Abstract
Ciprofloxacin is one of the most widely-used antibiotics, and has proven especially effective at controlling infections associated with the opportunistic human pathogen, Pseudomonas aeruginosa. In this work, we show that sub-inhibitory concentrations of ciprofloxacin induce discrete changes in the intracellular proteome. Central metabolism and cell envelope-associated functions are particularly affected. In spite of the low magnitude of the intracellular proteomic changes, we found that sub-lethal concentrations of ciprofloxacin had substantial effects on motility and exoprotein secretion. Crucially, the proteomic and phenotypic modulations that we observed were absolutely dependent upon the presence of wild-type GyrA; an isogenic strain of P. aeruginosa carrying a ciprofloxacin-insensitive form of GyrA (a T83→I mutant) did not display ciprofloxacin-dependent changes unless complemented with wild-type gyrA in trans. These results show that the diverse effects of sub-inhibitory ciprofloxacin on the cell are routed through its primary target in the cell, DNA gyrase.
References
Jun 1, 1990·Antimicrobial Agents and Chemotherapy·H YoshidaS Nakamura
Apr 1, 1983·Antimicrobial Agents and Chemotherapy·R WiseL J Edwards
Oct 11, 1994·Gene·S E WestL J Runyen-Janecky
Aug 1, 1996·Molecular Microbiology·K PooleT Nishino
Mar 16, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·D C Hooper
Aug 16, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·David C. Hooper
Mar 4, 2005·Proteomics·Natasha A KarpKathryn S Lilley
Jul 29, 2005·Antimicrobial Agents and Chemotherapy·Michelle D Brazas, Robert E W Hancock
Jul 29, 2005·Antimicrobial Agents and Chemotherapy·Ewa Ołdak, Elzbieta A Trafny
Sep 1, 2006·Current Opinion in Microbiology·Julian DaviesGrace Yim
Sep 7, 2007·Cell·Michael A KohanskiJames J Collins
May 14, 2008·Antimicrobial Agents and Chemotherapy·Katy JeannotPatrick Plésiat
Apr 9, 2010·Journal of Proteome Research·Hannah G SticklandMartin Welch
Jan 1, 2009·Microbial Biotechnology·Anna FàbregaJordi Vila
May 17, 2017·Biophysics Reviews·Charles J Dorman, Matthew J Dorman
Citations
May 12, 2019·Antibiotics·Franziska KampshoffDebarun Dutta
Dec 19, 2019·Veterinary World·A N DapghE A Elgabry
Sep 6, 2018·FEMS Microbiology Letters·Craig Winstanley, Kendra P Rumbaugh
Nov 24, 2020·Advances in Pharmacological and Pharmaceutical Sciences·Tafadzwa ChipenziStanley Mukanganyama
Sep 30, 2021·Archives of Microbiology·Aarti S KakatkarRavindranath Shashidhar