Nove strategije u istraživanjima i razvoju antimikrobnih lijekova

master's thesis

• Title (english): New Strategies in Research and Development of Antimicrobial Drugs
• Author: Laura Pašalić
• Mentor: Jelena Šuran (mentor)
• Committee member: Frane Božić (predsjednik povjerenstva)
• Committee member: Ozren Smolec (član povjerenstva)
• Committee member: Jelena Šuran (član povjerenstva)
• Granter: University of Zagreb; Faculty of Veterinary Medicine; (Department of Pharmacology and Toxicology); Zagreb
• Defense date and country: 2019-07-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Veterinary Medicine; Veterinary Public Health and Food Safety

Abstract

Antibiotici su, od otkrića u 20. st., postali najznačajniji lijekovi u povijesti medicine. Između 1940. i 1962. na tržište je izbačeno više od 20 novih vrsta antibiotika. Od tada su na tržište dospjele samo dvije nove skupine lijekova. Već prvi otkriveni antibiotik, penicilin, ostvario je značajan uspjeh. Bakteriolog Alexander Fleming već je tada predvidio nastanak rezistencije na penicilin, a rezistencija se razvila i prema kasnije nastalim antibioticima. Danas rezistencija predstvalja globalni javnozdravstveni problem. Rezistencija znatno ugrožava ljudsko zdravlje. Godišnje umre oko 33 000 ljudi uslijed infekcija uzrokovanih rezistentnim bakterijama. Sve veći izazov antimikrobne rezistencije i nedostatak novih antibiotika, naglašavaju važnost razvoja novih terapija.
Rezistencija u bakterija može nastati promjenama u genomu i unosom vanjske DNA. Poznato je da veterinarska medicina znatno doprinosi nastanku rezistencije, budući da se antibiotici u životinja koriste kao promotori rasta. To je dovelo do potrebe za razvojem novih pristupa u liječenju bakterijskih infekcija. Jedan od obećavajućih pristupa je djelovanje na specifične faktore virulencije, tj. na sustave međustanične komunikacije. Veliki potencijal je pokazalo djelovanje na bakterijski QS. To je sposobnost otkrivanja i odgovaranja na gustoću stanične populacije putem regulacije gena. Nadalje, antimikrobni peptidi (AMP) su dobili veliku pozornost kao nova skupina lijekova. To su peptidni antibiotici koje karakterizira amfipatska priroda izvedena iz njihovih pozitivnih naboja i hidrofobnih aminokiselinskih ostataka. Osim sredstava koja djeluju na bakterije, istraživanja su usmjerena i na poboljšanje imunološkog sustava domaćina. Trenutno, najveći potencijal kao alternativa antibioticima pokazuju cjepiva i protutijela te bakteriofagi.
Za otkrivanje najboljeg načina liječenja bakterijskih infekcija, trebaju se provesti ispitivanja antimikrobne osjetljivosti i utemeljiti koja vrsta bakterije uzrokuje bolest. Budući da rezistencija bakterija na antibiotike nije jedini problem, već i nedovoljan razvitak novih antibiotika, udruženje informacija i spoznaja s dosada provedenih istraživanja, moglo bi dovesti do pronalska novih vrsta antibiotika.

Abstract (english)

Antibiotics, from their discoveries in the 20th century, have become the most important drugs in the history of medicine. Between 1940. and 1962., more than 20 new classes of antibiotics were marketed. Since then, only two new drug classes have reached the market. The first discovered antibiotic, penicilin, has achieved significant success. During his research, Fleming already predicted emergence of resistance to penicilin, and resistance also developed to subsequent antibiotics. Today, resistance apperas to be a global public health issue. Resistance significantly endangers human health. About 33 000 people die every year due to infections caused by resistant bacteria. The growing challenge of antimicrobial resistance and the paucity of novel antibiotics underscore the importance of developing novel therapeutics.
Resistance to bacteria can be caused by changes in the genome or by the intake of external DNA. It is well known that veterinary medicine contributes significantly to the emergence of resistance, since antibiotics in animals are used as growth promoters. This has led to the need of developing new approaches to the treatment of bacterial infections. One of the promising approaches is targeting a specific virulence factors, i.e. intercellular comunication systems. Targeting bacterial QS has shown a great potential. Quorum sensing is the ability to detect and to respond to cell population density by gene regulation. Futhermore, AMPs received great attention as a new drug class. These are peptide antibiotics characterized by amphipatic nature derived from their positive charges and hydrophobic amino acid residues. In addition to agents that act on bacteria, the research is also focused on improving the immune system of the host. At present, the greatest potential as an alternative to antibiotics have vaccines, antibodies and bacteriophages.
To detect the best way to treat bacterial infections, antimicrobial sensitivity test should be conducted and the type of bacteria that causes the disease to be determined. Since bacterial resistance to antibiotics is not the only issue, but the insufficient development of new antibiotics, the information and knowledge by so far conducted researches could lead to discovery of new drug classes.

• Keywords: antimikrobni lijekovi; bakterijske infekcije; rezistencija
• Keywords (english): antimicrobial drugs; bacterial infections; resistance
• Language: croatian
• URN:NBN: urn:nbn:hr:178:319397
• Study programme: Title: Veterinary Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica veterinarske medicine (doktor/doktorica veterinarske medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-01-28 10:28:04