Members of the Pmp protein family of Chlamydia pneumoniae mediate adhesion to human cells via short repetitive peptide motifs.
Chlamydiae sp. are obligate intracellular pathogens that cause a variety of diseases in humans. Adhesion of the infectious elementary body to the eukaryotic host cell is a pivotal step in chlamydial pathogenesis. Here we describe the characterization of members of the polymorphic membrane protein family (Pmp), the largest protein family (with up to 21 members) unique to Chlamydiaceae. We show that yeast cells displaying Pmp6, Pmp20 or Pmp21 on their surfaces, or beads coated with the recombinant proteins, adhere to human epithelial cells. A hallmark of the Pmp protein family is the presence of multiple repeats of the tetrapeptide motifs FxxN and GGA(I, L, V) and deletion analysis shows that at least two copies of these motifs are needed for adhesion. Importantly, pre-treatment of human cells with recombinant Pmp6, Pmp20 or Pmp21 protein reduces infectivity upon subsequent challenge with Chlamydia pneumoniae and correlates with diminished attachment of Chlamydiae to target cells. Antibodies specific for Pmp21 can neutralize infection in vitro. Finally, a combination of two different Pmp proteins in infection blockage experiments shows additive effects, possibly suggesting similar functions. Our findings imply that Pmp6, Pmp20 and Pmp21 act as adhesins, are vital during infection and thus represent promising vaccine candidates.
Institut für Funktionelle Genomforschung der Mikroorganismen, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, Gebäude 25.02.U1, 40225 Düsseldorf, Germany.
Katja
K
Mölleken
Eleni
E
Schmidt
Johannes H
JH
Hegemann
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D001422:Bacterial Adhesion; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000472:pathogenicity*; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D020449:Repetitive Sequences, Amino Acid; D017384:Sequence Deletion
D018829:Adhesins, Bacterial