91
parasite illnesses are prevalent in developing countries where the population suffers
from malnutrition and have poor access to clean water and proper sanitation, factors
that result in a debilitated immune system (Secor et al. 2015).
Malaria is a parasitic disease caused mainly by Plasmodium falciparum and
P. vivax. The parasite is transmitted by Anopheles mosquito and initially infects
erythrocytes and once into the bloodstream, in severe cases can reach the brain leading to cerebral malaria. The treatment is centred on artemisinin based combination
therapies with an overall efficacy rate of 95% with described multi drug resistance
parasites observed in the Cambodia Thailand border (Secor et al. 2015). The spread
of resistant strains to other parts of the world could pose a major public health challenge and jeopardize important recent gains in malaria control. In 2017, 219 million
cases of malaria were reported with 435,000 deaths worldwide (WHO, 2018b).
Approximately 70% of the reported cases were concentrated in Africa and India. A
newly experimental vaccine shown partial protection against P. falciparum in children and was recommended by WHO for a pilot introduction in Ghana, Malawi, and
Kenya. This new strategy may decrease the anti parasitic resistant problem and the
overall burden of the disease.
Bearing the obstacles generated by the use of antimicrobials, the prevention of
further antimicrobial resistant community spread, and the inhibition of the propagation of pathogens are of utmost importance and require synergistic, overlapping,
and complementing approaches. There is no single solution and a multi-disciplinary
tactic is the best trail to guarantee and endure access to effective antimicrobial
therapies.
The search for alternative treatment (e.g. antimicrobial compounds, bacteriophages and phage associated enzymes, and alternative drug targets) denotes a viable
option to replace antimicrobials as the main source of treatment (Bragg et al. 2018).
Targeted drug development retains major challenges from candidate selection to in
vitro and in vivo experiments and clinical trials. Yet, the advances in scientific
knowledge (i.e. disease and pathogen) and research and development, the advent of
omics approaches (e.g. genomics, transcriptomics, and proteomics), and bioinformatics breakthroughs conduct to a ‘big data era’ that improved identification of
putative targets via the application of in silico tools that shortened the timeline in a
cost efficient manner (Bruno et al. 2017). In this chapter, we are focusing on different bioinformatics strategies for prioritizing drug targets in pathogens.
4.7 Post Genomics Era and Prioritization of Drug Targets
High throughput techniques in genome sequencing have provided an increasing
number of putative drug targets to microbial, directing the efforts on how to diminish molecular targets that should be tested experimentally. Currently, comparative
genomics associated with pan-genomics, subtractive genomics, structural bioinformatics, and metabolic pathways analysis approaches are applied to reach the development of new antibiotics and fight antimicrobial resistance.
4 In Silico Approaches for Prioritizing Drug Targets in Pathogens
parasite illnesses are prevalent in developing countries where the population suffers
from malnutrition and have poor access to clean water and proper sanitation, factors
that result in a debilitated immune system (Secor et al. 2015).
Malaria is a parasitic disease caused mainly by Plasmodium falciparum and
P. vivax. The parasite is transmitted by Anopheles mosquito and initially infects
erythrocytes and once into the bloodstream, in severe cases can reach the brain leading to cerebral malaria. The treatment is centred on artemisinin based combination
therapies with an overall efficacy rate of 95% with described multi drug resistance
parasites observed in the Cambodia Thailand border (Secor et al. 2015). The spread
of resistant strains to other parts of the world could pose a major public health challenge and jeopardize important recent gains in malaria control. In 2017, 219 million
cases of malaria were reported with 435,000 deaths worldwide (WHO, 2018b).
Approximately 70% of the reported cases were concentrated in Africa and India. A
newly experimental vaccine shown partial protection against P. falciparum in children and was recommended by WHO for a pilot introduction in Ghana, Malawi, and
Kenya. This new strategy may decrease the anti parasitic resistant problem and the
overall burden of the disease.
Bearing the obstacles generated by the use of antimicrobials, the prevention of
further antimicrobial resistant community spread, and the inhibition of the propagation of pathogens are of utmost importance and require synergistic, overlapping,
and complementing approaches. There is no single solution and a multi-disciplinary
tactic is the best trail to guarantee and endure access to effective antimicrobial
therapies.
The search for alternative treatment (e.g. antimicrobial compounds, bacteriophages and phage associated enzymes, and alternative drug targets) denotes a viable
option to replace antimicrobials as the main source of treatment (Bragg et al. 2018).
Targeted drug development retains major challenges from candidate selection to in
vitro and in vivo experiments and clinical trials. Yet, the advances in scientific
knowledge (i.e. disease and pathogen) and research and development, the advent of
omics approaches (e.g. genomics, transcriptomics, and proteomics), and bioinformatics breakthroughs conduct to a ‘big data era’ that improved identification of
putative targets via the application of in silico tools that shortened the timeline in a
cost efficient manner (Bruno et al. 2017). In this chapter, we are focusing on different bioinformatics strategies for prioritizing drug targets in pathogens.
4.7 Post Genomics Era and Prioritization of Drug Targets
High throughput techniques in genome sequencing have provided an increasing
number of putative drug targets to microbial, directing the efforts on how to diminish molecular targets that should be tested experimentally. Currently, comparative
genomics associated with pan-genomics, subtractive genomics, structural bioinformatics, and metabolic pathways analysis approaches are applied to reach the development of new antibiotics and fight antimicrobial resistance.
4 In Silico Approaches for Prioritizing Drug Targets in Pathogens