title: Virulent Burkholderia species mimic host actin polymerases to drive actin-based motility.
abstract: Burkholderia pseudomallei and B. mallei are bacterial pathogens that cause melioidosis and glanders, whereas their close relative B. thailandensis is non-pathogenic. All use the trimeric autotransporter BimA to facilitate actin-based motility, host cell fusion, and dissemination. Here, we show that BimA orthologs mimic different host actin-polymerizing proteins. B. thailandensis BimA activates the host Arp2/3 complex. In contrast, B. pseudomallei and B. mallei BimA mimic host Ena/VASP actin polymerases in their ability to nucleate, elongate, and bundle filaments by associating with barbed ends, as well as in their use of WH2 motifs and oligomerization for activity. Mechanistic differences among BimA orthologs resulted in distinct actin filament organization and motility parameters, which affected the efficiency of cell fusion during infection. Our results identify bacterial Ena/VASP mimics and reveal that pathogens imitate the full spectrum of host actin-polymerizing pathways, suggesting that mimicry of different polymerization mechanisms influences key parameters of infection.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Electronic address: ebenanti@aduro.com.
authors: Erin L
authors: EL
authors: Benanti
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors: Catherine M
authors: CM
authors: Nguyen
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Electronic address: welch@berkeley.edu.
authors: Matthew D
authors: MD
authors: Welch
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019117:Burkholderia / Q000145:classification / Q000201:enzymology / Q000472:pathogenicity* / Q000502:physiology*; D019121:Burkholderia Infections / Q000382:microbiology*; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D016415:Sequence Alignment; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein