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临床肺炎克雷伯菌的多种多糖产生能力和生物膜形成能力

Diverse polysaccharide production and biofilm formation abilities of clinical Klebsiella pneumoniae.

作者信息

Fleeman Renee, Beckman Robert, Cella Elenora, Azarian Taj, Rendueles Olaya

机构信息

University of Central Florida.

Center of Integrative Biology.

出版信息

Res Sq. 2024 Aug 9:rs.3.rs-4630973. doi: 10.21203/rs.3.rs-4630973/v1.

Abstract

infections have become a growing threat for human health. The lack of understanding of the relationship between antibiotic resistance, mucoviscosity, and biofilm formation in clinical isolates impedes our abilities to effectively predict K. infection outcomes. These traits are also associated with fitness in natural populations and more specifically within a host. The Multidrug-Resistant Organism Repository and Surveillance Network offers a unique opportunity into the genetic and phenotypic variabilities in the isolates encountered in the clinics today. To this end, we compared the genetic profiles of these isolates with the phenotypic biofilm formation abilities, percent mucoviscosity, and growth rates. We found most isolates formed limited biofilm, although a select group of isolates could form extremely robust biofilms. Variation in biofilm formation could not be explained by difference in growth rate, suggesting specific genetic and physical determinants. Interestingly, the most mucoid strains in the populations were lacking the genetic element regulating the mucoid phenotype and three of these isolates were able to form robust biofilms. There was a significant phenotype-genotype correlation with decreased biofilm formation and an insertion sequence in the transcriptional activator of the type III fimbrial system. Finally, confocal microscopy highlighted the structural and spatial heterogeneity of biofilm among the most robust biofilm formers not detected by traditional methods. The combination of phenotypic, genomic and image analyses allowed us to reveal an unexpected phenotypic diversity and an intricate relation between growth, mucoviscosity and specific virulence-associated genetic determinants.

摘要

感染已对人类健康构成日益严重的威胁。对临床分离株中抗生素耐药性、黏液黏稠度和生物膜形成之间关系的认识不足,阻碍了我们有效预测肺炎克雷伯菌感染结果的能力。这些特性也与自然种群中的适应性相关,更具体地说是与宿主体内的适应性相关。多药耐药生物库与监测网络为了解当今临床中遇到的肺炎克雷伯菌分离株的遗传和表型变异性提供了独特的机会。为此,我们将这些分离株的基因图谱与表型生物膜形成能力、黏液黏稠度百分比和生长速率进行了比较。我们发现大多数分离株形成的生物膜有限,尽管有一组特定的分离株能够形成极其坚固的生物膜。生物膜形成的差异无法用生长速率的差异来解释,这表明存在特定的遗传和物理决定因素。有趣的是,群体中最黏液样的菌株缺乏调节黏液样表型的遗传元件,其中三个分离株能够形成坚固的生物膜。生物膜形成减少与III型菌毛系统转录激活因子中的插入序列之间存在显著的表型-基因型相关性。最后,共聚焦显微镜突出了传统方法未检测到的最坚固生物膜形成者中生物膜的结构和空间异质性。表型、基因组和图像分析的结合使我们能够揭示出意想不到的表型多样性以及生长、黏液黏稠度和特定毒力相关遗传决定因素之间的复杂关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a82/11326372/a26b72516a19/nihpp-rs4630973v1-f0001.jpg

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