Write a research paper about the evolutionary effects of fluoroquinolone resistance.1) What is your approved topic?
2) What are the references you will use for this? Three minimum.
3) Establish your outline according to this example, this is just one style of an outline:
Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success
Broad Overview
Target-site gene mutations
Increased production of multidrug-resistance efflux pumps
Modifying enzymes
Target-protection proteins
quinolone/fluoroquinolone antibiotics treat many infections
Resistance to agents are combination of
Impacts of quinolone-resistance mutations in relation to fitness/evolutionary success of mutant strains
Challenge of Fluoroquinolone resistance
Pressing global concern in medicine bc highly resistant pathogens
Few drugs in development
Quinolones and fluroquinolones
Differ from quinoles by replacement of 8th C w/ N and addition of F at 6th position
Correlation between increased usage of fluoroquinoles and increased resistance of bacteria
Current prescribed: ciprofloxacin, levofloxacin, moxifloxacin
Fluoroquinolones: normal antibiotics used since 1980s
Supercoiling and type II topoisomerase
Fluroquinolones- potential inhibitor of bacterial type II topoisomerase
Mechanisms of fluoroquinolone action
Impaired DNA replication
Gram (-) bacteria target is DNA gyrase
Gram (+) bacteria topoisomerase IV is preferentially targeted
Target DNA gyrase/topoisomerase IV thereby inhibiting control of supercoiling
Fluoroquinolone-resistance mechanisms
QRDR from amino acid sub alter protein structure
Encoded on plasmids PMQR genes
Binding of Qnr protein which physically prevents antibody to topoisomerase
Double-membrane structure, gram-negative cell wall presents barrier
Chromosomal multidrug efflux pumps remove antibodies
Target-site mutation
Transmissible quinolone-resistance mechanisms
Membrane permeability
Efflux
Evolutionary consequences of fluoroquinolone resistance
Mutation in gryA increase fitness / can out-compete wild type strains
Single point mutations affect fitness more than combinations of mutations
Conclusion
Certain strains have fitness advantage over other antibiotic-sensitive strains
Strains continue and pass resistance even if drug use decreases
Fluoroquinolone resistance can be selected (many different strains)
