Metabolic dormancy in Chlamydia trachomatis treated with different antibiotics

Diseases caused by spp. are often associated with persistent infections. Chlamydial persistence is commonly associated with a unique non-infectious intracellular developmental form, termed an aberrant form. Although infectious chlamydiae can be cultured consistently in cells stressed to aberrancy, t...

Full description

Saved in:
Bibliographic Details
Published in:Infection and immunity 2024-02, Vol.92 (2), p.e0033923
Main Authors: Rockey, Daniel D, Wang, Xisheng, Debrine, Abigail, Grieshaber, Nicole, Grieshaber, Scott S
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Bacterial Infections
Bacteriology
Chlamydia Infections - drug therapy
Chlamydia Infections - microbiology
Chlamydia trachomatis
Humans
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Diseases caused by spp. are often associated with persistent infections. Chlamydial persistence is commonly associated with a unique non-infectious intracellular developmental form, termed an aberrant form. Although infectious chlamydiae can be cultured consistently in cells stressed to aberrancy, their role in persistence is not clear. Recovery from antibiotic stress was explored as a model to determine how survival of non-aberrant chlamydiae, in the presence of fully inhibitory drug concentrations, may participate in persistence. Assays included incubation in quinolones, tetracyclines, or chloramphenicol for differing lengths of time, followed by an extended recovery period in antibiotic-free media. Culturable elementary bodies were not detected during treatment with each antibiotic, but viable and culturable emerged after the drug was removed. Time-lapse imaging of live, antibiotic-treated infected cells identified metabolically dormant developmental forms within cells that emerged to form typical productive inclusions. The effects of the increasing concentration of most tested antibiotics led to predictable inhibitory activity, in which the survival rate decreased with increasing drug concentration. In contrast, in fluoroquinolone-treated cells, there was a paradoxical increase in productive development that was directly correlated with drug concentration and inversely associated with aberrant form production. This model system uncovers a unique chlamydial persistence pathway that does not involve the chlamydial aberrant form. The association between productive latency and metabolic dormancy is consistent with models for many bacterial species and may lead to a different interpretation of mechanisms of chlamydial persistence in patients.IMPORTANCEThe life history of most pathogens within the genus a relies on lengthy persistence in the host. The most generally accepted model for spp. persistence involves an unusual developmental stage, termed the aberrant form, which arises during conditions that mimic a stressful host environment. In this work, we provide an alternate model for chlamydial persistence in the face of antibiotic stress. This model may be relevant to antibiotic treatment failures in patients infected with .
ISSN:0019-9567
1098-5522
1098-5522
DOI:10.1128/iai.00339-23