Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Department of Animal Production, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
Appl Environ Microbiol. 2020 Nov 24;86(24). doi: 10.1128/AEM.00524-20.
Postweaning diarrhea (PWD) is an economically important, multifactorial disease affecting pigs within the first 2 weeks after weaning. The most common agent associated with PWD is enterotoxigenic (ETEC). Currently, antibiotics are used to control PWD, and this has most likely contributed to an increased prevalence of antibiotic-resistant strains. This puts pressure on veterinarians and farmers to decrease or even abandon the use of antibiotics, but these measures need to be supported by alternative strategies for controlling these infections. Naturally derived molecules, such as lactoferrin, could be potential candidates due to their antibacterial or immune-modulating activities. Here, we analyzed the ability of bovine lactoferrin (bLF), porcine lactoferrin (pLF), and ovotransferrin (ovoTF) to inhibit ETEC growth, degrade ETEC virulence factors, and inhibit adherence of these pathogens to porcine intestinal epithelial cells. Our results revealed that bLF and pLF, but not ovoTF, inhibit the growth of ETEC. Furthermore, bLF and pLF can degrade several virulence factors produced by ETEC strains, more specifically F4 fimbriae, F18 fimbriae, and flagellin. On the other hand, ovoTF degrades F18 fimbriae and flagellin but not F4 fimbriae. An adhesion assay showed that bLF, ovoTF, and pLF can decrease the number of bacteria adherent to epithelial cells. Our findings demonstrate that lactoferrin can directly affect porcine ETEC strains, which could allow lactoferrin to serve as an alternative to antimicrobials for the prevention of ETEC infections in piglets. Currently, postweaning F4 and F18 infections in piglets are controlled by the use of antibiotics and zinc oxide, but the use of these antimicrobial agents most likely contributes to an increase in antibiotic resistance. Our work demonstrates that bovine and porcine lactoferrin can inhibit the growth of porcine enterotoxigenic strains. In addition, we also show that lactoferrin can reduce the adherence of these strains to small intestinal epithelial cells, even at a concentration that does not inhibit bacterial growth. This research could allow us to develop lactoferrin as an alternative strategy to prevent enterotoxigenic (ETEC) infections in piglets.
断奶后腹泻（PWD）是一种经济上重要的多因素疾病，影响断奶后 2 周内的猪。与 PWD 最常相关的病原体是肠毒素性（ETEC）。目前，抗生素用于控制 PWD，这很可能导致抗生素耐药菌株的流行增加。这给兽医和农民带来了减少甚至放弃使用抗生素的压力，但这些措施需要得到控制这些感染的替代策略的支持。乳铁蛋白等天然衍生分子由于其抗菌或免疫调节活性，可能成为潜在的候选物。在这里，我们分析了牛乳铁蛋白（bLF）、猪乳铁蛋白（pLF）和卵转铁蛋白（ovoTF）抑制 ETEC 生长、降解 ETEC 毒力因子以及抑制这些病原体与猪肠上皮细胞黏附的能力。我们的结果表明，bLF 和 pLF 但不是 ovoTF 抑制 ETEC 的生长。此外，bLF 和 pLF 可以降解 ETEC 菌株产生的几种毒力因子，更具体地说 F4 菌毛、F18 菌毛和鞭毛。另一方面，ovoTF 降解 F18 菌毛和鞭毛但不降解 F4 菌毛。黏附试验表明，bLF、ovoTF 和 pLF 均可减少黏附于上皮细胞的细菌数量。我们的研究结果表明，乳铁蛋白可以直接影响猪 ETEC 菌株，这使得乳铁蛋白可以作为预防仔猪 ETEC 感染的替代抗生素。目前，仔猪断奶后 F4 和 F18 感染通过使用抗生素和氧化锌来控制，但这些抗菌剂的使用很可能导致抗生素耐药性增加。我们的工作表明，牛和猪乳铁蛋白可以抑制猪肠毒素性菌株的生长。此外，我们还表明，乳铁蛋白即使在不抑制细菌生长的浓度下，也可以减少这些菌株对小肠上皮细胞的黏附。这项研究可以使我们开发乳铁蛋白作为预防仔猪肠毒素性（ETEC）感染的替代策略。
