Sampaio Pedro S, Calado Cecília R C
DREAMS-Interdisciplinary Center for Development and Research in Environment, Applied Management and Space, Faculty of Engineering, Lusophone University of Humanities and Technologies, Campo Grande, 376, 1749‑024 Lisbon, Portugal.
CIMOSM-Centro de Investigação em Modelação e Optimização de Sistemas Multifuncionais, ISEL-Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, R. Conselheiro Emídio Navarro 1, 1959-007 Lisboa, Portugal.
Antibiotics (Basel). 2020 Dec 12;9(12):897. doi: 10.3390/antibiotics9120897.
colonizes the human stomach of half of the world's population. The infection if not treated, persists through life, leading to chronic gastric inflammation, that may progress to severe diseases as peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The first line of treatment, based on 7 to 21 days of two antibiotics associated with a proton pump inhibitor, is, however, already failing most due to patient non-compliance that leads to antibiotic resistance. It is, therefore, urgent to screen for new and more efficient antimicrobials against this bacterium. In this work, Fourier Transform Infrared (FTIR) spectroscopy was evaluated to screen new drugs against in rapid (between 1 to 6 h), and high-throughput mode and based on a microliter volume processes in relation to the agar dilution method. The reference strains 26,695 and J99, were evaluated against a peptide-based antimicrobial and the clinical antibiotic clarithromycin, respectively. After optimization of the assay conditions, as the composition of the incubation mixture, the time of incubation, and spectral pre-processing, it was possible to reproducibly observe the effect of the drug on the bacterial molecular fingerprint as pointed by the spectra principal component analysis. The spectra, obtained from both reference strains, after its incubation with drugs concentrations lower than the MIC, presented peak ratios statistically different ( < 0.05) in relation to the bacteria incubated with drugs concentrations equal or higher to the MIC. It was possible to develop a partial least square regression model, enabling to predict from spectra of both bacteria strains, the drug concentration on the assay, with a high correlation coefficient between predicted and experimental data (0.91) and root square error of 40% of the minimum inhibitory concentration. All this points to the high potential of the technique for drug screening against this fastidious growth bacterium.
它定植于世界上半数人口的胃部。这种感染若不治疗,会终身持续,导致慢性胃炎症,可能会发展成诸如消化性溃疡、胃腺癌和黏膜相关淋巴组织淋巴瘤等严重疾病。然而,基于两种抗生素与质子泵抑制剂联用7至21天的一线治疗方法,由于患者不依从导致抗生素耐药,多数情况下已经失效。因此,迫切需要筛选针对这种细菌的新型且更有效的抗菌药物。在这项研究中,对傅里叶变换红外(FTIR)光谱法进行了评估,以快速(1至6小时之间)、高通量模式且基于微升体积流程,相对于琼脂稀释法来筛选针对该细菌的新药。分别针对基于肽的抗菌剂和临床抗生素克拉霉素,对参考菌株26695和J99进行了评估。在优化了检测条件,如孵育混合物的组成、孵育时间和光谱预处理后,通过光谱主成分分析可以重现性地观察到药物对细菌分子指纹的影响。从两种参考菌株在低于最低抑菌浓度(MIC)的药物浓度下孵育后获得的光谱,与在等于或高于MIC的药物浓度下孵育的细菌相比,呈现出统计学上不同的峰比率(P<0.05)。有可能建立一个偏最小二乘回归模型,能够根据两种细菌菌株的光谱预测检测中的药物浓度,预测数据与实验数据之间具有较高的相关系数(0.91),且均方根误差为最低抑菌浓度的40%。所有这些都表明该技术在针对这种生长苛求细菌进行药物筛选方面具有很高的潜力。