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Mutations in hemG Mediate Resistance to Salicylidene Acylhydrazides, Demonstrating a Novel Link between Protoporphyrinogen Oxidase (HemG) and Chlamydia trachomatis Infectivity
- Source :
- Journal of Bacteriology. 195:4221-4230
- Publication Year :
- 2013
- Publisher :
- American Society for Microbiology, 2013.
-
Abstract
- Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth and development of Chlamydia species. However, since the inhibition of Chlamydia growth by SAH is suppressed by the addition of excess iron and since SAHs have an iron-chelating capacity, their role as specific T3S inhibitors is unclear. We investigated here whether SAHs exhibit a function on C. trachomatis that goes beyond iron chelation. We found that the iron-saturated SAH INP0341 (IS-INP0341) specifically affects C. trachomatis infectivity with reduced generation of infectious elementary body (EB) progeny. Selection and isolation of spontaneous SAH-resistant mutant strains revealed that mutations in hemG suppressed the reduced infectivity caused by IS-INP0341 treatment. Structural modeling of C. trachomatis HemG predicts that the acquired mutations are located in the active site of the enzyme, suggesting that IS-INP0341 inhibits this domain of HemG and that protoporphyrinogen oxidase (HemG) and heme metabolism are important for C. trachomatis infectivity.
- Subjects :
- Models, Molecular
Iron
Molecular Sequence Data
Mutant
Chlamydia trachomatis
Heme
Yersinia
medicine.disease_cause
Microbiology
Type three secretion system
chemistry.chemical_compound
Bacterial Proteins
Catalytic Domain
Drug Resistance, Bacterial
medicine
Humans
Protoporphyrinogen Oxidase
cardiovascular diseases
Amino Acid Sequence
Molecular Biology
Infectivity
Mutation
biology
Articles
biology.organism_classification
Molecular biology
nervous system diseases
Hydrazines
chemistry
Protoporphyrinogen oxidase
HeLa Cells
Subjects
Details
- ISSN :
- 10985530 and 00219193
- Volume :
- 195
- Database :
- OpenAIRE
- Journal :
- Journal of Bacteriology
- Accession number :
- edsair.doi.dedup.....362e2415cf046c043c63fc8f49aad757