[ODP7C] c. Others

[ODP-218/WS10-3] ATP-dependent Lon protease regulates awakening from ciprofloxacin-induced persistence

Naoki Maekawa¹, Kengo Itadera², Junichi Ishihara², Satsuki Kajiya³, Daiki Tanaka⁴, Tetsushi Sekiguchi⁴, Shuichi Shoji³, Masami Ishibashi¹, Hiroki Takahashi², ○Akiko Takaya^1,2 (¹Dep. Nat. Prod. Chem., Grad. Sch. Pharm. Sci., Chiba Univ., ²MMRC, Chiba Univ., ³Fac. Sci. Eng., Waseda Univ., ⁴Res. Org. Nano Life Inno., Waseda Univ.)

Quinolones such as ciprofloxacin are broad-spectrum antibiotics, which are used for the treatment of different infectious diseases associated with Enterobacteriaceae. However, the wide use as well as overuse of quinolones against diverse infections has led to the increased emergence of quinolone-resistant bacterial strains. The emergence of resistant bacteria is thought to be related to the antibiotic-induced persistence. Here, we focused on how ATP-dependent Lon protease regulates the ciprofloxacin-induced persistence. After treatment with high dose of ciprofloxacin, 1% of wild-type cells were observed at 24 hours. In contrast, only few colonies of Lon-deficient cells were detected at 3 hours and no colonies were observed at 24 hours. Single-cell imaging, however, showed that the number of remained cells after treatment with ciprofloxacin were not influenced by Lon-depletion. Lon-deficient cells treated with ciprofloxacin were able to divide in fresh medium, but the cell shape became significantly smaller than the strain untreated. Furthermore, expression of lon in the lon-unexpressed cells at 24 hours after treatment with ciprofloxacin led to detect the number of colonies similar to the wild-type. These findings together, it is suggested that Lon protease could regulate awakening from ciprofloxacin-induced persistence rather than the formation of persisters.