McDonald Nathan D, Lubin Jean-Bernard, Chowdhury Nityananda, Boyd E Fidelma
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA
mBio. 2016 Apr 12;7(2):e02237-15. doi: 10.1128/mBio.02237-15.
A major challenge facing bacterial intestinal pathogens is competition for nutrient sources with the host microbiota.Vibrio cholerae is an intestinal pathogen that causes cholera, which affects millions each year; however, our knowledge of its nutritional requirements in the intestinal milieu is limited. In this study, we demonstrated that V. cholerae can grow efficiently on intestinal mucus and its component sialic acids and that a tripartite ATP-independent periplasmic SiaPQM strain, transporter-deficient mutant NC1777, was attenuated for colonization using a streptomycin-pretreated adult mouse model. In in vivo competition assays, NC1777 was significantly outcompeted for up to 3 days postinfection. NC1777 was also significantly outcompeted in in vitro competition assays in M9 minimal medium supplemented with intestinal mucus, indicating that sialic acid uptake is essential for fitness. Phylogenetic analyses demonstrated that the ability to utilize sialic acid was distributed among 452 bacterial species from eight phyla. The majority of species belonged to four phyla, Actinobacteria (members of Actinobacillus, Corynebacterium, Mycoplasma, and Streptomyces), Bacteroidetes (mainly Bacteroides, Capnocytophaga, and Prevotella), Firmicutes (members of Streptococcus, Staphylococcus, Clostridium, and Lactobacillus), and Proteobacteria (including Escherichia, Shigella, Salmonella, Citrobacter, Haemophilus, Klebsiella, Pasteurella, Photobacterium, Vibrio, and Yersinia species), mostly commensals and/or pathogens. Overall, our data demonstrate that the ability to take up host-derived sugars and sialic acid specifically allows V. cholerae a competitive advantage in intestinal colonization and that this is a trait that is sporadic in its occurrence and phylogenetic distribution and ancestral in some genera but horizontally acquired in others.
Sialic acids are nine carbon amino sugars that are abundant on all mucous surfaces. The deadly human pathogen Vibrio cholerae contains the genes required for scavenging, transport, and catabolism of sialic acid. We determined that the V. cholerae SiaPQM transporter is essential for sialic acid transport and that this trait allows the bacterium to outcompete noncatabolizers in vivo. We also showed that the ability to take up and catabolize sialic acid is prevalent among both commensals and pathogens that colonize the oral cavity and the respiratory, intestinal, and urogenital tracts. Phylogenetic analysis determined that the sialic acid catabolism phenotype is ancestral in some genera such as Yersinia, Streptococcus, and Staphylococcus and is acquired by horizontal gene transfer in others such as Vibrio, Aeromonas, and Klebsiella. The data demonstrate that this trait has evolved multiple times in different lineages, indicating the importance of specialized metabolism to niche expansion.
肠道细菌病原体面临的一个主要挑战是与宿主微生物群争夺营养源。霍乱弧菌是一种引起霍乱的肠道病原体，每年影响数百万人；然而，我们对其在肠道环境中的营养需求了解有限。在本研究中，我们证明霍乱弧菌能够在肠道黏液及其成分唾液酸上高效生长，并且使用链霉素预处理的成年小鼠模型，一个不依赖ATP的周质唾液酸转运蛋白SiaPQM缺失的突变株NC1777在定殖方面减弱。在体内竞争试验中，感染后长达3天，NC1777明显处于劣势。在补充了肠道黏液的M9基本培养基的体外竞争试验中，NC1777也明显处于劣势，这表明摄取唾液酸对适应性至关重要。系统发育分析表明，利用唾液酸的能力分布在来自八个门的452种细菌中。大多数物种属于四个门，放线菌门（放线杆菌属、棒状杆菌属、支原体属和链霉菌属的成员）、拟杆菌门（主要是拟杆菌属、嗜二氧化碳噬纤维菌属和普雷沃菌属）、厚壁菌门（链球菌属、葡萄球菌属、梭菌属和乳杆菌属的成员）和变形菌门（包括大肠杆菌、志贺氏菌、沙门氏菌、柠檬酸杆菌、嗜血杆菌、克雷伯氏菌、巴斯德氏菌、发光杆菌属、弧菌属和耶尔森氏菌属的物种），大多是共生菌和/或病原体。总体而言，我们的数据表明，摄取宿主来源的糖和唾液酸的能力使霍乱弧菌在肠道定殖中具有竞争优势，并且这是一种在其发生和系统发育分布中呈散发性的特征，在一些属中是祖传的，但在其他属中是水平获得的。
唾液酸是在所有黏液表面都大量存在的九碳氨基糖。致命的人类病原体霍乱弧菌含有清除、转运和分解代谢唾液酸所需的基因。我们确定霍乱弧菌的SiaPQM转运蛋白对唾液酸转运至关重要，并且这一特征使该细菌在体内能够胜过非分解代谢者。我们还表明，摄取和分解代谢唾液酸的能力在定殖于口腔、呼吸道、肠道和泌尿生殖道的共生菌和病原体中普遍存在。系统发育分析确定，唾液酸分解代谢表型在一些属如耶尔森氏菌属、链球菌属和葡萄球菌属中是祖传的，而在其他属如弧菌属、气单胞菌属和克雷伯氏菌属中是通过水平基因转移获得的。数据表明，这一特征在不同谱系中已经多次进化，表明特殊代谢对生态位扩展的重要性。
