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MoLife Research Seminar

01/24/2017 MOLIFE RESEARCH SEMINAR: Prof. Dr. Sven Bergstroem

Tuesday, January 24, 2017 - 13:00
Lecture Hall of Research II

MoLife Research Seminar by:

Prof. Dr. Sven Bergström, Umeå University, Department of Molecular Biology, Schweden

Title of the talk:

Chemical genetics to investigate Chlamydia trachomatis biology and pathogenesis

Chlamydia trachomatis is a bacterial pathogen of humans that causes a common sexually transmitted disease as well as eye infections. It grows only inside cells of its host organism, within a parasitophorous vacuole termed the inclusion. Little is known, however, about what bacterial components and processes are important for C. trachomatis cellular infectivity. Using a visual screen for compounds that affects bacterial distribution within the chlamydial inclusion, we identified the inhibitor KSK120. As hypothesized, the altered bacterial distribution induced by KSK120 correlated with a block in C. trachomatis infectivity. Our data suggests that the compound targets the glucose-6-phosphate (G-6P) metabolism pathway of C. trachomatis, supporting previous indications that G-6P metabolism is critical for C. trachomatis infectivity. Thus, KSK120 may be a useful tool to study chlamydial glucose metabolism and has the potential to be used in the treatment of C. trachomatis infections. Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect Escherichia coli or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection. Bacterial replication and the generation of infectious progeny are the hallmarks of efficient pathogenesis for Chlamydia. In a recent study we describe a novel mechanism for Chlamydial attenuation, through the inhibition of a host cell signalling pathway. We show that inhibition of ERK signalling by small molecule inhibitors result in production of non-infectious Chlamydia progeny.  Thus, the 2-pyridone amide compounds were shown to inhibit ERK signalling and were an effective treatment of vaginal chlamydia infections in a murine model. The 2-pyridone amide ERK-inhibitors were non-toxic to host cells and present a novel treatment approach for intracellular infections.


Engström et al mBio 2014 Dec 30;6(1):e02304-14. doi: 10.1128/mBio.02304-14.A 2-pyridone-amide inhibitor targets the glucose metabolism pathway of Chlamydia trachomatis.

Engström et al  Int J Med Microbiol. 2015 May;305(3):378-82.

doi: 10.1016/j.ijmm.2015.02.007. Expansion of the Chlamydia trachomatis inclusion does not require bacterial replication

Good JA et al 2016, J Med Chem. 2016 Mar 10;59(5):2094-108. doi:10.1021/acs.jmedchem.5b01759. Thiazolino 2-pyridone amide inhibitors of Chlamydia trachomatis infectivity


Prof. Dr. Sven Bergström

Prof. Dr. Sven Bergström,

Umea University, Department of Molecular Biology, Schweden