The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection

Attachment and uptake into host cells are pivotal steps in the life cycle of the <i>Chlamydiaceae</i>, a family of obligate intracellular pathogens. <i>Chlamydia trachomatis (Ctr)</i> possesses a family of nine polymorphic membrane proteins (Pmps), which have been shown to be crucial for adhesion and internalization. However, the host-cell molecules involved have so far remained unknown. Here, we show that a fragment of <i>Ctr</i> PmpD, which forms high-molecular-weight oligomers in solution and adheres to epithelial cells, also binds to secreted clusterin (sCLU), a chaperone-like protein that is secreted into the extracellular space by the host cell, and forms part of the chaperone- and receptor-mediated extracellular protein degradation (CRED) pathway. Using <i>in vitro</i> assays, we demonstrate that sCLU interacts directly with soluble rPmpD. In infection experiments, depletion of sCLU from the culture medium leads to a significant decrease in <i>Ctr</i> infection. Thus, sCLU is the first host-cell interaction partner identified for a <i>Ctr</i> Pmp and the first case in which sCLU has been shown to be a vital component for the establishment of a bacterial infection.