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乳铁蛋白和乳铁蛋白肽 B 可减少肠道共生菌脆弱拟杆菌和普通拟杆菌的黏附和生物膜形成。

Lactoferrin and lactoferricin B reduce adhesion and biofilm formation in the intestinal symbionts Bacteroides fragilis and Bacteroides thetaiotaomicron.

机构信息

Medical Microbiology Department, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, Brazil; Department of Pharmaceutical Technology, Faculty of Pharmacy, Fluminense Federal University, Brazil.

Medical Microbiology Department, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, Brazil.

出版信息

Anaerobe. 2020 Aug;64:102232. doi: 10.1016/j.anaerobe.2020.102232. Epub 2020 Jul 4.

DOI:10.1016/j.anaerobe.2020.102232
PMID:32634470
Abstract

Several factors affect the composition of species that inhabit our intestinal tract, including mode of delivery, genetics and nutrition. Antimicrobial peptides and proteins secreted in the gastrointestinal tract are powerful tools against bacteria. Lactoferrin (LF) inhibits the growth of several bacterial species, such as Enterobacteriaceae, but may stimulate probiotic bacteria. Activity of LF against gut symbiotic species of the Bacteroides genus could give us insights on how these species colonize the gut. We investigated the effects of the antimicrobial protein lactoferrin and its derived peptide, lactoferricin B on two species of strict anaerobes, opportunistic pathogens that cause diseases in both adults and children, commonly found in the microbiota of the human gastrointestinal tract, Bacteroides fragilis and B. thetaiotaomicron., In vitro biofilm formation and binding to laminin were strongly inhibited by a low concentration of lactoferrin (12.5 μg/ml). Conversely, the growth of the strains in a micro-dilution assay in minimal media with different iron sources was not affected by physiological concentrations (2 mg/ml) of apo-lactoferrin or holo-lactoferrin. The combination of lactoferrin with antibiotics in synergism assays was also negative. The lactoferricin B fragment was also unable to inhibit growth in a similar test with concentrations of up to 32 μg/ml. Resistance to lactoferrin could confer an advantage to these species, even when high amount of this protein is present in the gastrointestinal tract. However, colonization is hampered by the binding and biofilm inhibitiory effect of lactoferrin, which may explain the low prevalence of Bacteroides in healthy babies. Resistance to this antimicrobial protein may help understand the success of these opportunistic pathogens during infection in the peritoneum.

摘要

有几个因素会影响栖息在我们肠道内的物种组成,包括分娩方式、遗传和营养。在胃肠道中分泌的抗菌肽和蛋白质是对抗细菌的有力工具。乳铁蛋白 (LF) 可以抑制多种细菌的生长,例如肠杆菌科,但也可能刺激益生菌。LF 对肠道共生的拟杆菌属物种的活性可以让我们深入了解这些物种是如何定植肠道的。我们研究了抗菌蛋白乳铁蛋白及其衍生肽乳铁蛋白素 B 对两种严格厌氧菌的影响,这两种菌都是机会致病菌,在成人和儿童中都会引起疾病,通常存在于人类胃肠道微生物群中,脆弱拟杆菌和双歧杆菌。低浓度乳铁蛋白(12.5μg/ml)强烈抑制两种菌株的体外生物膜形成和与层粘连蛋白的结合。相反,在含有不同铁源的最小培养基中的微量稀释测定中,生理浓度(2mg/ml)的脱铁乳铁蛋白或全铁乳铁蛋白对菌株的生长没有影响。协同测定中乳铁蛋白与抗生素的组合也呈阴性。乳铁蛋白素 B 片段在类似的测试中浓度高达 32μg/ml 也无法抑制生长。对乳铁蛋白的耐药性可能使这些物种具有优势,即使在胃肠道中存在大量这种蛋白质的情况下也是如此。然而,乳铁蛋白的结合和生物膜抑制作用阻碍了定植,这可能解释了健康婴儿中拟杆菌属低流行的原因。对这种抗菌蛋白的耐药性可能有助于理解这些机会致病菌在腹膜感染期间的成功。

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