**9. Concluding remarks**

*Chlamydia's* ability to manipulate the host cell biology, evade immunity, and undergo morphological aberrant conformations allows these successful intracellular pathogens to enter a persistent state. Persistence has been studied for decades by observing the ability of *Chlamydia* to survive for long periods of time in cell culture in response to stress stimuli. The stress responses that lead to persistence in *Chlamydia* comprise complex regulatory networks that control the expression of multiple genes to inhibit apoptosis and activate pro-signaling pathways and immunomodulation. The transcriptional response of *Chlamydia* differs according to the persistence-inducing

stimuli, suggesting differences in the host cell response. On the other hand, isolated *in vitro* studies indicate common pathways that are down- or upregulated in a similar way by different stress conditions, which may interact and crosstalk between these regulons. Thus, an understanding of the morphological features, as well as the regulatory mechanisms and functional redundancies in pathways involved in persistence, is very critical for the design of novel anti-Chlamydial strategies.

Methodological advances in *Chlamydial* gene mutagenesis and DNA transformation, deep sequencing technologies, and the implementation of high-throughput genome-scale analysis and improvement in *in vitro* cell systems have opened new opportunities in our understanding of persistence. The genes encoding critical functional proteins are potential drug targets for treating persistent *C. trachomatis* infections. Understanding the gene-level changes that take place for *Chlamydia* to enter persistence could help researchers develop strategies to block these changes from occurring, making the organism more vulnerable to antibiotics and circumventing chronic Chlamydial infections.
