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Dps 蛋白与脓肿分枝杆菌亚种抗应激条件的能力有关。

Dps protein is related to resistance of Mycobacterium abscessus subsp. massiliense against stressful conditions.

机构信息

Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brazil.

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC (UFABC), Santo André, SP, Brazil.

出版信息

Appl Microbiol Biotechnol. 2020 Jun;104(11):5065-5080. doi: 10.1007/s00253-020-10586-z. Epub 2020 Apr 6.

DOI:10.1007/s00253-020-10586-z
PMID:32253472
Abstract

Mycobacterium abscessus subsp. massiliense (Mycma) belongs to the Mycobacterium abscessus complex and is a rapidly growing non-tuberculous mycobacterium. The chronic pulmonary, skin, and soft tissue infections that it causes may be difficult to treat due to its intrinsic resistance to the commonly used antimicrobial drugs, making it a serious world public health problem. Iron is an essential nutrient for the growth of microorganisms; nonetheless, it can be toxic when in excess. Thus, bacteria require an iron homeostasis mechanism to succeed in different environments. DNA-binding proteins from starved cells (Dps) are miniferritins with the property to act as additional iron storage proteins but also can bind to DNA, protecting it against hydroxyl radical. Annotation of the Mycma genome revealed the gene mycma_03135 with 79% sequential identity when compared to MSMEG_3242 gene from M. smegmatis mc 155, which codifies for a known Dps. Recombinant Dps from M. abscessus (rMaDps) was produced in Escherichia coli, purified in soluble form and shown to form high mass oligomers in solution with ferroxidase activity, DNA binding, and protection against damage. The expression of the mycma_03135 gene was induced during Mycma growth in the presence of hydrogen peroxide (HO). Additionally, the expression of rMaDps by E. coli conferred greater resistance to HO. Thus, this study is the first to identify and characterize a Dps from M. abscessus. KEY POINTS: Mycobacterium abscessus subsp. massiliense express a miniferritin protein (Dps). Mycma Dps binds to DNA and protects against oxidative stress.

摘要

脓肿分枝杆菌亚种(Mycobacterium abscessus subsp. massiliense,Mycma)属于脓肿分枝杆菌复合体,是一种快速生长的非结核分枝杆菌。它引起的慢性肺部、皮肤和软组织感染可能难以治疗,因为它对常用的抗菌药物具有固有耐药性,这使其成为一个严重的全球公共卫生问题。铁是微生物生长所必需的营养物质;然而,当过量时,它可能是有毒的。因此,细菌需要一种铁平衡机制才能在不同的环境中生存。饥饿细胞的 DNA 结合蛋白(Dps)是具有作为额外铁储存蛋白作用的小型 Ferritin,但也可以与 DNA 结合,保护其免受羟基自由基的侵害。Mycma 基因组的注释显示,与 M. smegmatis mc 155 中的 MSMEG_3242 基因相比,mycma_03135 基因具有 79%的序列同一性,该基因编码一种已知的 Dps。脓肿分枝杆菌的重组 Dps(rMaDps)在大肠杆菌中表达,以可溶形式纯化,并显示出在溶液中形成高质量寡聚物的能力,具有亚铁氧化酶活性、DNA 结合能力和对损伤的保护作用。Mycma 在过氧化氢(HO)存在下生长时,mycma_03135 基因的表达被诱导。此外,大肠杆菌中 rMaDps 的表达赋予了对 HO 的更高抗性。因此,本研究首次鉴定和表征了脓肿分枝杆菌的 Dps。关键点:脓肿分枝杆菌亚种表达一种小型 Ferritin 蛋白(Dps)。Mycma Dps 结合 DNA 并抵抗氧化应激。

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