Pharmacogenomic strategies against microbial resistance: from bright to bleak to innovative.
The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is revealing new antimicrobial peptides and is applying old drugs in new ways to break resistance. New approaches with host-directed drug targeting emerge to circumvent resistance. A future systems perspective from large-scale molecular techniques and bioinformatic modeling allows pharmacogenomics to reveal new intervention angles. This includes the fight against resistance and its transmission, improved vaccines, disarmament of microbes and antibiotic options from novel molecular targets (lipids, RNA and carbohydrates). Such a system perspective is also essential for improved diagnostics and individualized medicine. However, an increase in public awareness and closer cooperation of industry and basic research are essential to turn research into powerful new drugs that will enable us to treat new arising infections in the future.
Dandekar
Thomas
T
Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. dandekar@biozentrum.uni-wuerzburg.de
Dandekar
Gudrun
G
D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000235:genetics; D019295:Computational Biology; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004352:Drug Resistance, Microbial / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D005544:Forecasting; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006095:Gram-Positive Cocci / Q000187:drug effects; D006801:Humans; D000069349:Linezolid; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000379:methods* / Q000639:trends; D049490:Systems Biology; D000078304:Tigecycline; D014769:Virginiamycin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014769:Virginiamycin; C113825:quinupristin; D000078304:Tigecycline; D008911:Minocycline; D000069349:Linezolid; D017576:Daptomycin