Necel Agnieszka, Bloch Sylwia, Topka-Bielecka Gracja, Janiszewska Agata, Łukasiak Aleksandra, Nejman-Faleńczyk Bożena, Węgrzyn Grzegorz
Department of Molecular Biology, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
Antibiotics (Basel). 2022 May 25;11(6):712. doi: 10.3390/antibiotics11060712.
Apart from antibiotic resistance of pathogenic bacteria, the formation of biofilms is a feature that makes bacterial infections especially difficulty to treat. Shiga toxin-producing (STEC) strains are dangerous pathogens, causing severe infections in humans, and capable of biofilm production. We have reported previously the identification and characterization of the vB_Eco4-M7 bacteriophage, infecting various STEC strains. It was suggested that this phage might be potentially used in phage therapy against these bacteria. Here, we tested the effects of vB_Eco4-M7 alone or in a phage cocktail with another STEC-infecting phage, and/or in a combination with different antibiotics (ciprofloxacin and rifampicin) on biofilm formed by a model STEC strain, named O157:H7 (ST2-8624). The vB_Eco4-M7 phage appeared effective in anti-biofilm action in all these experimental conditions (2-3-fold reduction of the biofilm density, and 2-3 orders of magnitude reduction of the number of bacterial cells). However, the highest efficiency in reducing a biofilm's density and number of bacterial cells was observed when phage infection preceded antibiotic treatment (6-fold reduction of the biofilm density, and 5-6 orders of magnitude reduction of the number of bacterial cells). Previous reports indicated that the use of antibiotics to treat STEC-caused infections might be dangerous due to the induction of Shiga toxin-converting prophages from bacterial genomes under stress conditions caused by antibacterial agents. We found that ciprofloxacin was almost as efficient in inducing prophages from the O15:H7 (ST2-8624) genome as a classical inducer, mitomycin C, while no detectable prophage induction could be observed in rifampicin-treated STEC cells. Therefore, we conclude the latter antibiotic or similarly acting compounds might be candidate(s) as effective and safe drug(s) when used in combination with phage therapy to combat STEC-mediated infections.
除了病原菌的抗生素耐药性外，生物膜的形成是使细菌感染特别难以治疗的一个特征。产志贺毒素（STEC）菌株是危险的病原体，可导致人类严重感染，并且能够产生生物膜。我们之前报道了感染各种STEC菌株的vB_Eco4-M7噬菌体的鉴定和特性。有人提出这种噬菌体可能潜在地用于针对这些细菌的噬菌体疗法。在这里，我们测试了单独的vB_Eco4-M7或与另一种感染STEC的噬菌体组成的噬菌体鸡尾酒，和/或与不同抗生素（环丙沙星和利福平）联合使用对一种名为O157:H7（ST2-8624）的模型STEC菌株形成的生物膜的影响。vB_Eco4-M7噬菌体在所有这些实验条件下都表现出有效的抗生物膜作用（生物膜密度降低2-3倍，细菌细胞数量减少2-3个数量级）。然而，当噬菌体感染先于抗生素治疗时，观察到生物膜密度和细菌细胞数量降低的效率最高（生物膜密度降低6倍，细菌细胞数量减少5-6个数量级）。先前的报道表明，由于在抗菌剂引起的应激条件下从细菌基因组中诱导出志贺毒素转化前噬菌体，使用抗生素治疗STEC引起的感染可能是危险的。我们发现环丙沙星在从O15:H7（ST2-8624）基因组中诱导前噬菌体方面几乎与经典诱导剂丝裂霉素C一样有效，而在利福平处理的STEC细胞中未观察到可检测到的前噬菌体诱导。因此，我们得出结论，后一种抗生素或类似作用的化合物在与噬菌体疗法联合使用以对抗STEC介导的感染时可能是有效和安全的药物候选物。
