Salmonella enterica SpvB-mediated ADP-ribosylation as an activator for host cell actin degradation.
The virulence-associated SpvB protein of Salmonella enterica is a mono (ADP-ribosyl)transferase defined to target mammalian actin. Exposure of Acanthamoeba rhysodes cell lysate with SpvB and [32P]nicotinamide adenine dinucleotide (NAD) was here observed to result in labeling of a protein of 43 kDa that subsequently was identified as actin by immunoprecipitation. In parallel, ADP-ribosylation promoted degradation of the protozoan actin. SpvB-mediated actin degradation occurred in the presence of the serine protease inhibitor phenylmethylsulfonylfluoride (PMSF), but was inhibited upon addition of novobiocin, an inhibitor of mono (ADP-ribosyl)transferase activity, or upon addition of EDTA. Infection of A. rhysodes with SpvB-proficient S. enterica serovariant Dublin resulted in cytotoxicity and in characteristic SpvB-mediated actin degradation. Cells infected with SpvB-deficient bacteria showed a decrease in cytotoxicity and lack of actin degradation. Combining these results show that SpvB formally can ADP-ribosylate A. rhysodes actin but that the protozoan cell has the capacity to subsequently degrade ADP-ribosyl-tagged actin. These observations illustrate a hitherto undefined consequence of actin modification, and define a new pathway in the cellular actin dynamics.
Tezcan-Merdol
Dilek
D
Microbiology and Tumor Biology Centre, Karolinska Institute, Nobels väg 16, SE-17 177, Stockholm, Sweden.
Engstrand
Lars
L
Rhen
Mikael
M
D036002:ADP Ribose Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000656:Amoeba / Q000378:metabolism; D000818:Animals; D019779:Salmonella enterica / Q000201:enzymology / Q000378:metabolism* / Q000472:pathogenicity; D037521:Virulence Factors / Q000378:metabolism*
D000199:Actins; D037521:Virulence Factors; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; C415223:spvB protein, Salmonella enterica virulence plasmid