Otani Satoshi, Hiramatsu Kazufumi, Hashinaga Kazuhiko, Komiya Kosaku, Umeki Kenji, Kishi Kenji, Kadota Jun-Ichi
Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan.
Department of Medical Safety Management, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan.
J Infect Chemother. 2018 Jun;24(6):428-433. doi: 10.1016/j.jiac.2018.01.007. Epub 2018 Feb 12.
Pseudomonas aeruginosa exhibits the biofilm mode of growth and causes chronic as well as acute infections in humans. Several reports have shown that the treatments with sub-minimum inhibitory concentrations (sub-MICs) of antimicrobial agents influence biofilm formation by P. aeruginosa. The antibiotic ceftazidime (CAZ) is used to treat P. aeruginosa infections, but few studies have examined the effects of β-lactams on biofilm formation by P. aeruginosa. In this study, we investigated the role of sub-MICs of CAZ in the formation of P. aeruginosa biofilms. 1/4 × MIC CAZ reduced the biofilm volume of P. aeruginosa PAO1, as quantified by crystal violet staining. The formation of P. aeruginosa PAO1 biofilms treated with 1/4 × MIC CAZ were observed by confocal laser scanning microscopy. They were more heterogeneous than the PAO1 biofilms without CAZ treatment. Furthermore, sub-MICs of CAZ inhibited the twitching motility, which played an important role in mature biofilm formation. 1/4 × MIC CAZ also reduced the gene expressions of lecA, lecB, pel and psl, which mediate the adhesion and polysaccharide matrix synthesis of P. aeruginosa. These effects suggest that sub-MICs of CAZ may affect a number of stages of biofilm formation. Investigating the effects of sub-MIC antibiotics on targeted bacterial biofilm may lead to the development of future antibiotic treatment modalities.
铜绿假单胞菌呈现生物膜生长模式，可导致人类慢性和急性感染。多项报告表明，用低于最低抑菌浓度（亚 MIC）的抗菌剂处理会影响铜绿假单胞菌的生物膜形成。抗生素头孢他啶（CAZ）用于治疗铜绿假单胞菌感染，但很少有研究考察β-内酰胺类药物对铜绿假单胞菌生物膜形成的影响。在本研究中，我们调查了 CAZ 的亚 MIC 在铜绿假单胞菌生物膜形成中的作用。通过结晶紫染色定量分析，1/4×MIC 的 CAZ 降低了铜绿假单胞菌 PAO1 的生物膜体积。用共聚焦激光扫描显微镜观察了经 1/4×MIC CAZ 处理的铜绿假单胞菌 PAO1 生物膜的形成。它们比未用 CAZ 处理的 PAO1 生物膜更具异质性。此外，CAZ 的亚 MIC 抑制了在成熟生物膜形成中起重要作用的颤动运动。1/4×MIC 的 CAZ 还降低了介导铜绿假单胞菌黏附及多糖基质合成的 lecA、lecB、pel 和 psl 的基因表达。这些效应表明，CAZ 的亚 MIC 可能影响生物膜形成的多个阶段。研究亚 MIC 抗生素对靶向细菌生物膜的影响可能会带来未来抗生素治疗方式的发展。
