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蛋白质-L-异天冬氨酸甲基转移酶(PIMT)是鼠伤寒沙门氏菌在42°C存活所必需的,且对家禽的致病性有影响。

Protein-L-Isoaspartyl Methyltransferase (PIMT) Is Required for Survival of Typhimurium at 42°C and Contributes to the Virulence in Poultry.

作者信息

Pesingi Pavan K, Kumawat Manoj, Behera Pranatee, Dixit Sunil K, Agarwal Rajesh K, Goswami Tapas K, Mahawar Manish

机构信息

Division of Veterinary Public Health, Indian Veterinary Research Institute Izatnagar, India.

Division of Biochemistry, Indian Veterinary Research Institute Izatnagar, India.

出版信息

Front Microbiol. 2017 Mar 7;8:361. doi: 10.3389/fmicb.2017.00361. eCollection 2017.

Abstract

Poultry birds are asymptomatic reservoir of Typhimurium (. Typhimurium) but act as source of human infection for this bacterium. Inside the poultry, . Typhimurium experiences several stresses, 42°C body temperature of birds is one of them. Proteins are highly susceptible to temperature mediated damage. Conversion of protein bound aspartate (Asp) residues to iso-aspartate (iso-Asp) is one of such modifications that occur at elevated temperature. Iso-Asp formation has been linked to protein inactivation and compromised cellular survival. Protein-L-isoaspartyl methyltransferase (PIMT) can repair iso-Asp back to Asp, thus enhances the cellular survival at elevated temperature. Here, we show that the gene deletion strain of . Typhimurium (Δ mutant strain) is hypersensitive to 42°C . The hypersusceptibility of Δ strain is partially reversed by plasmid based complementation (-complementation) of Δ strain. Following oral inoculation, Δ strain showed defective colonization in poultry caecum, and compromised dissemination to spleen and liver. Interestingly, we have observed three and half folds induction of the PIMT protein following exposure of . Typhimurium to 42°C. Our data suggest a novel role of gene in the survival of . Typhimurium at elevated temperature and virulence.

摘要

家禽是鼠伤寒沙门氏菌(鼠伤寒沙门氏菌)的无症状宿主,但却是这种细菌的人类感染源。在家禽体内,鼠伤寒沙门氏菌会经历多种应激,禽类42°C的体温就是其中之一。蛋白质极易受到温度介导的损伤。蛋白质结合的天冬氨酸(Asp)残基转化为异天冬氨酸(iso-Asp)就是在高温下发生的此类修饰之一。异天冬氨酸的形成与蛋白质失活和细胞存活能力受损有关。蛋白质-L-异天冬氨酰甲基转移酶(PIMT)可以将异天冬氨酸修复成天冬氨酸,从而提高细胞在高温下的存活率。在此,我们表明鼠伤寒沙门氏菌的基因缺失菌株(Δ突变株)对42°C高度敏感。通过基于质粒的Δ菌株互补(-互补),部分逆转了Δ菌株的超敏感性。口服接种后,Δ菌株在家禽盲肠中的定殖存在缺陷,并且向脾脏和肝脏的传播也受到损害。有趣的是,我们观察到鼠伤寒沙门氏菌暴露于42°C后,PIMT蛋白诱导增加了3.5倍。我们的数据表明基因在鼠伤寒沙门氏菌在高温下的存活和毒力方面具有新的作用。

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