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细菌被膜研究的新发现

细菌研究领域又有重大发现(图)

生物被膜是指细菌粘附于接触表面,分泌多糖基质、纤维蛋白、脂质蛋白等,将其自身包绕其中而形成的大量细菌聚集膜样物。

在特定的条件下,细菌可以形成生物被膜,包被有生物被膜的细菌称为被膜菌。被膜菌无论其形态结构、生理生化特性、致病性还是对环境因子的敏感性等都与浮游细菌有显著的不同,尤其对抗生素和宿主免疫系统具有很强的抵抗力,从而导致严重的临床问题,引起许多慢性和难治性感染疾病的反复发作。

许多医疗设备都很容易被微生物病原体生物被膜所粘附,其极难清除,会对人类免疫系统和健康产生重大影响。现在爱荷华州大学的生物学家们发现一种细菌其实可以形成两种不同的生物被膜。

而在此之前,所有的科学家们都认为一种细菌只产生一种生物被膜,但是爱荷华州大学的生物学家Soll和他的研究小组发现有害病原体白念珠菌能形成两种生物被膜,一个是广泛认知具有致病作用的,而另一个是用于细菌繁殖的。该论文发表在最近的《Plos Biology》上,这在细菌病原体生物被膜研究领域上是一个全新的发现。

Soll和他的研究小组还首次发现,大约有90%的细菌的致病性生物被膜无法穿透人体中的抗菌介质、抗体或白细胞,这些细菌大多不能形成繁殖性生物被膜。但有大约10%能形成繁殖性生物被膜的细菌,具有高渗透、高穿透的能力,能引发疾病。

尽管在显微镜下这两种不同的生物被膜形态非常相似,但它们的功能完全不同。其中致病性生物被膜有很强的抗性能力,而繁殖型生物被膜没有任何抗性,这也为我们未来开发新型药物提供了新思路。

原文摘要:

Alternative Mating Type Configurations (a/α versus a/a or α/α) of Candida albicans Result in Alternative Biofilms Regulated by Different Pathways

Similar multicellular structures can evolve within the same organism that may have different evolutionary histories, be controlled by different regulatory pathways, and play similar but nonidentical roles. In the human fungal pathogen Candida albicans, a quite extraordinary example of this has occurred. Depending upon the configuration of the mating type locus (a/α versus a/aor α/α), C. albicans forms alternative biofilms that appear similar morphologically, but exhibit dramatically different characteristics and are regulated by distinctly different signal transduction pathways. Biofilms formed by a/α cells are impermeable to molecules in the size range of 300 Da to 140 kDa, are poorly penetrated by human polymorphonuclear leukocytes (PMNs), and are resistant to antifungals. In contrast, a/a or α/α biofilms are permeable to molecules in this size range, are readily penetrated by PMNs, and are susceptible to antifungals. By mutational analyses, a/α biofilms are demonstrated to be regulated by the Ras1/cAMP pathway that includes Ras1→Cdc35→cAMP(Pde2—|)→Tpk2(Tpk1)→Efg1→Tec1→Bcr1, and a/a biofilms by the MAP kinase pathway that includes Mfα→Ste2→ (Ste4, Ste18, Cag1)→Ste11→Hst7→Cek2(Cek1)→Tec1. These observations suggest the hypothesis that while the upstream portion of the newly evolved pathway regulating a/a and α/α cell biofilms was derived intact from the upstream portion of the conserved pheromone-regulated pathway for mating, the downstream portion was derived through modification of the downstream portion of the conserved pathway for a/α biofilm formation. C. albicans therefore forms two alternative biofilms depending upon mating configuration.

 

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