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 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 south shore axess desk 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 rme ufx iii 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 metabolism and has the potential to be used in the treatment of C.trachomatis infections.