Float like a butterfly

Among the Yersinia bacterial family, Y. pestis may be the best known owing to its plague-causing exploits during the Middle Ages. But now, its far less fearsome cousin, Y. enterocolitica, is making headlines of its own by spilling the secrets on many pathogenic bacteria thatcause disease and foil the immune system.

Y. enterocolitica causes food poisoning and enters humans through the mouth.Once inside, it passes through lymphatic tissue associated with the large and small intestines and eventually makes its way to the lymph nodes. Like other pathogenic Gram-negative bacteria, these bugs can secrete proteins through both their own membranes and those of eukaryotic cells. Although the primary structure of the secreted proteins and their machinery is known, protein translocation has been poorly understood.

SEAN KENNEDY

Egbert Hoiczyk and Günter Blobel of The Rockefeller University (New York) have shown that Y. enterocolitica polymerizes a 6-kDa protein from its secretion machinery, fashioning it into tiny needles that poke holes (see illustration at right) through the eukaryotic plasma membrane (Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 4669–4674).The needles act as channels through which proteins pass from the bacterium into the eukaryotic cytoplasm, where they carry out their toxic effects. The needles also kill or paralyze macrophages that are waiting on the other side of the intestinal tract to capture uninvited bacterial guests. Thus, Y. enterocolitica avoids certain destruction. “Once in contact with a cell, the needles are like a stinger on a bee,” Hoiczyk says.

Calcium depletion and the warmth of the host trigger needle production. Simultaneously, the bacterial cells become sticky, which enables them to attach to the host cell. Physical contact is thought to be the final trigger that tells the system it’s ready to go. By stunning the macrophages, they prevent themselves from being destroyed and can spread through the body on their way to the lymph nodes. “The needles telescope out through porelike channels in the bacterial outer membrane like a hand in a glove,” Hoiczyk says. The bacterium uses these pores to let the needles cross the bacterial membrane and deliver their poisonous load without disturbing it, he adds.

Other Gram-negative pathogens appear to share the same survival strategy. Needlelike structures have also been identified in Salmonella and Shigella, although the proteins responsible have not been identified. The discovery of the Yersinia needles, however, gives researchers a fighting chance against infection.