Raeder Synnøve Brandt, Sandbakken Erik Thorvaldsen, Nepal Anala, Løseth Kirsti, Bergh Kåre, Witsø Eivind, Otterlei Marit
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Department of Orthopaedic Surgery, St. Olav University Hospital, Trondheim, Norway.
Front Microbiol. 2021 Mar 17;12:631557. doi: 10.3389/fmicb.2021.631557. eCollection 2021.
Antimicrobial resistance is an increasing threat to global health and challenges the way we treat infections. Peptides containing the PCNA interacting motif APIM (APIM-peptides) were recently shown to bind to the bacterial PCNA homolog, the beta (β)-clamp, and to have both antibacterial and anti-mutagenic activities. In this study we explore the antibacterial effects of these peptides on , a bacterial species commonly found in prosthetic joint infections (PJI). Drug-resistant bacterial isolates from PJIs often lead to difficult-to-treat chronic infections. We show that APIM-peptides have a rapid bactericidal effect which when used at sublethal levels also increase the efficacy of gentamicin. In addition, APIM-peptides reduce development and eliminate already existing biofilm. To study the potential use of APIM-peptides to prevent PJI, we used an bone graft model in rats where APIM-peptide, gentamicin, or a combination of the two was added to cement. The bone grafts containing cement with the combination was more effective than cement containing only gentamicin, which is the current standard of care. In summary, these results suggest that APIM-peptides can be a promising new drug candidate for anti-infective implant materials to use in the fight against resistant bacteria and chronic PJI.
抗菌耐药性对全球健康构成了日益严重的威胁，并对我们治疗感染的方式提出了挑战。最近发现，含有增殖细胞核抗原（PCNA）相互作用基序APIM的肽（APIM肽）可与细菌PCNA同源物β钳夹结合，并具有抗菌和抗诱变活性。在本研究中，我们探究了这些肽对一种常见于人工关节感染（PJI）中的细菌的抗菌作用。来自PJI的耐药细菌分离株常常导致难以治疗的慢性感染。我们发现，APIM肽具有快速杀菌作用，在亚致死水平使用时还能提高庆大霉素的疗效。此外，APIM肽可减少生物膜的形成并消除已形成的生物膜。为了研究APIM肽预防PJI的潜在用途，我们在大鼠的骨移植模型中，将APIM肽、庆大霉素或两者的组合添加到骨水泥中。含有联合用药骨水泥的骨移植比仅含庆大霉素的骨水泥（目前的护理标准）更有效。总之，这些结果表明，APIM肽有望成为一种新型抗感染植入材料的候选药物，用于对抗耐药细菌和慢性PJI。
