95
Considering gene or reaction essentiality approach, if a gene knockout or alteration in reaction leads to effects in the surrounding network, the enzymes or protein
encoded by the altered node might be considered a drug target (Thiele et al. 2005;
Oberhardt et al. 2009). In one of the first metabolic reconstruction pathway analysis
of a pathogen (Schilling and Palsson 2000), Haemophilus influenzae gene essentiality analysis revealed 11 critical genes and six others under specific conditions.
Essentiality criteria might be used alone or associated with other approaches.
Moreover, essentiality can be restricted to a specific pathogen environment, where
conditions of growing and access to nutrients can drive a microorganism expression
profile.
Klebsiella pneumoniae is an opportunistic pathogen that has been responsible
for infection outbreaks in hospitals, being especially risk to adults under intensive
care and newborns (Podschun and Ullmann 1998). Extended spectrum β lactamases
enzymes are produced by different Klebsiella pneumoniae strains (Ramos et al.
2018). Through an integrative approach using genomics, transcriptomics,
Fig. 4.2 The workflow of metabolic network analysis. The figure represents an overview of metabolic network reconstruction and analysis for target identification
4 In Silico Approaches for Prioritizing Drug Targets in Pathogens
Considering gene or reaction essentiality approach, if a gene knockout or alteration in reaction leads to effects in the surrounding network, the enzymes or protein
encoded by the altered node might be considered a drug target (Thiele et al. 2005;
Oberhardt et al. 2009). In one of the first metabolic reconstruction pathway analysis
of a pathogen (Schilling and Palsson 2000), Haemophilus influenzae gene essentiality analysis revealed 11 critical genes and six others under specific conditions.
Essentiality criteria might be used alone or associated with other approaches.
Moreover, essentiality can be restricted to a specific pathogen environment, where
conditions of growing and access to nutrients can drive a microorganism expression
profile.
Klebsiella pneumoniae is an opportunistic pathogen that has been responsible
for infection outbreaks in hospitals, being especially risk to adults under intensive
care and newborns (Podschun and Ullmann 1998). Extended spectrum β lactamases
enzymes are produced by different Klebsiella pneumoniae strains (Ramos et al.
2018). Through an integrative approach using genomics, transcriptomics,
Fig. 4.2 The workflow of metabolic network analysis. The figure represents an overview of metabolic network reconstruction and analysis for target identification
4 In Silico Approaches for Prioritizing Drug Targets in Pathogens