Novel strategies to combat gram-negative bacterial pathogens using bacteriophage proteins ; Novas estratégias para combater bactérias patogénicas gram-negativas usando proteínas bacteriofágicas

Dissertação de mestrado em Bioengenharia ; The infections caused by Gram-negative pathogens are a concern to global health, resulting in high rates of morbidity, mortality and high costs in health care. Once formed, biofilms cause reduction of host defenses and increase resistance to antimicrobial products 10 to 1000 times more than the cells in their planktonic state. According to recent studies, in 2050, bacterial infections, associated with the growing resistance of pathogens to antimicrobial agents, will cause more than 300 million premature deaths and a loss of € 90 trillion to the global economy. At this scenario is extremely important the research and the development of new methodologies to eliminating bacteria and prevent or eradicate biofilm formation. The use of phage proteins presents several advantages as a potential alternative to antibiotics, since they are natural products with a low environmental impact and able to reduce aggregation and bacterial growth. The aim of this project was to select and study the use of phage proteins to treat three Gram-negative bacteria: Pseudomonas, Salmonella and Escherichia. From the 18 proteins studied, 10 were expressed and these 4 had positive results. The holin from phage Lambda and the spanin Rz from phage T1 eliminated, with efficiency, planktonic cells of ATCC 10145 and protein T1_146 showed to be effective when applied to PAO1 planktonic cells. Biofilms of BL21 were effectively removed by Alginate Lyase. The results showed the studied phage protein present high potential in the control of Gram-negative bacteria turning them an important alternative to antibiotics in the treatment of infection caused by these bacteria. ; As infeções causadas por bactérias patogénicas Gram-negativas são uma preocupação para a saúde global, resultando em taxas elevadas de morbidade, mortalidade e em altos custos em cuidados de saúde. Os biofilmes bacterianos provocam a redução das defesas do hospedeiro e o aumento da resistência a produtos antimicrobianos entre 10 a 1000 vezes ...