Deng Xiangbin, Zhang Chaoqin, Chen Junwen, Shi Yiyi, Ma Xiaoyu, Wang Yu, Wang Zhanwen, Yu Zhijian, Zheng Jinxin, Chen Zhong
Department of Infectious Diseases and the Key Lab of Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.
Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
J Antibiot (Tokyo). 2021 Dec;74(12):874-883. doi: 10.1038/s41429-021-00475-6. Epub 2021 Sep 6.
This study aims to investigate the antibacterial and anti-biofilm activities of YycG inhibitors H2-60 and H2-81 against Streptococcus agalactiae. A total of 118 nonduplicate S. agalactiae clinical isolates were collected, and the minimal inhibitory concentrations (MICs) of H2-60 and H2-81 were determined. H2-60 and H2-81 inhibit biofilm formation of S. agalactiae were detected by crystal violet staining, and against established biofilms of S. agalactiae were observed by confocal laser scanning microscope. Inhibitory effect of H2-60 and H2-81 on the phosphorylation activity of the HisKA domain of YycG' protein was measured. The MIC/MIC was 3.13/6.25 μM for H2-60 and 6.25/12.5 μM for H2-81 against S. agalactiae, respectively. S. agalactiae planktonic cells can be decreased by H2-60 or H2-81 for more than 3 × log10 CFU ml after 24 h treatment. Biofilm formation of 8 S. agalactiae strains (strong biofilm producers) was significantly reduced after treated with 1/4 × MIC of H2-60 or H2-81 for 24 h. H2-60 and H2-81 could reduce 45.79% and 29.56% of the adherent cells in the established biofilm of S. agalactiae after 72 h treatment, respectively. H2-60 combined with daptomycin reduced 83.63% of the adherent cells in the established biofilm of S. agalactiae, which was significantly better than that of H2-60 (45.79%) or daptomycin (55.07%) alone. The half maximal inhibitory concentrations (IC) were 35.6 μM for H2-60 and 46.3 μM for H2-81 against the HisKA domain of YycG' protein. In conclusion, YycG inhibitors H2-60 and H2-81 exhibit excellent antibacterial and anti-biofilm activities against S. agalactiae.
本研究旨在探究YycG抑制剂H2 - 60和H2 - 81对无乳链球菌的抗菌及抗生物膜活性。共收集了118株非重复的无乳链球菌临床分离株，并测定了H2 - 60和H2 - 81的最低抑菌浓度（MIC）。通过结晶紫染色检测H2 - 60和H2 - 81对无乳链球菌生物膜形成的抑制作用，并用共聚焦激光扫描显微镜观察其对已形成的无乳链球菌生物膜的作用。测定了H2 - 60和H2 - 81对YycG'蛋白HisKA结构域磷酸化活性的抑制作用。H2 - 60和H2 - 81对无乳链球菌的MIC/MIC分别为3.13/6.25 μM和6.25/12.5 μM。处理24小时后，H2 - 60或H2 - 81可使无乳链球菌浮游细胞减少超过3×log10 CFU/ml。用1/4×MIC的H2 - 60或H2 - 81处理24小时后，8株无乳链球菌菌株（强生物膜形成者）的生物膜形成显著减少。处理72小时后，H2 - 60和H2 - 81分别可使已形成的无乳链球菌生物膜中附着细胞减少45.79%和29.56%。H2 - 60与达托霉素联合使用可使已形成的无乳链球菌生物膜中附着细胞减少83.63%，显著优于单独使用H2 - 60（45.79%）或达托霉素（55.07%）。H2 - 60和H2 - 81对YycG'蛋白HisKA结构域的半数最大抑制浓度（IC）分别为35.6 μM和46.3 μM。总之，YycG抑制剂H2 - 60和H2 - 81对无乳链球菌表现出优异的抗菌及抗生物膜活性。
