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Forward Genetic Screening Identifies a Small Molecule That Blocks Growth by Inhibiting Both Host- and Parasite-Encoded Kinases


Understanding how a compound blocks growth of an intracellular pathogen is important not only for developing these compounds into drugs that can be prescribed to patients, but also because these data will likely provide novel insight into the biology of these pathogens. Forward genetic screens are one established approach towards defining these mechanisms. But performing these screens with intracellular parasites has been limited not only because of technical limitations but also because the compounds may have off-target effects in either the host or parasite. Here, we report the first compound that kills a pathogen by simultaneously inhibiting distinct host- and parasite-encoded targets. Because developing drug resistance simultaneously to two targets is less likely, this work may highlight a new approach to antimicrobial drug discovery.


Vyšlo v časopise: Forward Genetic Screening Identifies a Small Molecule That Blocks Growth by Inhibiting Both Host- and Parasite-Encoded Kinases. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004180
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004180

Souhrn

Understanding how a compound blocks growth of an intracellular pathogen is important not only for developing these compounds into drugs that can be prescribed to patients, but also because these data will likely provide novel insight into the biology of these pathogens. Forward genetic screens are one established approach towards defining these mechanisms. But performing these screens with intracellular parasites has been limited not only because of technical limitations but also because the compounds may have off-target effects in either the host or parasite. Here, we report the first compound that kills a pathogen by simultaneously inhibiting distinct host- and parasite-encoded targets. Because developing drug resistance simultaneously to two targets is less likely, this work may highlight a new approach to antimicrobial drug discovery.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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