title: Analysis of CPAF mutants: new functions, new questions (the ins and outs of a chlamydial protease).
abstract: The role of the chlamydial protease CPAF, previously described as a secreted serine protease processing a wealth of host and chlamydial proteins to promote chlamydial intracellular growth, has recently been questioned by studies from the groups of Tan and Sütterlin, who demonstrated that the reported proteolysis of almost a dozen substrates by CPAF occurred during preparation of cell lysates rather than in intact cells. Valdivia et al. have now compared near-isogenic pairs of CPAF-deficient and secretion-deficient mutants of Chlamydia trachomatis and their wild-type parent. Their report, published in this issue of Pathogens and Disease, is a landmark study in the emerging era of Chlamydia genetics. The results of Tan and Sütterlin are confirmed with a few additions. While CPAF's role in pathogenesis is diminished considerably from these studies, CPAF remains an important factor in chlamydial biology as (1) CPAF mutants produce less infectious yield than wild type; and (2) CPAF is responsible for proteolytic cleavage of vimentin and LAP-1, but only after lysis of the inclusion membrane, not upon CPAF secretion to the cytosol. Here, we briefly review the evidence in support of CPAF's active secretion from the mid-to-late inclusion and conclude that new experimentation to establish whether or not CPAF is actively secreted should precede any new investigation of CPAF's cellular activities during mid-to-late development.
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Patrik M
authors.initials: PM
authors.lastname: Bavoil
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Byrne
mesh_terms: D000818:Animals; D002692:Chlamydia trachomatis / Q000201:enzymology*; D054884:Host-Pathogen Interactions; D006801:Humans; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D010447:Peptide Hydrolases
keywords: Chlamydia; pathogenesis; protease