One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Pseudomonas aeruginosa Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by P. aeruginosa to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides N-acetyl-galactosamine and N-acetylglucosamine are required for P. aeruginosa killing of Caenorhabditis elegans We also found that the defective adhesion of P. aeruginosa to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in C. elegans lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as P. aeruginosa that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides.IMPORTANCE One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of Pseudomonas aeruginosa to colonize the intestine and ultimately cause death in Caenorhabditis elegans We also demonstrate that monosaccharides alter the ability of bacteria to bind to both Caenorhabditis elegans intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.

中文翻译：

---

宿主粘蛋白被铜绿假单胞菌利用来提供成功感染所需的单糖。

粘膜屏障的主要功能之一，发现衬里上皮细胞，是作为抵御微生物病原体的第一道防线。粘液的主要结构成分是高度糖基化的蛋白质，称为粘蛋白。粘蛋白是先天免疫系统的关键组成部分，因为它们有助于清除病原体并可以降低病原体的毒力。最近也有报道称，单个粘蛋白和衍生聚糖可以减弱人类病原体铜绿假单胞菌的毒力在这里，我们显示的数据表明粘蛋白不仅在宿主防御中发挥作用，而且它们也可以被铜绿假单胞菌破坏以导致疾病。我们发现粘蛋白 MUL-1 和粘蛋白衍生的单糖 N-乙酰半乳糖胺和 N-乙酰葡糖胺是 P. 铜绿假单胞菌杀死秀丽隐杆线虫 我们还发现铜绿假单胞菌对人肺泡上皮细胞的粘附缺陷，缺乏粘蛋白 MUC1，可以通过添加单个单糖来逆转。本研究中鉴定的单糖存在于广泛的生物体中，它们充当细菌发病机制所需的宿主因子。虽然秀丽隐杆线虫中的粘蛋白缺乏唾液酸帽，这使得它们的单糖很容易获得，但它们在其他物种中是有帽的。缺乏唾液酸酶的铜绿假单胞菌等病原体可能依赖其他细菌的酶来利用粘蛋白衍生的单糖。重要意义粘膜上皮组织的第一道防线之一是粘液，它是由粘蛋白糖蛋白形成的高粘性物质。粘蛋白具有多种功能，但重要的是，它们有助于从上皮屏障清除病原体和碎片，并作为先天免疫因子。在这项研究中，我们描述了宿主单糖的需求，可能来自宿主粘蛋白，以实现铜绿假单胞菌在肠道定殖并最终导致秀丽隐杆线虫死亡的能力。我们还证明单糖改变细菌结合秀丽隐杆线虫的能力线虫肠细胞和人肺泡上皮细胞，表明在一系列生物体中存在宿主-病原体相互作用的保守机制。通过更好地了解病原体-粘蛋白相互作用，我们可以开发更好的方法来防止病原体感染。