Benzylidene acylhydrazides inhibit chlamydial growth in a type III secretion- and Iron Chelation-Independent manner

Xiaofeng Bao, Åsa Gylfe, Gail L. Sturdevant L., Zheng Gong, Shuang Xu, Harlan D. Caldwell D., Mikael Elofsson, Huizhou Fan

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Chlamydiae are widespread Gram-negative pathogens of humans and animals. Salicylidene acylhydrazides, developed as inhibitors of type III secretion system (T3SS) in Yersinia spp., have an inhibitory effect on chlamydial infection. However, these inhibitors also have the capacity to chelate iron, and it is possible that their antichlamydial effects are caused by iron starvation. Therefore, we have explored the modification of salicylidene acylhydrazides with the goal to uncouple the antichlamydial effect from iron starvation. We discovered that benzylidene acylhydrazides, which cannot chelate iron, inhibit chlamydial growth. Biochemical and genetic analyses suggest that the derivative compounds inhibit chlamydiae through a T3SS-independent mechanism. Four single nucleotide polymorphisms were identified in a Chlamydia muridarum variant resistant to benzylidene acylhydrazides, but it may be necessary to segregate the mutations to differentiate their roles in the resistance phenotype. Benzylidene acylhydrazides are well tolerated by host cells and probiotic vaginal Lactobacillus species and are therefore of potential therapeutic value.

Original languageEnglish (US)
Pages (from-to)2989-3001
Number of pages13
JournalJournal of bacteriology
Volume196
Issue number16
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

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