A Secreted Ankyrin-Repeat Protein from Clinical Stenotrophomonas maltophilia Isolates Disrupts Actin Cytoskeletal Structure.
Stenotrophomonas maltophilia is an emerging, multidrug-resistant pathogen of increasing importance for the immunocompromised, including cystic fibrosis patients. Despite its significance as an emerging pathogen, relatively little is known regarding the specific factors and mechanisms that contribute to its pathogenicity. We identify and characterize a putative ankyrin-repeat protein (Smlt3054) unique to clinical S. maltophilia isolates that binds F-actin in vitro and co-localizes with actin in transfected HEK293a cells. Smlt3054 is endogenously expressed and secreted from clinical S. maltophilia isolates, but not an environmental isolate (R551-3). The in vitro binding of Smlt3054 to F-actin resulted in a thickening of the filaments as observed by TEM. Ectopic expression of Smlt3054-GFP exhibits strong co-localization with F-actin, with distinct, retrograde F-actin waves specifically associated with Smlt3054 in individual cells as well as formation of dense, internal inclusions at the expense of retrograde F-actin waves. Collectively, our results point to an interaction between Smlt3054 and F-actin. Furthermore, as a potentially secreted protein unique to clinical S. maltophilia isolates, Smlt3054 may serve as a starting point for understanding the mechanisms by which S. maltophilia has become an emergent pathogen.
Program in Bioengineering and Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Logan C
LC
MacDonald
Program in Bioengineering and Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Sean
S
O'Keefe
Program in Bioengineering and Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Mei-Fan
MF
Parnes
Program in Bioengineering and Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Hanlon
H
MacDonald
Program in Bioengineering and Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Lindsey
L
Stretz
Division of Infectious Disease, Lehigh Valley Health Network , 1250 South Cedar Crest Boulevard, Suite 200, Allentown, Pennsylvania 18103, United States.
Suzanne J
SJ
Templer
Division of Infectious Disease, Lehigh Valley Health Network , 1250 South Cedar Crest Boulevard, Suite 200, Allentown, Pennsylvania 18103, United States.
Emily L
EL
Wong
Program in Bioengineering and Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Bryan W
BW
Berger
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000382:microbiology; D000199:Actins / Q000378:metabolism; D017089:Ankyrin Repeat; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism* / Q000502:physiology*; D003428:Cross Infection / Q000382:microbiology; D003550:Cystic Fibrosis / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D015398:Signal Transduction; D020615:Stenotrophomonas maltophilia / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity*
D000199:Actins; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins
Stenotrophomonas maltophilia; actin-binding protein; ankyrin-repeat protein