Noel Hannah R, Winkelman Jonathan D, Palmer Lauren D
Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, IL, USA.
Trestle LLC, Milwaukee, WI, USA.
bioRxiv. 2025 Jul 15:2025.07.02.662759. doi: 10.1101/2025.07.02.662759.
is a pathogen of concern and a leading cause of multidrug-resistant healthcare-associated infections. The outer membrane is a barrier to antimicrobials and host defenses but must also allow essential nutrients to permeate. Here, we investigate the functional importance of the putative DcaP-family outer membrane porins, which include a proposed vaccine target in . All genomes surveyed encode multiple DcaP family porins, which we classify in four classes based on protein sequence phylogeny (DcaP1-4). DcaP proteins encoded by species in other genera could not be mapped to these DcaP classes and phylogenetic analysis suggests DcaP1-4 proteins diversified within . Phenotypic array assays and additional experiments show that DcaP3 was necessary for growth on multiple di- and tri-carboxylic acids as sole carbon sources, including citric acid and tricarballylic acid. Finally, a mutant lacking all DcaP proteins was attenuated in the liver and spleen in a mouse model of bloodstream infection and complemented by expression of DcaP3. These findings provide insight on how acquires nutrients through the outer membrane barrier and show DcaP3 is important during infection in specific host niches, validating its potential as a therapeutic target.
是一种受关注的病原体，也是耐多药医疗保健相关感染的主要原因。外膜是抗菌剂和宿主防御的屏障，但也必须允许必需营养物质渗透。在此，我们研究了假定的DcaP家族外膜孔蛋白的功能重要性，其中包括在 中提出的疫苗靶点。所有被调查的 基因组都编码多种DcaP家族孔蛋白，我们根据蛋白质序列系统发育将其分为四类（DcaP1 - 4）。其他属物种编码的DcaP蛋白无法映射到这些DcaP类别，系统发育分析表明DcaP1 - 4蛋白在 内发生了多样化。表型阵列分析和其他实验表明，DcaP3对于以多种二羧酸和三羧酸作为唯一碳源生长是必需的，包括柠檬酸和三羟基三羧酸。最后，在血流感染小鼠模型中，缺乏所有DcaP蛋白的突变体在肝脏和脾脏中减毒，并通过DcaP3的表达得到补充。这些发现为 如何通过外膜屏障获取营养提供了见解，并表明DcaP3在特定宿主生态位感染期间很重要，验证了其作为治疗靶点的潜力。
