Tackling the intractable - approaching the genetics of Chlamydiales.

ABSTRACT

Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae are important human pathogens with significant socio-economic and medical impact. The development of an improved therapy or vaccine would represent a major break-through in the battle against these infections. Despite intense research on Chlamydiaceae, the molecular genetic analysis of these pathogens remains difficult as genetic manipulation still remains impossible. Even though several options for generating a universal genetic system are currently being pursued, the anticipated success of these approaches is uncertain. As an alternative approach, random chemical mutagenesis is currently pursued which could allow spotlighting critical chlamydial pathogenesis features in the near future. Another research track lies in the identification of immunogenic peptides which could serve two goals Immunogenic peptides could provide a basis for generating an efficient antichlamydial vaccine. Further, they also might offer an efficient tool to diagnose acute and chronic chlamydial infections. Both are currently pursued by applying the autodisplay approach that facilitates the exposure of whole peptide libraries on the Escherichia coli cell surface, thus allowing immediate detection and gene tracking through antibody binding. Finally, global transcriptome analysis is an approach to circumvent the genetic intractability of Chlamydiaceae. Current analysis indicates that gene expression takes place in an ordered manner throughout the course of the developmental cycle and, as expected, gene expression appears to be directly linked to host cell responses. Moreover, recent microarray analysis in C. pneumoniae corroborated the notion that distinct mRNA species are being carried-over by the infectious elementary bodies (EBs). These and other recent observations on the chlamydial gene expression patterns offer unique opportunities to interfere with the onset, the course, and the persistency of chlamydial infections by paving the ways towards the development of novel diagnostic and therapeutic treatment regimens.