Abstract
Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections globally and is one of the most commonly reported infections in the United States. There is a need to develop new therapeutics due to drug resistance and the failure of current treatments to clear persistent infections. Structures of potential C. trachomatis rational drug-discovery targets, including C. trachomatis inorganic pyrophosphatase (CtPPase), have been determined bythe Seattle Structural Genomics Center for Infectious Disease. Inorganic pyrophosphatase hydrolyzes inorganic pyrophosphate during metabolism. Furthermore, bacterial inorganic pyrophosphatases have shown promise for therapeutic discovery. Here, a 2.2 Å resolution X-ray structure of CtPPase is reported. The crystal structure of CtPPase reveals shared structural features that may facilitate the repurposing of inhibitors identified for bacterial inorganic pyrophosphatases as starting points for new therapeutics for C. trachomatis.
Highlights
Chlamydiae are obligate intracellular bacteria that infect a wide range of eukaryotes, including humans, animals, insects and free-living amoebae
Reinfection is common with all antibiotics, and compliance is low for doxycycline (Centers for Disease Control and Prevention, 2021)
Expression and purification were conducted as part of the Seattle Structural Genomics Center for Infectious Disease (SSGCID) following standard protocols described previously (Bryan et al, 2011; Choi et al, 2011; Serbzhinskiy et al, 2015)
Summary
Chlamydiae are obligate intracellular bacteria that infect a wide range of eukaryotes, including humans, animals, insects and free-living amoebae. Chronic chlamydia infection often leads to genital, ocular and respiratory disease (Lorenzini et al, 2010). Genital chlamydia is a major public health concern, with over 1.8 million cases reported to the US Centers for Disease Control and Prevention (CDC) in 2019. Chlamydia is the most common bacterial sexually transmitted infection globally and is a leading cause of infertility (van Bergen et al, 2021; Dombrowski, 2021). The CDC recommends treating chlamydia in adults and adolescents with 100 mg doxycycline orally twice a day for seven days. Reinfection is common with all antibiotics, and compliance is low for doxycycline (Centers for Disease Control and Prevention, 2021). Efforts to identify new treatment strategies for chlamydia at the Seattle Structural Genomics Center for Infectious Disease (SSGCID) include structural studies of C. trachomatis proteins as the first steps towards rational drug discovery
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