OBJECTIVES: To confirm and better understand the deleterious effect of fluoroquinolones reported during Rickettsia conorii infection in humans. METHODS: We used a new plaque assay to test the effect of ciprofloxacin on cells infected by R. conorii. Controls were mock-treated infected cells and infected cells treated with doxycycline. We used real-time quantitative RT-PCR to quantify vapC and vapB transcripts in cells infected by R. conorii treated with ciprofloxacin or mock treated. RESULTS: By plaque assay, at baseline (0 h) there is no difference in lytic area between cells treated with ciprofloxacin (whatever concentration used) and controls. Ciprofloxacin at 0.5 and 50 mg/L induced a significant increase in lytic areas compared with the control at 2 h, 4 h, 6 h (P<0.0001) and 24 h (P<0.0001 and P=0.035, respectively) when not induced with doxycycline. By real-time quantitative RT-PCR, ciprofloxacin was found to cause an up-regulation of toxin-antitoxin (TA) module transcription. Indeed, the mRNA levels of vapC and vapB were significantly increased at 2 h and 4 h in cells treated with 50 mg/L ciprofloxacin (not with 0.5 mg/L ciprofloxacin) compared with control levels (fold change >2.9). CONCLUSIONS: These in vitro findings correlated with our previous clinical findings: fluoroquinolones have a deleterious effect during R. conorii infection, not found with doxycycline. We speculate that the toxic effect of fluoroquinolones on R. conorii-infected cells is mediated by the overexpression of TA, possibly followed by their release into the host cytoplasm as described in Rickettsia felis.
OBJECTIVES: To confirm and better understand the deleterious effect of fluoroquinolones reported during Rickettsia conorii infection in humans. METHODS: We used a new plaque assay to test the effect of ciprofloxacin on cells infected by R. conorii. Controls were mock-treated infected cells and infected cells treated with doxycycline. We used real-time quantitative RT-PCR to quantify vapC and vapB transcripts in cells infected by R. conorii treated with ciprofloxacin or mock treated. RESULTS: By plaque assay, at baseline (0 h) there is no difference in lytic area between cells treated with ciprofloxacin (whatever concentration used) and controls. Ciprofloxacin at 0.5 and 50 mg/L induced a significant increase in lytic areas compared with the control at 2 h, 4 h, 6 h (P<0.0001) and 24 h (P<0.0001 and P=0.035, respectively) when not induced with doxycycline. By real-time quantitative RT-PCR, ciprofloxacin was found to cause an up-regulation of toxin-antitoxin (TA) module transcription. Indeed, the mRNA levels of vapC and vapB were significantly increased at 2 h and 4 h in cells treated with 50 mg/L ciprofloxacin (not with 0.5 mg/L ciprofloxacin) compared with control levels (fold change >2.9). CONCLUSIONS: These in vitro findings correlated with our previous clinical findings: fluoroquinolones have a deleterious effect during R. conorii infection, not found with doxycycline. We speculate that the toxic effect of fluoroquinolones on R. conorii-infected cells is mediated by the overexpression of TA, possibly followed by their release into the host cytoplasm as described in Rickettsia felis.
Authors: Philippe Parola; Christopher D Paddock; Cristina Socolovschi; Marcelo B Labruna; Oleg Mediannikov; Tahar Kernif; Mohammad Yazid Abdad; John Stenos; Idir Bitam; Pierre-Edouard Fournier; Didier Raoult Journal: Clin Microbiol Rev Date: 2013-10 Impact factor: 26.132
Authors: Hema P Narra; Abha Sahni; Jessica Alsing; Casey L C Schroeder; George Golovko; Anna M Nia; Yuriy Fofanov; Kamil Khanipov; Sanjeev K Sahni Journal: BMC Genomics Date: 2020-09-25 Impact factor: 3.969