Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States.
Department of Chemistry, Vanderbilt University, Nashville, TN, United States.
Front Cell Infect Microbiol. 2021 Sep 20;11:740872. doi: 10.3389/fcimb.2021.740872. eCollection 2021.
Group B (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.
B 组链球菌（GBS）是导致母婴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。感染还可能导致母婴败血症，这可能导致死亡率上升。目前，GBS 感染的治疗方法包括在妊娠晚期对 GBS 定植呈阳性的母亲给予一次产时抗生素预防。乳铁蛋白是一种在人乳、黏膜上皮和中性粒细胞次级颗粒中表达的抗菌肽。我们之前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隔离铁的能力。我们通过评估纯化的人乳乳铁蛋白对一组表型和遗传上多样化的 GBS 分离株的影响，扩展了该研究。在所筛选的 25 株 GBS 分离株中，乳铁蛋白减少了 14 株细菌生长，减少了 21 株生物膜形成。对数据进行分层分析，我们观察到在 250-750μg/ml 乳铁蛋白浓度下，定植菌株比侵袭性分离株更易受到乳铁蛋白生长抑制活性的影响。用 750μg/ml 的乳铁蛋白处理导致不同离散序列型之间的细菌生长和生物膜形成存在差异。在荚膜血清型 1a 和 III 之间也观察到了细菌生长的差异。与新生儿败血症分离株相比，母体分离株在细菌生长方面对乳铁蛋白更敏感，但在生物膜形成方面则不敏感。最后，高生物膜形成的 GBS 菌株在所有测试的分离株中受乳铁蛋白的影响更大。总之，这项研究表明，乳铁蛋白对广泛的 GBS 分离株具有抗菌和抗生物膜特性，母体分离的定植菌株最敏感。
