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A 2-Pyridone-Amide ...
A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis
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- Engström, Patrik (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR)
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- Krishnan, K. Syam (author)
- Umeå universitet,Umeå Centre for Microbial Research (UCMR),Kemiska institutionen
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Ngyuen, Bidong D. (author)
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- Chorell, Erik (author)
- Umeå universitet,Umeå Centre for Microbial Research (UCMR),Kemiska institutionen
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- Normark, Johan (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR)
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- Silver, Jim (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)
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Bastidas, Robert J. (author)
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Welch, Matthew D. (author)
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Hultgren, Scott J. (author)
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- Wolf-Watz, Hans (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR)
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Valdivia, Raphael H. (author)
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- Almqvist, Fredrik (author)
- Umeå universitet,Umeå Centre for Microbial Research (UCMR),Kemiska institutionen
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- Bergström, Sven (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR)
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(creator_code:org_t)
- 2015
- 2015
- English.
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In: mBio. - 2161-2129 .- 2150-7511. ; 6:1
- Related links:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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 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 metabolism and has the potential to be used in the treatment of C. trachomatis infections.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Engström, Patrik
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Krishnan, K. Sya ...
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Ngyuen, Bidong D ...
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Chorell, Erik
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Normark, Johan
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Silver, Jim
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Bastidas, Robert ...
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Welch, Matthew D ...
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Hultgren, Scott ...
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Wolf-Watz, Hans
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Valdivia, Raphae ...
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Almqvist, Fredri ...
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Bergström, Sven
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
- Articles in the publication
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mBio
- By the university
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Umeå University