**6. Molecular basis of Chlamydial persistence**

During the persistent state, *Chlamydiae* can activate pro-survival pathways and inhibit apoptosis to ensure long-term survival inside the cells. Extensive research has established a strong correlation between inhibition of host cell apoptosis and persistent *C. trachomatis* infection.

#### **6.1 Inhibition of apoptosis**

Apoptosis is an active process of cellular death induced by both extrinsic (death receptor signaling) and intrinsic (mitochondrial) pathways in response to variety of physiological and stress stimuli. Host cell death has long been recognized as the final stage of the *Chlamydia* infection cycle, enabling the release of EBs and spreads of infection. However, *Chlamydia* must protect the host cell from succumbing to stress-induced death before the Chlamydial developmental cycle is complete. The ability of *Chlamydiae* to induce host-cell apoptosis under some circumstances and actively inhibit apoptosis to complete their obligate intracellular growth has been extensively studied for decades ([78]; reviewed in Ref. [79]). *C. trachomatis* inhibits specifically the mitochondrial pathway, while signals that originate at death receptors and bypass mitochondria are not blocked [80]. Apoptosis inhibition in *Chlamydia* is observed in a variety of cell lines and primary cells from diverse origins, including epithelial cells, fibroblasts, endothelial cells, monocytes, and lymphoid cells, and not only during active but also during persistent infection [78].

#### *6.1.1 Interaction with mitochondria*

Mitochondria play a central role in energy (ATP) metabolism via oxidative phosphorylation, biosynthesis of macromolecules, and cell death regulation. Within the

#### *Persistence in* Chlamydia *DOI: http://dx.doi.org/10.5772/intechopen.109299*

host cell, the mitochondria constitute the primary target for *C. trachomatis*. Its high demand for metabolites during its inclusion phase induces massive stress in the host cell, eventually leading to the induction of apoptotic cell death as a cell autonomous defense mechanism. Accumulating evidence suggests that *Chlamydia* can manipulate the mitochondrial morphology to promote their own replication or to escape from host immune responses (Reviewed in Ref. [81]). Altered mitochondrial dynamics of fusion and fission allow *Chlamydia* to maintain the cycle of reproduction and growth*. Chlamydia* suppresses mitochondrial fission and promotes mitochondrial fusion in the host cell via lowering ROS generation, inhibiting the tumor suppressor protein P53 transcription, increasing P53 protein ubiquitination levels, and inhibiting the dynamin-related protein 1(DRP1) oligomerization [81, 82]. Another study provided evidence that *Chlamydia* promotes intracellular survival by inducing mitochondrial elongation during the early phase of infection via phosphorylated fission mediator protein Drp1 followed by a fragmentation phase at the late stages of infection [83].
