this apparatus were determined, as was their ability to persist in the bloodstream of mice following intravenous injection. Results. Unlike growth in shaking flasks, bacteria grown in the test apparatus readily formed aggregates, a phenotype largely absent in capsular mutants and to a lesser degree in O-antigen mutants. Aggregates were found to persist in the bloodstream of mice. Importantly, organisms grown under physiological shear were found to have an antibiotic resistance phenotype intermediate between that of fully planktonic and biofilm states. Conclusions. When grown under intravascular-magnitude fluid dynamic conditions, K. pneumoniae spontaneously develops into multicellular aggregates that are capable of persisting in the circulation and exhibit increased antibiotic resistance.
