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Published on: October 23, 2013
Chlamydia muridarum enters a viable but non-infectious state in amoxicillin-treated BALB/c mice
R Phillips Campbell1, J Kintner, J Whittimore
1Department of Biomedical Sciences, East Tennessee State University, Quillen College of Medicine, Johnson City, TN 37614, USA.
Abstract:
In culture, exposure to penicillin and other stressors induce chlamydiae to enter a non-infectious but viable state termed persistence. Chlamydiae may reenter their normal developmental cycle after stressor removal. Though aberrant RB similar to those present in culture models of persistence have been observed within infected tissues, the existence of persistent chlamydiae has not been definitively demonstrated in vivo. As a result, the role of persistent organisms in pathogenesis is undefined. In order to establish an experimentally tractable model of in vivo persistence, Chlamydia muridarum vaginally-infected mice were gavaged with either water or amoxicillin (amox). Vaginal swabs were collected for chlamydial titration and RNA isolated for quantification of pre-16s rRNA. Uterine tissue was analyzed by transmission electron microscopy (TEM). Although amox-treatment reduced vaginal shedding by >99%, C. muridarum pre-16s rRNA accumulation was unchanged by treatment. These data indicate that the amox-exposed organisms were viable but not infectious. Furthermore, TEM analyses demonstrated that inclusions in amox-treated animals contained primarily large, aberrant RB, but those observed in untreated control animals were normal. Collectively, these data suggest that amoxicillin treatment induces C. muridarum to enter the persistent state in vivo. This model also represents the first experimentally tractable animal model of chlamydial persistence.
Insights
Chlamydia muridarum exposed to amoxicillin in mice entered a viable but non-infectious persistent state. This study establishes a new animal model for studying chlamydial persistence in vivo.
Area of Science:
- Microbiology
- Infectious Diseases
- Pathogenesis
Background:
- Chlamydiae can enter a persistent state in vitro when exposed to stressors like penicillin.
- Persistent chlamydiae are viable but non-infectious, capable of resuming normal development upon stressor removal.
- The existence and role of persistent chlamydiae in vivo remain largely undefined.
Purpose of the Study:
- To establish an experimentally tractable in vivo model of chlamydial persistence.
- To investigate the effects of amoxicillin treatment on Chlamydia muridarum in a mouse model.
- To determine if chlamydial persistence can be induced in vivo.
Main Methods:
- Female mice were vaginally infected with Chlamydia muridarum.
- Mice were treated with amoxicillin (amox) or water.
- Vaginal shedding was quantified, and uterine tissue was analyzed by transmission electron microscopy (TEM).
- Chlamydial viability was assessed by pre-16s rRNA quantification.
Main Results:
- Amoxicillin treatment reduced vaginal shedding by over 99% but did not alter pre-16s rRNA levels, indicating viability.
- TEM revealed aberrant reticulate bodies (RB) in amoxicillin-treated mice, unlike the normal RB in controls.
- These findings suggest amoxicillin induced a persistent state in Chlamydia muridarum in vivo.
Conclusions:
- Amoxicillin treatment successfully induced a persistent state in Chlamydia muridarum in vivo.
- This study presents the first experimentally tractable animal model for chlamydial persistence.
- The developed model provides a platform for further research into the pathogenesis and treatment of chlamydial infections.
