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Chlamydial persistence is a reversible state generated during conditions deleterious to growth. In persistence, Chlamydia trachomatis remains viable but atypical, with an enlarged, aberrant form and quiescent metabolism. It favours chronic chlamydiosis, leading to serious sequelae. Although the mechanism of persistence formation is still unknown, more reliable molecular approaches tend to confirm that its occurs in vivo, even lasting 3 years. One approach consists of identifying unprocessed rRNA found only in viable Chlamydia, when infection is not apparent. Another approach, referring to the fact that immunity is type-specific, consists of showing by genotyping that multiple recurrences are due to the same genovar. At the molecular level, persistence is characterized by increased expression of ct755, one of the three heat shock protein (hsp60)-coding genes. In addition, chromosomal replication occurs continuously, and cell division is blocked possibly due to the repression of genes such as ftsW and amiA. At the immunological level, persistence reveals the failure of host-defence mechanisms because of reduced or suppressed pro-inflammatory or cytotoxic responses.

Chlamydia trachomatis is a human pathogen that causes multiple diseases worldwide. Despite appropriate therapy with existing antichlamydial antibiotics, chronic exacerbated diseases often occur and lead to serious sequelae. Since C. trachomatis has been found to enter a persistent state after exposure to deleterious conditions, the role of persistence in the failure of chlamydial antibiotherapy is questioned. HeLa, THP-1 and U-937 cells were infected with 10(4)C. trachomatis serovar L2 infectious particles. Three days later the infected cells were treated with minimal bactericidal concentrations of doxycycline (DOX), erythromycin (ERY) or tetracycline (TET) for 24 days or 30 days. Antibiotic efficacy was assessed by measuring chlamydial inclusions and infectious particles, by investigating the resumption of chlamydial growth after antibiotic removal and by testing Chlamydia viability using reverse transcriptase polymerase chain reaction targeting unprocessed 16S rRNA, processed 16S rRNA and Omp-1 mRNA. Treatment of infected HeLa cells with the usual antichlamydial antibiotics suppressed chlamydial active growth. The infection remained unapparent. However, 24 days post treatment the bacterium was found to be viable, as proved by continued expression of unprocessed and processed 16S rRNA and Omp-1 mRNA. This inactive unapparent chlamydial state is not infectious, suggesting Chlamydia persistence. Chlamydia trachomatis also developed persistence both in permissive THP-1 and non-permissive U-937 cells. Unlike in HeLa cells, persistent chlamydial infection in THP-1 and U-937 cells was resolved after 30 days of DOX treatment. Of interest, we noticed that only THP-1 and U-937 cells that were persistently infected following their interaction with infected HeLa cells remained capable of transmitting active infection to HeLa cells. These findings suggest that DOX, TET and ERY, usually administered to combat chlamydial diseases, fail to resolve persistent infection occurring during treatment in non-immune HeLa cells. However, in immune THP-1 and U-937 cells, the persistent infection is resolved by therapy with DOX. Epithelial cells could be the reservoir of persistent chlamydial particles.