Vander Elst Niels, Breyne Koen, Steenbrugge Jonas, Gibson Amanda Jane, Smith David George Emslie, Germon Pierre, Werling Dirk, Meyer Evelyne
Laboratory of Biochemistry, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Molecular Neurogenetics Unit, Department of Neurology and Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Front Vet Sci. 2020 Nov 9;7:576583. doi: 10.3389/fvets.2020.576583. eCollection 2020.
Iron is an essential nutrient for bacterial growth. Therefore, bacteria have evolved chelation mechanisms to acquire iron for their survival. Enterobactin, a chelator with high affinity for ferric iron, is secreted by and contributes to its improved bacterial fitness. In this preliminary study, we evaluated enterobactin deficiency both and in the context of mastitis. Firstly, we showed that expression of lipocalin 2, a protein produced by the host that is able to both bind and deplete enterobactin, is increased upon infection in the cow's mastitic mammary gland. Secondly, we demonstrated that enterobactin deficiency does not alter interleukin (IL)-8 expression in bovine mammary epithelial cells and its associated neutrophil recruitment. However, a significantly increased reactive oxygen species production of these neutrophils was observed. Thirdly, we showed there was no significant difference in bacterial growth between the enterobactin-deficient mutant and its wild-type counterpart. However, when further explored in a murine model for bovine mastitis, the enterobactin-deficient mutant vs. the wild-type strain revealed a significant reduction of the bacterial load and, consequently, a decrease in pro-inflammatory cytokines (IL-1α,-1β,-4,-6, and-8). A reduced neutrophilic influx was also observed immunohistochemically. These findings therefore identify interference of the enterobactin iron-scavenging mechanism as a potential measure to decrease the fitness of in the mastitic mammary gland.
铁是细菌生长所必需的营养物质。因此，细菌已经进化出螯合机制来获取铁以维持生存。肠杆菌素是一种对三价铁具有高亲和力的螯合剂，由[细菌名称]分泌并有助于提高其细菌适应性。在这项初步研究中，我们在奶牛乳腺炎的背景下评估了肠杆菌素缺乏在[具体方面1]和[具体方面2]的情况。首先，我们发现脂联素2（一种由宿主产生的既能结合又能消耗肠杆菌素的蛋白质）在奶牛乳腺炎乳腺受到[细菌名称]感染时表达增加。其次，我们证明肠杆菌素缺乏不会改变牛乳腺上皮细胞中白细胞介素（IL）-8的表达及其相关的中性粒细胞募集。然而，观察到这些中性粒细胞的活性氧产生显著增加。第三，我们表明肠杆菌素缺陷型突变体与其野生型对应物之间的细菌生长没有显著差异。然而，当在牛乳腺炎的小鼠模型中进一步研究时，肠杆菌素缺陷型突变体与野生型菌株相比，细菌载量显著降低，因此促炎细胞因子（IL-1α、-1β、-4、-6和-8）减少。免疫组织化学也观察到中性粒细胞流入减少。因此，这些发现确定了肠杆菌素铁清除机制的干扰是一种降低乳腺炎乳腺中[细菌名称]适应性的潜在措施。
