The structure of PilA from Acinetobacter baumannii AB5075 suggests a mechanism for functional specialization in Acinetobacter type IV pili
The structure of PilA from Acinetobacter baumannii AB5075 suggests a mechanism for functional specialization in Acinetobacter type IV pili
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DOI：
10.1074/jbc.ra118.005814
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发表时间：
2019-01-04
影响因子：
4.8
通讯作者：
Piepenbrink, Kurt H.
中科院分区：
文献类型：
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作者：
Ronish, Leslie A.;Lillehoj, Erik;Piepenbrink, Kurt H.
IV型皮利（T4 P）是由称为菌毛蛋白的蛋白质亚基组成的细菌附属物，其非共价组装成螺旋纤维。在许多细菌物种中，T4 P对于诸如抽搐运动、自然能力、生物膜或小菌落形成以及宿主细胞粘附等多种过程是必不可少的。编码IV型皮利的基因普遍存在于革兰氏阴性、需氧、无鞭毛和致病性球杆菌鲍氏不动杆菌中，但主要蛋白亚基PilA在氨基酸序列和糖基化模式上存在相当大的变异。在这里，我们报告的X-射线晶体结构的PilA从AB 5075，最近的特点，高毒力的分离，在1.9分辨率，并比较它的同源物从A。鲍曼不动杆菌菌株ACICU和BIDM C57，其是C-末端糖基化的。这些结构比较揭示了PilA（AB 5075）表现出明显的电负性表面化学。为了理解这种表面静电变化的功能后果，我们用来自ACICU、BIDMC 57和AB 5075的不同pilA基因补充pilA敲除菌株。所得的转基因菌株表现出差异抽搐运动性和生物膜形成，同时保持粘附上皮细胞的能力。PilA（AB 5075）和PilA（ACICU）虽然结构相似，但促进不同的特征，分别有利于抽搐运动和生物膜形成。这些结果支持一个模型，其中菌毛静电的差异影响微菌落形成的平衡，这反过来又改变了不动杆菌的运动性和生物膜形成之间的平衡。
Type IV pili (T4P) are bacterial appendages composed of protein subunits, called pilins, noncovalently assembled into helical fibers. T4P are essential, in many bacterial species, for processes as diverse as twitching motility, natural competence, biofilm or microcolony formation, and host cell adhesion. The genes encoding type IV pili are found universally in the Gram-negative, aerobic, nonflagellated, and pathogenic coccobacillus Acinetobacter baumannii, but there is considerable variation in PilA, the major protein subunit, both in amino acid sequence and in glycosylation patterns. Here we report the X-ray crystal structure of PilA from AB5075, a recently characterized, highly virulent isolate, at 1.9 resolution and compare it to homologues from A. baumannii strains ACICU and BIDMC57, which are C-terminally glycosylated. These structural comparisons revealed that PilA(AB5075) exhibits a distinctly electronegative surface chemistry. To understand the functional consequences of this change in surface electrostatics, we complemented a pilA knockout strain with divergent pilA genes from ACICU, BIDMC57, and AB5075. The resulting transgenic strains showed differential twitching motility and biofilm formation while maintaining the ability to adhere to epithelial cells. PilA(AB5075) and PilA(ACICU), although structurally similar, promote different characteristics, favoring twitching motility and biofilm formation, respectively. These results support a model in which differences in pilus electrostatics affect the equilibrium of microcolony formation, which in turn alters the balance between motility and biofilm formation in Acinetobacter.