Síntesis de los sideróforos amonabactinas, análogos, y conjugados con nanopartículas, fluoróforos y antibióticos. Evaluación como antimicrobianos y en la detección de patógenos

Abstract

The present work is divided into three chapters: Chapter I. It begins with an introduction that highlights the important role played by the fish farming sector in Galicia and the problem of bacterial infections. The mechanism of iron uptake by siderophores in bacteria is described, exposing its potential to develop new treatments against pathogenic organisms. In previous work carried out on Aeromonas salmonicida subsp. salmonicida it was identified that it produces two types of siderophores, acinetobactin and amonabactins, and FstB protein is the receptor for the first of them. Next, the work carried out on the total synthesis of the four natural amonabactins is detailed, which by means of the results of the siderophore activity carried out on A. salmonicida allowed to identify FstC as the protein receptor of amonabactins. Finally, the synthesis of four structural analogues is described, that allows establishing a series of structure-activity relationships between the siderophore and its receptor. Two of them were selected as candidates for subsequent conjugations with nanoparticles, fluorophores and antibiotics. Chapter II. Gold nanoparticles conjugated with siderophore ferrioxamine and an amonabactin analogue are prepared. Their evaluation as bacteria detection sensors did not show the expected color change of the conjugate when they were in contact with the bacteria. Additionally, a silver nanoparticle-amonabactin analogue conjugate is synthesized and its antimicrobial properties are studied. The results indicated that the functionalization with this siderophore did not produce an increase in the antimicrobial activity of said nanoparticles. The adhesion process of some bacteria to functionalized gold surfaces with siderophores is analysed by scanning electron microscopy (SEM). Chapter III. Various conjugates between fluorophores and the selected amonabactin analogues prepared in chapter I are synthesized, finding that the conjugate bearing sulforhodamine B fluorophore acts as a fluorescent probe against different species of the genus Aeromonas and Acinetobacter baumannii. Furthermore, this probe has great potential as a sensor in the detection of Aeromonas due to its ability to distinguish Aeromonas cells from other fish pathogenic bacteria. Finally, three conjugates of the amonabactin analog used in the previous probe are prepared with three different antibiotics following the so-called Trojan horse strategy. Their biological evaluation against various bacterial species showed that these conjugates did not present antimicrobial activity.