SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection.
SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection.
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DOI：
10.3389/fmicb.2021.625952
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发表时间：
2021
影响因子：
5.2
通讯作者：
Nibbering PH
中科院分区：
文献类型：
--
作者：
Scheper H;Wubbolts JM;Verhagen JAM;de Visser AW;van der Wal RJP;Visser LG;de Boer MGJ;Nibbering PH
人工关节感染（PJI）是关节置换术的严重并发症。由于生物膜和持久性的形成，目前的治疗策略往往失败。因此，迫切需要创新的抗生物膜和抗粘剂。具有广泛抗菌活性的抗菌肽可能是这样的候选者。建立了一种体外模拟PJI的模型，该模型包括利福平/环丙沙星暴露，成熟的耐甲氧西林金黄色葡萄球菌（MRSA）生物膜在聚苯乙烯板，钛/铝/铌盘和假体关节衬垫上。从这些生物膜中获得和居住在这些生物膜中的细菌暴露于SAAP-148、酰基depsipeptide-4、LL-37和pexiganan。微量热法用于监测这些模型中细菌的热流。将成熟的生物膜每天暴露于利福平/环丙沙星3天，MRSA减少了4倍。长时间的抗生素暴露并没有进一步减少细菌数量。微量热量测定证实了这些顽固分子的低代谢活性。SAAP-148和pexiganan消除了持续基因，但LL-37没有，而ADEP4减少了持续基因的数量。SAAP-148进一步根除各种表面上暴露于抗生素的成熟生物膜中的顽固分子。综上所述，各种表面上暴露于抗生素的成熟MRSA生物膜已被开发为PJI的体外模型。SAAP-148对从生物膜和这些模型中获得的顽固分子非常有效。抗生素暴露，相关表面上成熟的生物膜可以帮助寻找新的治疗策略来对抗生物膜相关感染。
Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.
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作者：
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发表时间：
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作者：
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