Infrared spectroscopy for antibiotic discovery

Abstract

While the ‘war’ on infectious diseases has been considered won, antibiotic-resistant bacteria are currently responsible for 25,000 death’s yearly in Europe, bearing a predicted cost of €1.5 billion. Incidence of health-care associated infections in the United States of America is estimated at 1.7 million per year. No new broad-spectrum antibiotic has been introduced since the 1960s and as of 2011 only 2 agents are in Phase III clinical trials. As the antibiotic pipeline is clearly exhausted, new antibiotics are urgently needed. The present work evaluates Fourier Transform InfraRed Spectroscopy (FTIRS) as the basis of a novel Antibiotic Drug Discovery (ADD) platform. Initially the historical development of antibiotics was presented to contextualize the reader with the state-of-the-art. Resistance was discussed to bridge its upsurge and exhausted ADD platforms. Followed an objective review of infrared spectroscopy’s core concepts, its equipment developments alongside various applications for microbiological studies, the pharmaceutical and food industries besides diagnosis of several diseases. A high-throughput macro-cultivation protocol was adapted to determine minimum inhibitory concentrations of 14 antibiotics on an Escherichia coli model organism, while simultaneously building a spectral library. In order to comprehensively analyze such library a graphic user interface was constructed and used throughout this research. This allowed fair comparison of different pre-processing strategies on two alternative multivariate analysis algorithms, from which an optimal model was created for each proposed objective, in the context of an ADD platform. While some models were short of their objective, overall results were rather positive and suggest, alongside reviewed literature, that FTIRS could, and should, potentiate a new generation of antibacterial drug discovery platform that outperforms current alternatives.

Date of Award	8 Sept 2014
Original language	English
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Cecília R.C. Calado (Supervisor)