2012年8月17日 訊 /生物谷BIOON/ --一項(xiàng)新研究可能解釋著當(dāng)細(xì)菌進(jìn)入人們的血液之后,，為什么每年成百上千名美國(guó)人患病，上萬(wàn)名美國(guó)人死亡,。它也提示著為什么有些血液感染即便在接受最為強(qiáng)效的抗生素治療之后，也能存活下來(lái),。相關(guān)研究論文發(fā)表在Journal of Infectious Diseases期刊上,。
在這篇論文中，來(lái)自美國(guó)密歇根大學(xué)的一個(gè)研究小組證實(shí)細(xì)菌能夠在短時(shí)間內(nèi)形成抗生素耐受性的菌落,，即便是在諸如血液的流動(dòng)液體中,，也是如此。
研究利用一種特殊的被稱作生物反應(yīng)器的設(shè)備來(lái)作出這種發(fā)現(xiàn)的：這種設(shè)備模擬血液流動(dòng)的湍動(dòng)和力量,，加入一種常見(jiàn)性導(dǎo)致血液感染的細(xì)菌到該設(shè)備中,。在短短兩個(gè)小時(shí)內(nèi),，在這種流動(dòng)液體中形成的細(xì)菌菌落(bacterial clump)是由10到20個(gè)細(xì)菌組成的，并且這種時(shí)間大約與它讓病人出現(xiàn)感染所花的時(shí)間一樣,。
研究人員也證實(shí)這些菌落只有當(dāng)某些粘性糖分子在細(xì)菌表面上存在時(shí)才能形成,。即便當(dāng)兩種不同類型的抗生素加入時(shí)，這些菌落也能持續(xù)存在,，這提示著細(xì)菌粘連在一起讓漂浮的細(xì)胞免受這些藥物的作用,。
當(dāng)研究人員把這些菌落注射到小鼠體內(nèi)時(shí)，即便在血液中多次游動(dòng)時(shí),，它們也能保持完整,。這些菌落---大約紅細(xì)胞的大小---似乎能夠在流動(dòng)液體的過(guò)濾中存活下來(lái)。這種過(guò)濾正常條件下是在最小血管中發(fā)生的,，保護(hù)身體免受入侵物感染,。
在這項(xiàng)研究中，研究人員加入液體培養(yǎng)基到生物反應(yīng)器中,，然后仔細(xì)地控制轉(zhuǎn)頭的旋轉(zhuǎn)以便在液體中產(chǎn)生類似于血液的渦流,。他們隨后加入肺炎克雷伯氏菌(Klebsiella pneumoniae)到生物反應(yīng)器當(dāng)中。他們測(cè)試了兩種醫(yī)生們經(jīng)常用來(lái)治療敗血癥的抗生素：頭孢曲松(ceftriaxone)和環(huán)丙沙星(ciprofloxacin),。沒(méi)有一種抗生素能夠有效地殺死細(xì)菌,。(生物谷Bioon.com)
本文編譯自Danger in the blood: Scientists show how antibiotic-resisting bacterial infections may form
doi: 10.1093/infdis/jis397
PMC:
PMID:
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.
