File:Ppat.1006805.g002 (1).jpg

English: (A) Ciprofloxacin-susceptible E. coli. The inner and outer membranes intrinsically protect the bacterium. Also depicted are the AcrAB-TolC efflux pump, porin, and DNA gyrase (or topoisomerase IV) interacting with the DNA nucleoid (in blue). Ciprofloxacin (green diamond) can diffuse through the membranes but also accesses the cell via porins. Ciprofloxacin forms a ternary complex with the topoisomerase bound to DNA, resulting in cell death. (B) Chromosomally encoded ciprofloxacin resistance mechanisms. Altered porin(s), mutant gyrase (and perhaps also topoisomerase IV), and increased numbers of AcrAB-TolC efflux pumps are shown. Ciprofloxacin access is reduced via alterations (deletion, down-regulation, or mutation) in porins. Ciprofloxacin that enters the cell can be removed through increased numbers of efflux pumps. Ciprofloxacin that reaches the mutant topoisomerase(s) is less effective against the mutant version of the enzyme than the drug-susceptible version shown in A. (C) Plasmid-borne ciprofloxacin resistance mechanisms. Plasmids can harbor genes encoding the ciprofloxacin efflux pumps QepA or OqxAB, the Qnr protein—which binds gyrase by mimicking B-form DNA—or Aac(6’)-Ib-cr, an aminoglycoside-modifying acetyltransferase that acetylates and inactivates ciprofloxacin. Aac(6’)-Ib-cr, aminoglycoside 6’-N-acetyltransferase type lb-cr; AcrAB-TolC, Acriflavin-resistant Proteins AB Tolerant to Colicin E mutant; OqxAB, olaquindox-resistant efflux pump proteins A and B; QepA, quinolone efflux pump A; Qnr, quinolone resistance protein.