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Analysis of Susceptibility to the Antimicrobial and Anti-Biofilm Activity of Human Milk Lactoferrin in Clinical Strains of Streptococcus agalactiae With Diverse Capsular and Sequence Types
Frontiers in Cellular and Infection Microbiology ( IF 5.7 ) Pub Date : 2021-09-20 , DOI: 10.3389/fcimb.2021.740872
Jacky Lu 1 , Miriam A Guevara 1 , Jamisha D Francis 1 , Sabrina K Spicer 2 , Rebecca E Moore 2 , Schuyler A Chambers 2 , Kelly M Craft 3 , Shannon D Manning 4 , Steven D Townsend 2 , Jennifer A Gaddy 1, 5, 6
Affiliation  

Group B Streptococcus (GBS) is one of the leading infection-related causes of adverse maternal and neonatal outcomes. This includes chorioamnionitis, which leads to preterm ruptures of membranes and can ultimately result in preterm or stillbirth. Infection can also lead to maternal and neonatal sepsis that may contribute to mortality. Currently, treatment for GBS infection include a bolus of intrapartum antibiotic prophylaxis to mothers testing positive for GBS colonization during late pregnancy. Lactoferrin is an antimicrobial peptide expressed in human breast milk, mucosal epithelia, and secondary granules of neutrophils. We previously demonstrated that lactoferrin possesses antimicrobial and antibiofilm properties against several strains of GBS. This is largely due to the ability of lactoferrin to bind and sequester iron. We expanded upon that study by assessing the effects of purified human breast milk lactoferrin against a panel of phenotypically and genetically diverse isolates of GBS. Of the 25 GBS isolates screened, lactoferrin reduced bacterial growth in 14 and biofilm formation in 21 strains. Stratifying the data, we observed that colonizing strains were more susceptible to the growth inhibition activity of lactoferrin than invasive isolates at lactoferrin concentrations between 250-750 µg/mL. Treatment with 750 µg/mL of lactoferrin resulted in differences in bacterial growth and biofilm formation between discrete sequence types. Differences in bacterial growth were also observed between capsular serotypes 1a and III. Maternally isolated strains were more susceptible to lactoferrin with respect to bacterial growth, but not biofilm formation, compared to neonatal sepsis isolates. Finally, high biofilm forming GBS strains were more impacted by lactoferrin across all isolates tested. Taken together, this study demonstrates that lactoferrin possesses antimicrobial and antibiofilm properties against a wide range of GBS isolates, with maternally isolated colonizing strains being the most susceptible.



中文翻译:

不同荚膜和序列类型的无乳链球菌临床菌株对人乳乳铁蛋白抗菌和抗生物膜活性的敏感性分析

B组链球菌(GBS) 是导致孕产妇和新生儿不良结局的主要感染相关原因之一。这包括绒毛膜羊膜炎,它会导致胎膜早破并最终导致早产或死产。感染还可能导致可能导致死亡的孕产妇和新生儿败血症。目前,GBS 感染的治疗包括对妊娠晚期 GBS 定植阳性的母亲进行产时抗生素预防性推注。乳铁蛋白是一种抗菌肽,在人母乳、黏膜上皮细胞和中性粒细胞次级颗粒中表达。我们之前已经证明乳铁蛋白对几种 GBS 菌株具有抗菌和抗生物膜特性。这主要是由于乳铁蛋白结合和螯合铁的能力。我们通过评估纯化的人母乳乳铁蛋白对一组表型和遗传多样性的 GBS 分离物的影响来扩展该研究。在筛选的 25 个 GBS 分离株中,乳铁蛋白减少了 14 个菌株的细菌生长和 21 个菌株的生物膜形成。对数据进行分层,我们观察到,在乳铁蛋白浓度在 250-750 µg/mL 之间时,定植菌株比侵入性分离株更容易受到乳铁蛋白的生长抑制活性的影响。用 750 µg/mL 乳铁蛋白处理导致离散序列类型之间细菌生长和生物膜形成的差异。在荚膜血清型 1a 和 III 之间也观察到细菌生长的差异。在细菌生长方面,母体分离的菌株对乳铁蛋白更敏感,但对生物膜形成不敏感,与新生儿脓毒症分离株相比。最后,在所有测试的分离物中,高生物膜形成 GBS 菌株受乳铁蛋白的影响更大。总之,这项研究表明,乳铁蛋白对多种 GBS 分离株具有抗菌和抗生物膜特性,其中母系分离的定植菌株最敏感。

更新日期:2021-09-20
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