Expression of microbial virulence proteins in Saccharomyces cerevisiae models mammalian infection.
Bacterial virulence proteins that are translocated into eukaryotic cells were expressed in Saccharomyces cerevisiae to model human infection. The subcellular localization patterns of these proteins in yeast paralleled those previously observed during mammalian infection, including localization to the nucleus and plasma membrane. Localization of Salmonella SspA in yeast provided the first evidence that SspA interacts with actin in living cells. In many cases, expression of the bacterial virulence proteins conferred genetically exploitable growth phenotypes. In this way, Yersinia YopE toxicity was demonstrated to be linked to its Rho GTPase activating protein activity. YopE blocked polarization of the yeast cytoskeleton and cell cycle progression, while SspA altered polarity and inhibited depolymerization of the actin cytoskeleton. These activities are consistent with previously proposed or demonstrated effects on higher eukaryotes and provide new insights into the roles of these proteins in pathogenesis: SspA in directing formation of membrane ruffles and YopE in arresting cell division. Thus, study of bacterial virulence proteins in yeast is a powerful system to determine functions of these proteins, probe eukaryotic cellular processes and model mammalian infection.
Lesser
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Departments of Medicine and Microbiology, University of Washington, HSB K116, Box 357710, Seattle, WA 98195, USA.
Miller
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D000199:Actins / Q000187:drug effects; D018829:Adhesins, Bacterial / Q000633:toxicity; D001425:Bacterial Outer Membrane Proteins / Q000633:toxicity; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000633:toxicity*; D001431:Bacteriological Techniques; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D020690:GTPase-Activating Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D012475:Salmonella / Q000472:pathogenicity*; D014774:Virulence; D015008:Yersinia enterocolitica / Q000472:pathogenicity*
D000199:Actins; D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D020690:GTPase-Activating Proteins; D011994:Recombinant Proteins; C082314:SspA protein, bacteria; C085379:rho GTPase-activating protein; C063239:yopE protein, Yersinia