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Authors: da Silva, Fabricio Alves Barbosa and Filho, Fernando Medeiros and Merigueti, Thiago Castanheira and Giannini, Thiago and Brum, Rafaela and de Faria, Laura Machado and do Nascimento, Ana Paula Barbosa and Belloze, Kele Teixeira and Silva, Floriano Paes and Albano, Rodolpho Mattos and dos Santos, Marcelo Trindade and de Castro, Maria Clicia Stelling and de Menezes, Marcio Argollo and Carvalho-Assef, Ana Paula D'A.

Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology, and computational approaches have been increasingly employed to tackle this task. In this chapter, we describe current efforts by FIOCRUZ and partners to develop integrated computational models of multidrug-resistant bacteria. The bacterium chosen as the main focus of this effort is Pseudomonas aeruginosa, an opportunistic pathogen associated with a broad spectrum of infections in humans. Nowadays, P. aeruginosa is one of the main problems of healthcare-associated infections (HAI) in the world, because of its great capacity of survival in hospital environments and its intrinsic resistance to many antibiotics. Our overall research objective is to use integrated computational models to accurately predict a wide range of observable cellular behaviors of multidrug-resistant P. aeruginosa CCBH4851, which is a strain belonging to the clone ST277, endemic in Brazil. In this chapter, after a brief introduction to P. aeruginosa biology, we discuss the construction of metabolic and gene regulatory networks of P. aeruginosa CCBH 4851 from its genome. We also illustrate how these networks can be integrated into a single model, and we discuss methods for identifying potential therapeutic targets through integrated models.

Journal:
DOI: 10.1007/978-3-319-74974-7_11
Year: 2018

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