Transcriptional Response Patterns ofChlamydophila psittaciin Different In Vitro Models of Persistent Infection

Abstract

The obligatory intracellular bacterium Chlamydophila psittaci is the causative agent of psittacosis in birds and humans. The capability of this zoonotic pathogen to develop a persistent phase is likely to play a role in chronicity of infections, as well as in failure of antibiotic therapy and immunoprophylaxis. To elucidate three different in vitro models for transition of C. psittaci to persistence (iron depletion, penicillin G treatment, and gamma interferon [IFN-␥] exposure), a set of 27 genes was examined by mRNA expression analysis using quantitative real-time PCR. While the phenotypical characteristics were the same as in other chlamydiae, i.e., aberrant morphology of reticulate bodies, loss of cultivability, and rescue of infectivity upon removal of inducers, the transcriptional response of C. psittaci to persistence-inducing factors included several new and distinctive features. Consistent downregulation of membrane proteins, chlamydial sigma factors, cell division protein, and reticulate body-elementary body differentiation proteins from 24 h postinfection onward proved to be a general feature of C. psittaci persistence. However, other genes displayed considerable variations in response patterns from one model to another, which suggests that there is no persistence model per se. In contrast to results for Chlamydia trachomatis, late shutdown of essential genes in C. psittaci was more comprehensive with IFN-␥-induced persistence, which is probably due to the absence of a functional tryptophan synthesis operon.

A clinically silent respiratory infection withChlamydophilaspp. in calves is associated with airway obstruction and pulmonary inflammation

“…Even life-threatening situations have been reported in humans who became infected with zoonotic chlamydiae, such as C. psittaci originating from birds or C. abortus from small ruminants [9,12,28,54,55]. Secondly, chlamydial organisms are reported to persist and cause recurrent infections or re-activation of latent infections [7,11,25,46].…”

Chlamydia psittaci reference genes for normalisation of expression data differ depending on the culture conditions and selected time points during the chlamydial replication cycle

“…The expression of the 16S rRNA gene, extensively used as reference gene in Chlamydia spp. gene expression studies (1,7,8,10,14,15,20), and of nine other C. psittaci genes (map, tyrS, hemN, hflX, gidA, gatA, fumC, radA, and enoA) was studied during both normal bacterial growth conditions and penicillin-induced persistence.…”

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

“…Therefore, it is unknown whether any experimental chlamydial vaccine candidates could have a therapeutic effect, whether they might reduce or enhance pathological sequelae, or whether they could cause chronic, persistent infections, when administered during an infection. Knowing that Chlamydia can enter a persistent state when put under various pressures, including cytokine production, [92][93][94][95][96][97][98][99][100][101][102][103][104][105] it is plausible that enhancement of infection-induced immune responses by vaccination may cause the Chlamydia to enter this state and promote both pathology development and future reactivation of infection. It is also unknown whether any vaccine candidates administered after resolution of a previous genital infection will further boost the individual's infection-induced immune response, provide a greater level of protection and prevent further pathology development.…”