A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis

A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis

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ABSTRACT In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120.A fluorescent KSK120 analogue was synthesized and observed to be associated with the C.trachomatis surface, suggesting that its target is bacterial.

We isolated 3282770208962 KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P).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.IMPORTANCE 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.

Here, by using a visual screen for compounds that affect 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 suggest 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 caneta clareadora dental metabolism and has the potential to be used in the treatment of C.trachomatis infections.