The decline of antibiotic era--new approaches for antibacterial drug discovery.
Infectious diseases still remain the main cause of human premature deaths; especially in developing countries. The emergence and spread of pathogenic bacteria resistant to many antibiotics (multidrug-resistant strains) have created the need for the development of novel therapeutic agents. Only two new classes of antibiotics of novel mechanisms of action (linezolid and daptomycin) have been introduced into the market during the last three decades. The recent progress in molecular biology and bacterial genome analysis has had an enormous impact on antibacterial drug research. This review presents new achievements in searching a new bacterial essential genes, a potential targets for antibacterial drugs. Application of metagenomics strategy is also shown. Some recent technologies aimed at development of anti-pathogenic drugs such as inhibitors of quorum sensing process or histidine kinases are also discussed. Extensive research efforts have provided many details concerning structure of bacterial proteins playing an important role in pathogenesis such as adherence proteins or toxins, what allowed searching for antitoxin drugs or drugs interfering with bacterial adhesion. As an example, the review focuses on anthrax therapies under development. Additionally, the article presents the progress in phage therapy; using bacteriophages or their products such as lysins in antibacterial therapy.
Jagusztyn-Krynicka
Elzbieta K
EK
Faculty of Biology, Institute of Microbiology, Department of Bacterial Genetics, University of Warsaw, Warsaw, Poland. kjkryn@biol.uw.edu.pl
Wyszyńska
Agnieszka
A
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000737:chemistry; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D001422:Bacterial Adhesion; D001427:Bacterial Toxins / Q000737:chemistry; D001435:Bacteriophages / Q000737:chemistry; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D023281:Genomics; D011487:Protein Conformation; D053038:Quorum Sensing; D015398:Signal Transduction
D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D000581:Amidohydrolases; C084507:peptide deformylase