Study of the Lysogenic Phages and Their Potential Applications in Clinical Strains of Multi-Drug Resistant Bacteria

Abstract

Bacteria with multiple resistance entail a global threat. In recent years, phage therapy has been widely reconsidered as an alternative to antibiotics. In particular, lytic phages have been shown to have great potential for treating infections with multi-resistant bacteria. In this thesis, we present the utility and study of lysogenic phages in clinical strains of multi-resistant bacteria. Concerning the potential of lysogenic phages in phage therapy, we have developed the strategy of transforming a lysogenic phage into a lytic one, Ab105-2φΔCI, and characterized its microbial activity. We also have purified and assayed the antimicrobial activity of two endolysins ElyA1 and ElyA2, from two prophages of a clinical strain of A. baumannii. Both alternatives have been shown to be effective in combination with antibiotics. In relation to the study of lysogenic phages in clinical strains, we pointed out the problem of the possible appearance of bacterial resistance against phages and the importance of searching and characterizing these resistance systems by searching in silico for phage resistance mechanisms in clinical strains of A. baumannii. We also identified 4 complete prophages in clinical strains of P. aeruginosa, 2 of them were newly identified: a Siphovirus phage, AUS531phi, and a filamentous Inovirus phage, pf8. Furthermore, we characterized a gene that increases the ability of one of them, the bci gene in AUS531phi, to infect the bacteria by the regulation of the Quorum system.