AbaM Regulates Quorum Sensing, Biofilm Formation, and Virulence in Acinetobacter baumannii.
AbaM Regulates Quorum Sensing, Biofilm Formation, and Virulence in Acinetobacter baumannii.
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AbaM调节鲍氏不动杆菌的群体感应、生物膜形成和毒力。
DOI：
10.1128/jb.00635-20
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发表时间：
2021-03-23
影响因子：
3.2
通讯作者：
Williams P
中科院分区：
文献类型：
--
作者：
López-Martín M;Dubern JF;Alexander MR;Williams P
鲍曼不动杆菌是一种具有多重耐药性的病原体，对全球卫生保健具有重要意义。了解不动杆菌毒力基因调控有助于开发新的抗感染策略。鲍曼不动杆菌具有一个单一的分歧luxR/luxRI型群体感应（QS）基因座abaR/abaI。该基因座还包含位于abaR和abaI之间的第三个基因，我们称之为abaM，其编码已知调节其他β-和γ-变形菌中N-酰基高丝氨酸内酯（阿勒）依赖性QS的RsaM蛋白家族的未表征成员。在这里，我们表明通过在A.鲍曼不动杆菌菌株AB 5075导致N-（3-羟基十二烷酰基）-1-高丝氨酸内酯的产生增加，并增强表面运动性和生物膜形成。与野生型和abaI：：T26突变体相反，abaM：：T26突变体的毒力在大蜡螟感染模型中完全减弱。转录组学分析abaM：：T26突变体显示，AbaM差异调节至少76个基因，包括csu菌毛操纵子和acinetin 505脂肽生物合成操纵子，参与表面粘附，生物膜形成和毒力。野生型abaM：：T26和abaI：：T26转录组的比较表明，AbaM调节包括csu操纵子在内的21%的QS调节子。此外，QS基因（abaI和abaR）在abaM：：T26突变体中上调最多。A.基于鲍曼不动杆菌lux的abaM报告基因融合揭示abaM表达受QS正调控，但负自调控。总体而言，本研究中提供的数据表明，AbaM在调节A.鲍曼不动杆菌QS、毒力、表面运动性和生物膜形成。重要性鲍曼不动杆菌是一种具有多重耐药性的病原体，对全球卫生保健具有重要意义。了解不动杆菌毒力基因调控有助于开发新的抗感染策略。以.在鲍曼不动杆菌中，编码N-酰基高丝氨酸（阿勒）内酯依赖性群体感应系统（QS）的受体和合酶组分的abaR和abaI基因被abaM分开。在这里，我们表明，虽然abaM的突变增加阿勒生产，表面运动，和生物膜的发展，它导致毒力的衰减。AbaM被发现控制QS依赖性和QS非依赖性基因。这项工作的意义在于鉴定AbaM，已知控制植物病原体毒力的RsaM直系同源物，作为人类病原体毒力的调节剂。
Acinetobacter baumannii is a multiantibiotic-resistant pathogen of global health care importance. Understanding Acinetobacter virulence gene regulation could aid the development of novel anti-infective strategies. Acinetobacter baumannii possesses a single divergent luxR/luxRI-type quorum-sensing (QS) locus named abaR/abaI. This locus also contains a third gene located between abaR and abaI, which we term abaM, that codes for an uncharacterized member of the RsaM protein family known to regulate N-acylhomoserine lactone (AHL)-dependent QS in other beta- and gammaproteobacteria. Here, we show that disruption of abaM via a T26 insertion in A. baumannii strain AB5075 resulted in increased production of N-(3-hydroxydodecanoyl)-l-homoserine lactone and enhanced surface motility and biofilm formation. In contrast to the wild type and the abaI::T26 mutant, the virulence of the abaM::T26 mutant was completely attenuated in a Galleria mellonella infection model. Transcriptomic analysis of the abaM::T26 mutant revealed that AbaM differentially regulates at least 76 genes, including the csu pilus operon and the acinetin 505 lipopeptide biosynthetic operon, that are involved in surface adherence, biofilm formation and virulence. A comparison of the wild type, abaM::T26 and abaI::T26 transcriptomes, indicates that AbaM regulates ∼21% of the QS regulon including the csu operon. Moreover, the QS genes (abaI and abaR) were among the most upregulated in the abaM::T26 mutant. A. baumannii lux-based abaM reporter gene fusions revealed that abaM expression is positively regulated by QS but negatively autoregulated. Overall, the data presented in this work demonstrates that AbaM plays a central role in regulating A. baumannii QS, virulence, surface motility, and biofilm formation. IMPORTANCE Acinetobacter baumannii is a multiantibiotic-resistant pathogen of global health care importance. Understanding Acinetobacter virulence gene regulation could aid the development of novel anti-infective strategies. In A. baumannii, the abaR and abaI genes that code for the receptor and synthase components of an N-acylhomoserine (AHL) lactone-dependent quorum sensing system (QS) are separated by abaM. Here, we show that although mutation of abaM increased AHL production, surface motility, and biofilm development, it resulted in the attenuation of virulence. AbaM was found to control both QS-dependent and QS-independent genes. The significance of this work lies in the identification of AbaM, an RsaM ortholog known to control virulence in plant pathogens, as a modulator of virulence in a human pathogen.