质粒介导重排子的发现、结构和功能

Discovery, structure and function of plasmid mediated shufflon

摘要:

细菌耐药性已成为全球关注的重大公共卫生问题。接合转移是耐药质粒快速传播的重要方式，其中Ⅳ型菌毛在此过程中发挥着重要的作用。Ⅳ型菌毛具有黏附作用，能够使细菌黏附在宿主细胞和其他介质表面，帮助细菌形成生物被膜、细菌聚集体和微菌落，是细菌在液体中接合转移的重要因素。PilV蛋白是R64质粒Ⅳ型菌毛尖端黏附素，可以识别细菌细胞膜上的脂多糖(lipopolysaccharide, LPS)。重排子(shufflon)结构是多重DNA倒位系统，可使PilV蛋白多样化，进而影响细菌液体接合转移过程中的受体菌识别和接合转移频率。重排子结构最先发现存在于IncI1质粒R64，后陆续在IncI2、IncK、IncZ质粒以及伤寒沙门氏菌致病岛中被发现，其主要由A、B、C、D这4个片段及特异性重组位点sfx组成，受其下游重组酶基因rci的调控，不同质粒的重排子结构存在一定的差异。近期备受关注的可转移多黏菌素耐药基因mcr-1主要位于IncI2型质粒上，重排子可能是其快速传播的原因之一。本文综述了质粒介导重排子的发现、结构、功能和流行，期望基于对重排子更全面深入地了解，能够为耐药质粒的传播机制和控制策略研究提供理论基础。

Abstract:

Antimicrobial resistance has become a major public health issue of global concern. Conjugation is an important way for fast spreading drug-resistant plasmids, during which the type Ⅳ pili plays an important role. Type Ⅳ pili can adhere on the surfaces of host cell and other medium, facilitating formation of bacterial biofilms, bacterial aggregations and microcolonies, and is also a critical factor in liquid conjugation. PilV is an adhesin-type protein found on the tip of type Ⅳ pili encoded by plasmid R64, and can recognize the lipopolysaccharid (LPS) molecules that locate on bacterial membrane. The shufflon is a clustered inversion region that diversifies the PilV protein, which consequently affects the recipient recognition and conjugation frequency in liquid mating. The shufflon was firstly discovered on an IncI1 plasmid R64 and has been identified subsequently in plasmids IncI2, IncK and IncZ, as well as the pathogenicity island of Salmonella typhi. The shufflon consists of four segments including A, B, C, and D, and a specific recombination site named sfx. The shufflon is regulated by its downstream-located recombinase-encoding gene rci, and different rearrangements of the shufflon region in different plasmids were observed. Mobile colistin resistance gene mcr-1, which has attracted substantial attentions recently, is mainly located in IncI2 plasmid. The shufflon may be one of the contributors to fast spread of mcr-1. Herein, we reviewed the discovery, structure, function and prevalence of plasmid mediated shufflon, aiming to provide a theoretical basis on transmission mechanism and control strategy of drug-resistant plasmids.