Journal
FEMS MICROBIOLOGY LETTERS
Volume 365, Issue 13, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/femsle/fny134
Keywords
ciprofloxacin; antibiotic resistance; Pseudomonas aeruginosa; Proteomic; DNA Gyrase; GyrA
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Funding
- BBSRC [BB/C500252/1, BB/M019411/1]
- BBSRC [BB/M019411/1] Funding Source: UKRI
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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.
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