Faleiro Leonor, Marques Ana, Martins João, Jordão Luísa, Nogueira Isabel, Gumerova Nadiia I, Rompel Annette, Aureliano Manuel
Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
Algarve Biomedical Center-Research Institute, 8005-139 Faro, Portugal.
Biology (Basel). 2022 Jun 30;11(7):994. doi: 10.3390/biology11070994.
The increase in bacterial resistance to antibiotics has led researchers to find new compounds or find combinations between different compounds with potential antibacterial action and with the ability to prevent the development of antibiotic resistance. Polyoxotungstates (POTs) are inorganic clusters that may fulfill that need, either individually or in combination with antibiotics. Herein, we report the ability of the polyoxotungstates (POTs) with Wells-Dawson P2W18, P2W17, P2W15, and Preyssler P5W30 type structures to differently affect Gram-negative and Gram-positive microorganisms, either susceptible or resistant to antibiotics. The compound P5W30 showed the highest activity against the majority of the tested bacterial strains in comparison with the other tested POTs (P2W15, P2W17 and P2W18) that did not show inhibition zones for the Gram-negative bacteria, A. baumanii I73775, E. coli DSM 1077, E. coli I73194, K. pneumoniae I7092374, and P. aeruginosa C46281). Generally, the results evidenced that Gram-positive bacteria are more susceptible to the POTs tested. The compound P5W30 was the one most active against S. aureus ATCC 6538 and MRSA16, reaching <0.83 mg·mL−1 (100 μM) and 4.96 mg·mL−1 (600 μM), respectively. Moreover, it was verified by NMR spectroscopy that the most promising POT, P5W30, remains intact under all the experimental conditions, after 24 h at 37 °C. This prompted us to further evaluate the anti-quorum sensing activity of P5W30 using the biosensor Chromobacterium violaceum CV026, as well as its antibiofilm activity both individually and in combination with the antibiotic cefoxitin against the methicillin-resistant Staphylococcus aureus 16 (MRSA16). P5W30 showed a synergistic antibacterial effect with the antibiotic cefoxitin and chloramphenicol against MRSA16. Moreover, the antibiofilm activity of P5W30 was more pronounced when used individually, in comparison with the combination with the antibiotic cefoxitin. Finally, the antiviral activity of P5W30 was tested using the coliphage Qβ, showing a dose-dependent response. The maximum inactivation was observed at 750 μM (6.23 mg·mL−1). In sum, P5W30 shows anti-quorum sensing and antibiofilm activities besides being a potent antibacterial agent against S. aureus and to exhibit antiviral activities against enteric viruses.
细菌对抗生素耐药性的增加促使研究人员寻找新的化合物，或寻找具有潜在抗菌作用且能够防止抗生素耐药性产生的不同化合物之间的组合。多金属氧酸盐（POTs）是无机簇合物，它们可能单独或与抗生素联合满足这一需求。在此，我们报告了具有Wells-Dawson型P2W18、P2W17、P2W15结构以及Preyssler型P5W30结构的多金属氧酸盐（POTs）对革兰氏阴性和革兰氏阳性微生物（无论对抗生素敏感与否）产生不同影响的能力。与其他测试的POTs（P2W15、P2W17和P2W18）相比，化合物P5W30对大多数测试细菌菌株表现出最高活性，其他测试的POTs对革兰氏阴性菌鲍曼不动杆菌I73775、大肠杆菌DSM 1077、大肠杆菌I73194、肺炎克雷伯菌I7092374和铜绿假单胞菌C46281未显示抑菌圈。总体而言，结果表明革兰氏阳性菌对所测试的POTs更敏感。化合物P5W30对金黄色葡萄球菌ATCC 6538和耐甲氧西林金黄色葡萄球菌16（MRSA16）的活性最高，其最低抑菌浓度分别达到<0.83 mg·mL−1（100 μM）和4.96 mg·mL−1（600 μM）。此外，通过核磁共振光谱证实，最有前景的POT，即P5W30，在37℃下24小时后的所有实验条件下均保持完整。这促使我们进一步评估P5W30使用紫色杆菌素生物传感器CV026的群体感应抑制活性，以及其单独和与抗生素头孢西丁联合对耐甲氧西林金黄色葡萄球菌16（MRSA16）的抗生物膜活性。P5W30与抗生素头孢西丁和氯霉素对MRSA16显示出协同抗菌作用。此外，与与抗生素头孢西丁联合使用相比，P5W30单独使用时的抗生物膜活性更显著。最后，使用大肠杆菌噬菌体Qβ测试了P5W30的抗病毒活性，显示出剂量依赖性反应。在750 μM（6.23 mg·mL−1）时观察到最大失活。总之，P5W30除了是一种针对金黄色葡萄球菌的强效抗菌剂并对肠道病毒具有抗病毒活性外，还表现出群体感应抑制和抗生物膜活性。
