Artini Marco, Paris Irene, Imperlini Esther, Buonocore Francesco, Vrenna Gianluca, Papa Rosanna, Selan Laura
Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Viterbo, Italy.
Front Cell Infect Microbiol. 2025 Feb 14;15:1526246. doi: 10.3389/fcimb.2025.1526246. eCollection 2025.
About 71% of healthcare-associated infections are due to antibiotic-resistant bacteria, such as carbapenem-resistant , classified by World Health Organization into a critical priority group of pathogens. The antimicrobial resistance profile of relies on its ability to produce several virulence factors, including biofilm formation. Its ability to adhere and persist on surfaces as biofilm has contributed to its pathogenicity and drug resistance. In this study, the ability of an antimicrobial peptide (a chionodracine-derived peptide named KHS-Cnd) to inhibit or reduce biofilm formation was investigated as an example of a potential strategy to counteract infections caused by biofilm-forming pathogens. To this aim, the antimicrobial profiles were first analyzed in selected strains, two reference and six clinical strains, all biofilm-forming with different capability, regardless of whether they are drug resistant or sensitive. Successively, we investigated the bactericidal activity of the peptide that showed MIC values ranging from 5 to 10 µM and a significative antibiofilm activity on all tested strains at sub-inhibitory concentrations. In fact, KHS-Cnd can hinder biofilm strains formation with an inhibition percentage ranging between 65% and 10%. Also a statistically significant reduction of mature biofilm ranging from 20% to 50% was observed in four out of eight tested strains. KHS-Cnd impacts various stages of biofilm formation, including the inhibition of surface-associated and twitching motilities depending on the different strain. In particular, our results showed that only two strains possessed surface-associated motility that was strongly impaired by KHS-Cnd treatment; three clinical strains, instead, showed twitching motility, whose inhibition for two of them was evident after 24 h of incubation with peptide. Moreover, the invasion of pulmonary cells by was significantly impaired with a reduction of about 32% after treatment with 1.25 µM KHS-Cnd. Finally, when the peptide was used together with ceftazidime/avibactam against resistant strains, it was able to reduce the minimal inhibitory concentration of antibiotics needed to inhibit the microorganism growth.
约71%的医疗保健相关感染是由耐抗生素细菌引起的，如耐碳青霉烯类细菌，世界卫生组织将其列为关键优先病原体组。[细菌名称]的抗菌耐药性特征依赖于其产生多种毒力因子的能力，包括生物膜形成。它以生物膜形式粘附并持续存在于表面的能力促成了其致病性和耐药性。在本研究中，以一种抗菌肽（一种名为KHS-Cnd的源自雪龙德拉辛的肽）抑制或减少生物膜形成的能力为例，探讨应对由形成生物膜的病原体引起的感染的潜在策略。为此，首先在选定的[细菌名称]菌株中分析抗菌谱，包括两株参考菌株和六株临床菌株，所有菌株均具有不同能力的生物膜形成能力，无论它们是耐药还是敏感。随后，我们研究了该肽的杀菌活性，其最低抑菌浓度（MIC）值为5至10μM，并且在亚抑菌浓度下对所有测试菌株均具有显著的抗生物膜活性。事实上，KHS-Cnd可以阻碍[细菌名称]菌株形成生物膜，抑制率在65%至80%之间。在八株测试的[细菌名称]菌株中，有四株还观察到成熟生物膜有统计学意义的减少，减少幅度在20%至50%之间。KHS-Cnd影响生物膜形成的各个阶段，包括根据不同菌株抑制表面相关运动和抽搐运动。特别是，我们的结果表明，只有两株菌株具有表面相关运动，经KHS-Cnd处理后受到强烈损害；相反，三株临床菌株表现出抽搐运动，其中两株在与肽孵育24小时后其抑制作用明显。此外，用1.25μM KHS-Cnd处理后，[细菌名称]对肺细胞的侵袭明显受损，减少了约32%。最后，当该肽与头孢他啶/阿维巴坦联合用于对抗耐药[细菌名称]菌株时，它能够降低抑制微生物生长所需的抗生素最低抑菌浓度。
