Abstract
BackgroundChlamydia 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.ResultsSensitivity 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.ConclusionsThe 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.
Highlights
Chlamydia species are obligate intracellular bacteria that infect a broad range of mammalian hosts
LpxC from C. muridarum clusters most closely with C. suis and to the C. trachomatis serovars (Fig. 3a) and direct amino acid comparisons between the species did not reveal any obvious amino acid similarities shared between C. muridarum, C. abortus, and C. caviae, that were excluded from the other species (Fig. 3b), which suggest that the first hypothesis is more likely to be correct
We find that inhibition of LOS synthesis reverses the enhanced host-antigen presentation phenotype in all chlamydial species tested, and this does not appear to be the result of induced aberrancy as ampicillin treatment had no effect on antigen presentation but did induce aberrancy
Summary
Chlamydia species are obligate intracellular bacteria that infect a broad range of mammalian hosts. Members of the genus Chlamydia are obligate intracellular, intravacuolar, bacteria that can establish persistent infections in a variety of host species. All Chlamydia spp. undergo a biphasic developmental cycle inside host cells. After the inclusion reaches maturity, bacteria are released from the host cell by either lysis or extrusion continuing the cycle of infection [13]. While this process represents the typical, unobstructed chlamydial developmental cycle, encountering stress factors such as nutrient starvation, host interferon-γ (IFNγ), coinfection with herpesvirus, and exposure to antibiotics causes RBs to become
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