Chlamydia muridarum enters a viable but non-infectious state in amoxicillin-treated BALB/c mice

• Published in: Microbes and infection Vol. 14; no. 13; pp. 1177 - 1185
• Main Authors: Phillips Campbell, R., Kintner, J., Whittimore, J., Schoborg, R.V.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01-11-2012; Elsevier
• Subjects: Aberrant body; Aberrant reticulate body; Amoxicillin; Amoxicillin - pharmacology; Animal models; Animals; Anti-Bacterial Agents - pharmacology; Bacterial Shedding; Bacteriology; Biological and medical sciences; C. muridarum; C. trachomatis; Cell Line; Chlamydia; Chlamydia Infections - drug therapy; Chlamydia Infections - microbiology; Chlamydia muridarum - drug effects; Chlamydia muridarum - genetics; Chlamydia muridarum - growth & development; Chlamydia muridarum - ultrastructure; Chlamydial persistence; Data processing; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Humans; Mice; Mice, Inbred BALB C; Microbial Viability; Microbiology; Microscopy, Electron, Transmission; Miscellaneous; Penicillin; Retinoblastoma protein; RNA, Bacterial - isolation & purification; rRNA; Titration; Transmission electron microscopy; Uterus; Uterus - microbiology; Uterus - ultrastructure; Vagina; Vagina - microbiology; Chlamydial persistence; Aberrant reticulate body; C. muridarum; C. trachomatis; Aberrant body; Amoxicillin; Chlamydiaceae; β-Lactams; Rodentia; Penicillin derivatives; Vertebrata; Antibiotic; Mammalia; Chlamydia; Mouse; Chlamydiales; Bacteria; Antibacterial agent
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2012.07.017

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.