Chlamydiae include successful human pathogens that have an immense impact on public health. Chlamydia trachomatis is the most common sexually transmitted bacterial infection world-wide with an estimated 90 million new cases annually. In developing countries, C. trachomatis is the leading cause of preventable blindness. Additionally, growing evidence supports C. pneumoniae as a contributing factor of atherosclerosis and coronary disease, the second leading cause of human mortality. Despite its medical significance, many fundamental questions of chlamydial biology have yet to be elucidated, especially those related to developmental regulation and pathogenesis.
Chlamydiae are obligate intracellular bacteria that are perpetuated by a defining biphasic developmental cycle that is inexorably linked to pathogenesis. Intercellular transmission of Chlamydia occurs as a metabolically inert elementary body (EB) that, subsequent to gaining entry to the host cell, converts into a metabolically active, yet non-infectious, reticulate body (RB). Following numerous rounds of replication, reciprocal conversion occurs and the developmental cycle is repeated as EBs are released into the extracellular milieu. An important deviation from this cycle, especially clinically, is establishment of a persistent infection where RB to EB conversion is arrested. Relatively little information exists regarding specific extrinsic or intrinsic factors that regulate the developmental cycle and persistence. Moreover, the detailed events that occur during conversion processes are equally unknown.
Defining regulatory components of chlamydial development will provide critical insight to basic biology and mechanisms of pathogenesis. Our global transcriptional analysis of the developmental cycle revealed that virtually all genes differentially expressed are up-regulated during the developmental stage correlated with RB to EB conversion. This highlights the governing role of transcriptional regulation during this essential developmental stage. EBs exhibit extensive infectious capabilities as they bind, facilitate entry and establish a unique non-lysosomal vacuole requisite for chlamydial growth. Furthermore, induction of persistent infections results in RB to EB conversion arrest. Therefore, a research goal is to elucidate and characterize regulatory mechanisms of gene expression during chlamydial RB to EB conversion. Currently, research is focused on elucidating the role of an alternative sigma factor, s28, a transcriptional activator, ChxR, and the regulatory mechanisms for the type III secretion system during the developmental cycle.
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