Cornejo Santiago, Barber Cassandra, Thoresen Merrilee, Lawrence Mark, Seo Keun Seok, Woolums Amelia
Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
Front Vet Sci. 2024 Aug 12;11:1430919. doi: 10.3389/fvets.2024.1430919. eCollection 2024.
Mass treatment with antibiotics at arrival has been the mainstay for bovine respiratory disease (BRD) control but there is an increase in antimicrobial-resistant bacteria being shed from treated cattle. BRD is a disease complex that results from the interaction of viruses or bacteria and susceptible animals with inappropriate immunity. With bacteria being the only feasibly treatable agent and the emergence of antimicrobial resistance, decreased efficacy of commonly used antibiotics could threaten livestock health. There is a need for new antimicrobial alternatives that could be used to control disease. Naturally occurring antimicrobial peptides (AMP) have been proposed to address this need. Here we tested the effect of bovine myeloid antimicrobial peptide-28 (BMAP-28), a synthetic BMAP-28 analog Syn-1, and bactenecin 5 (Bac-5) on (Mh) using a quantitative culture method and the broth microdilution method to determine minimum inhibitory and bactericidal concentrations (MIC and MBC). We also tested the antiviral effect of these AMP against bovine herpes-1 (BHV-1) and bovine respiratory syncytial virus (BRSV) using the Reed and Muench method to calculate the viral titers after treatment. We demonstrated that BMAP-28 and Syn-1 can inhibit Mh growth and BMAP-28 can inhibit replication of BHV-1 and BRSV. Moreover, we showed that BMAP-28 and Bac-5 can be used together to inhibit Mh growth. When used alone, the MIC of BMAP-28 and Bac-5 was 64 and 128 μg/mL respectively, but when applied together, their MIC ranged from 0.25-16 for BMAP-28 and 8-64 μg/mL for Bac-5, resulting in a decrease in concentration of up to 256 and 16-fold, respectively. The synergistic interaction between those peptides resulted in concentrations that could be well tolerated by cells. Our results demonstrate that bovine cathelicidins could be used as alternatives to antimicrobials against BRD pathogens. These findings introduce a path to discovering new antimicrobials and determining how these peptides could be tailored to improve cattle health.
到达时使用抗生素进行大规模治疗一直是控制牛呼吸道疾病(BRD)的主要手段,但接受治疗的牛排出的抗菌耐药菌数量有所增加。BRD是一种疾病复合体,由病毒或细菌与免疫力不佳的易感动物相互作用引起。由于细菌是唯一可实际治疗的病原体,且抗菌耐药性不断出现,常用抗生素疗效降低可能会威胁家畜健康。因此需要可用于控制疾病的新型抗菌替代品。天然存在的抗菌肽(AMP)被认为可以满足这一需求。在此,我们使用定量培养法和肉汤微量稀释法来测定最低抑菌浓度和最低杀菌浓度(MIC和MBC),测试了牛髓样抗菌肽-28(BMAP-28)、一种合成的BMAP-28类似物Syn-1以及杆菌肽5(Bac-5)对溶血曼氏杆菌(Mh)的作用。我们还使用里德-孟奇方法计算处理后的病毒滴度,测试了这些抗菌肽对牛疱疹病毒1型(BHV-1)和牛呼吸道合胞病毒(BRSV)的抗病毒效果。我们证明了BMAP-28和Syn-1可以抑制Mh生长,并且BMAP-28可以抑制BHV-1和BRSV的复制。此外,我们还表明BMAP-28和Bac-5可以联合使用来抑制Mh生长。单独使用时,BMAP-28和Bac-5的MIC分别为64和128μg/mL,但联合使用时,BMAP-28的MIC范围为0.25 - 16μg/mL,Bac-5的MIC范围为8 - 64μg/mL,浓度分别降低了256倍和16倍。这些肽之间的协同相互作用产生的浓度细胞能够很好地耐受。我们的结果表明,牛cathelicidin可作为抗BRD病原体抗菌剂的替代品。这些发现为发现新型抗菌剂以及确定如何定制这些肽以改善牛的健康状况开辟了一条道路。