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| Project leader |
Barisic Lidija |
| Project co-leader: |
Lidija Barišić, Predrag Čudić |
| Administering organization: |
Faculty of Food Technology and Biotechnology, University of Zagreb, Croatia |
| Partner Institution/Company: |
Florida Atlantic University |
| Grant type: |
2A |
| Project title: |
Antibiotic plusbacin A3: total solid-phase synthesis and structure-activity relationship study |
| Project summary: |
Due to the wide spread use of broad spectrum antibiotics, bacterial resistance has been increasing rapidly in recent years presenting a serious threat to public health. For the last thirty years the antibiotic vancomycin has been the last line of defense against bacterial strains that are resistant to most of other antibiotics. As bacteria progressively become resistant to front line antimicrobial agents our capacity to effectively treat bacterial infections will be severely hindered. Therefore, identifying novel antibacterial targets and new antibacterial chemotherapeutics capable of treating infections from drug-resistant microorganisms is of vital importance. Drugs with different modes of action from vancomycin could be promising candidates against vancomycin-resistant strains. Promising candidate for reverting multi-drug resistant bacteria is naturally occurring cyclic depsipeptide antibiotic plusbacin A3 which exhibits strong activity against various Gram-positive bacteria, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE), two important human pathogens. This research proposal describes the total solid-phase synthesis, antibacterial and hemolytic activity, and characterization of the plusbacin A3 complex with bacterial cell wall precursor lipid II. Completion of this research will provide a clear picture of plusbacin’s A3 mode of action and pave the way for the design and synthesis of new and more potent antibiotics. |
| Hrvatski sažetak: |
Zbog velike upotrebe širokog spektra antibiotika, dolazi do rapidnog porasta bakterijske rezistencije što predstavlja ozbiljnu prijetnju za ljudsko zdravlje. U zadnjih trideset godina, antibiotik vankomicin predstavlja zadnju liniju obrane prema bakterijama rezistentnim na većinu drugih antibiotika. Kako se rezsitencija na antimikrobne agense progresivno razvija, mogućnosti učinkovitog tretiranja bakterijskih infekcija su ozbiljno ugrožene. Zbog toga je od vitalnog interesa identifikacija novih antibakterijskih meta i novih antibakterijskih kemoterapeutika djelotvornih protiv mikroorganizama otpornih na lijekove. Lijekovi drugačijeg načina djelovanja u odnosu na vankomicin mogli bi biti obećavajući kandidati za tretman sojeva rezistentnih na vankomicin. Takav je antibiotik prirodni ciklički depsipeptid plusbacin A3 koji je visokodjelotvoran protiv različitih Gram-pozitivnih bakterija, uključujući meticilin-rezistentni S. aureus (MRSA) i vankomicin-rezistentni enterokok (VRA), dva najvažnija humana patogena. Ovaj projekt uključuje sintezu na čvrstoj fazi, antibakterijsku i hemolitičku aktivnost i karakterizaciju kompleksa plusbacina A3 s prekursorom lipida II iz stanične stijenke. Dovršenjem ovog projekta dobit će se jasna slika načina djelovanja plusbacina A3 i trasirat će se put za sintezu novih i moćnijih antibiotika. |
| Amount requested from UKF: |
10.000 € |
| Amount of matching funding: |
32.000 € |
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