TitleChlamydia spp. development is differentially altered by treatment with the LpxC inhibitor LPC-011.
Publication TypeJournal Article
Year of Publication2017
AuthorsCram, ED, Rockey, DD, Dolan, BP
JournalBMC Microbiol
Date Published2017 04 24
KeywordsAmino Acid Sequence, Ampicillin, Animals, Anti-Bacterial Agents, Bacterial Proteins, Cell Line, Chlamydia, Chlamydia Infections, Cytoplasm, Fibroblasts, Gene Expression Regulation, Bacterial, Host-Pathogen Interactions, Humans, Hydroxamic Acids, Lipopolysaccharides, Mice, Microbial Sensitivity Tests, Phenotype, Phylogeny, Protein Biosynthesis, Sequence Alignment, Sequence Analysis, Protein, Sugar Acids, Threonine

BACKGROUND: Chlamydia species are obligate intracellular bacteria that infect a broad range of mammalian hosts. Members of related genera are pathogens of a variety of vertebrate and invertebrate species. Despite the diversity of Chlamydia, all species contain an outer membrane lipooligosaccharide (LOS) that is comprised of a genus-conserved, and genus-defining, trisaccharide 3-deoxy-D-manno-oct-2-ulosonic acid Kdo region. Recent studies with lipopolysaccharide inhibitors demonstrate that LOS is important for the C. trachomatis developmental cycle during RB- > EB differentiation. Here, we explore the effects of one of these inhibitors, LPC-011, on the developmental cycle of five chlamydial species.

RESULTS: Sensitivity to the drug varied in some of the species and was conserved between others. We observed that inhibition of LOS biosynthesis in some chlamydial species induced formation of aberrant reticulate bodies, while in other species, no change was observed to the reticulate body. However, loss of LOS production prevented completion of the chlamydial reproductive cycle in all species tested. In previous studies we found that C. trachomatis and C. caviae infection enhances MHC class I antigen presentation of a model self-peptide. We find that treatment with LPC-011 prevents enhanced host-peptide presentation induced by infection with all chlamydial-species tested.

CONCLUSIONS: The data demonstrate that LOS synthesis is necessary for production of infectious progeny and inhibition of LOS synthesis induces aberrancy in certain chlamydial species, which has important implications for the use of LOS synthesis inhibitors as potential antibiotics.

Alternate JournalBMC Microbiol
PubMed ID28438125
PubMed Central IDPMC5402638
Grant ListR01 AI094475 / AI / NIAID NIH HHS / United States
R21 AI088540 / AI / NIAID NIH HHS / United States
R21 AI121752 / AI / NIAID NIH HHS / United States