Mil-Homens Dalila, Martins Maria, Barbosa José, Serafim Gabriel, Sarmento Maria J, Pires Rita F, Rodrigues Vitória, Bonifácio Vasco D B, Pinto Sandra N
iBB-Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejskova 3, 18223 Prague 8, Czech Republic.
Antibiotics (Basel). 2021 Jan 8;10(1):56. doi: 10.3390/antibiotics10010056.
, one of the most common pathogens found in hospital-acquired infections, is often resistant to multiple antibiotics. In fact, multidrug-resistant (MDR) producing KPC or OXA-48-like carbapenemases are recognized as a serious global health threat. In this sense, we evaluated the virulence of KPC(+) or OXA-48(+) aiming at potential antimicrobial therapeutics. carbapenemase (KPC) and the expanded-spectrum oxacillinase OXA-48 isolates were obtained from patients treated in medical care units in Lisbon, Portugal. The virulence potential of the clinical isolates was tested using the model. For that, larvae were inoculated using patients KPC(+) and OXA-48(+) isolates. Using this in vivo model, the KPC(+) isolates showed to be, on average, more virulent than OXA-48(+). Virulence was found attenuated when a low bacterial inoculum (one magnitude lower) was tested. In addition, we also report the use of a synthetic polycationic oligomer (L-OEI-h) as a potential antimicrobial agent to fight infectious diseases caused by MDR bacteria. L-OEI-h has a broad-spectrum antibacterial activity and exerts a significantly bactericidal activity within the first 5-30 min treatment, causing lysis of the cytoplasmic membrane. Importantly, the polycationic oligomer showed low toxicity against in vitro models and no visible cytotoxicity (measured by survival and health index) was noted on the in vivo model , thus L-OEI-h is foreseen as a promising polymer therapeutic for the treatment of MDR infections.
作为医院获得性感染中最常见的病原体之一，通常对多种抗生素具有耐药性。事实上，产生KPC或OXA - 48样碳青霉烯酶的多重耐药（MDR）菌株被认为是对全球健康的严重威胁。从这个意义上讲，我们针对潜在的抗菌治疗方法评估了产KPC或OXA - 48碳青霉烯酶（KPC）和超广谱β - 内酰胺酶OXA - 48分离株的毒力。这些碳青霉烯酶（KPC）和超广谱β - 内酰胺酶OXA - 48分离株取自葡萄牙里斯本医疗单位接受治疗的患者。使用该模型测试了临床分离株的毒力潜力。为此，用患者的KPC（+）和OXA - 48（+）分离株接种幼虫。使用这种体内模型，KPC（+）分离株平均显示出比OXA - 48（+）更强的毒力。当测试低细菌接种量（低一个数量级）时，发现毒力减弱。此外，我们还报告了使用一种合成聚阳离子低聚物（L - OEI - h）作为对抗由MDR细菌引起的传染病的潜在抗菌剂。L - OEI - h具有广谱抗菌活性，并在最初的5 - 30分钟治疗内发挥显著的杀菌活性，导致细胞质膜裂解。重要的是，该聚阳离子低聚物对体外模型显示出低毒性，并且在体内模型上未观察到明显的细胞毒性（通过存活率和健康指数测量），因此L - OEI - h被视为治疗MDR感染的一种有前景的聚合物疗法。
