Kronična pseudomonasna infekcija pluća oboljelih od cistične fibroze

master's thesis

• Title (english): Chronic pseudomonas lung infection in cystic fibrosis patients
• Author: Marcela Mendek
• Mentor: Jasmina Vraneš (mentor)
• Committee member: AMARELA LUKIĆ-GRLIĆ (predsjednik povjerenstva)
• Committee member: Goran Tešović (član povjerenstva)
• Committee member: Jasmina Vraneš (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Microbiology and Parasitology); Zagreb
• Defense date and country: 2018-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Medical Microbiology

Abstract

Cistična fibroza najčešća je autosomno recesivna nasljedna bolest u bijele rase. To je multisustavna bolest, uzrokovana mutacijom u genu koji kodira transmembranski regulator cistične fibroze (CFTR). Posljedica njegove disfunkcije je stvaranje je gustog, ljepljivog sekreta koji oblaže dišne puteve i onemogućava normalni mukocilijarni klirens. Dolazi do nakupljanja bakterija i razvoja infekcije. Pseudomonas aeruginosa je ubikvitarno prisutan oportunistički patogen, sa sposobnošću preživljenja u bolničkim uvjetima. Kolonizira dišne puteve većine pacijenata koji boluju od cistične fibroze već u ranoj dječjoj dobi. Ako se tada ne liječi agresivnom antibiotskom terapijom, akutne intermitentne infekcije prelaze u kroničnu infekciju, s postupnim propadanjem plućne funkcije, sve do respiratornog zatajenja. Tome doprinosi jaki polimorfonuklearni upalni odgovor, koji otpuštanjem kisikovih radikala, uzrokuje mutacije u genomu P. aeruginosa, i pojavu mukoidnog fenotipa obilježenog pojačanim stvaranjem polisaharida alginata i stvaranjem biofilma. Biofilm je nakupina bakterija uloženih u egzopolisaharidni matriks, unutar kojeg bakterije postaju slabije virulentne i metabolički aktivne te ostaju zaštićene od djelovanja imunološkog sustava domaćina i antibiotika. Na taj način, pseudomonas preživljava i perzistira u plućima oboljelih. Konvencionalna terapija kronične plućne infekcije je kronična supresivna terapija inhalacijskim antibioticima, s ciljem održavanja primjerene plućne funkcije. Zbog pojave visoke antibiotske rezistencije, razvoj lijekova usmjeren je prema novim formulacijama i kombinacijama antibiotika, te prema tvarima koje sprječavaju formiranje biofilma (inhibitori quorum sensing sustava, antioksidansi, kelatori željeza) ili uzrokuju njegovu razgradnju.

Abstract (english)

Among Caucasians, cystic fibrosis is the most common autosomal recessive inherited disease. It is a multisystem disease caused by a genetic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR). As a consequence, a thick mucus layer coating the surface of airway epithelium is formed, disabling normal mucocilliary clearance. Pseudomonas aeruginosa is an ubiquitous opportunistic pathogen, with the ability to survive in hospital environment. By early childhood, it colonizes the airways of most cystic fibrosis patients. If it is not promptly treated by aggressive antibiotic therapy at that stage, the acute intermittent infections become chronic, with a gradual decrease in pulmonary function leading to respiratory failure. This is perpetuated by a strong polimophonuclear inflammatory response, with production of oxygen radicals which cause mutations in Pa genome, and induce the mucoid phenotype, characterized by alginate overproduction and biofilm formation. Biofilm is a bacterial consortium, embedded in an exopolysaccharide matrix, within which the bacteria have reduced virulence and metabolic activity, but are protected against the activities of host immune system and the effects of antibiotic substances. This allows pseudomonas to survive and persist in the cystic fibrosis lung. Conventional chronic pulmonary infection therapy is chronic suppressive therapy, via inhaled antibiotics, with the primary goal of maintaining lung function in patients. Due to emergence of high antibiotic resistance, development of new drugs is focused on producing different antibiotic fomulations and combinations, and towards investigation of substances which can prevent biofilm formation (quorum sensing inhibitors, antioxidants, ion chelators), or achieve its disintegration.

• Keywords: cistična fibroza; Pseudomonas aeruginosa; kronična infekcija pluća; biofilm
• Keywords (english): cystic fibrosis; Pseudomonas aeruginosa; chronic lung infection; biofilm
• Language: croatian
• URN:NBN: urn:nbn:hr:105:103735
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-01-03 13:04:43