PMID- 27089365
OWN - NLM
STAT- MEDLINE
DCOM- 20161215
LR  - 20181113
IS  - 2072-6651 (Electronic)
IS  - 2072-6651 (Linking)
VI  - 8
IP  - 4
DP  - 2016 Apr 13
TI  - Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium 
      difficile Toxin B.
PG  - 109
LID - 10.3390/toxins8040109 [doi]
LID - 109
AB  - Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium 
      difficile (TcdB) belong to the family of the "Large clostridial glycosylating 
      toxins." These toxins mono-O-glucosylate low molecular weight GTPases of the Rho 
      and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually 
      involved in the toxic shock syndrome and the gas gangrene. TcdB-together with 
      Toxin A (TcdA)-is causative for the pseudomembranous colitis (PMC). Here, we 
      present evidence for the in vitro metal ion activation of the glucosyltransferase 
      and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is 
      found for activation by divalent metal ions: Mn(2+) > Co(2+) > Mg(2+) >> Ca(2+), 
      Cu(2+), Zn(2+). TcsL and TcdB thus require divalent metal ions providing an 
      octahedral coordination sphere. The EC50 values for TcsL were estimated at about 
      28 microM for Mn(2+) and 180 microM for Mg(2+). TcsL and TcdB further require 
      co-stimulation by monovalent K(+) (not by Na(+)). Finally, prebound divalent metal 
      ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the 
      conclusion that TcsL and TcdB recruit intracellular metal ions for activation of 
      the glucosyltransferase activity. With regard to the intracellular metal ion 
      concentrations, TcsL and TcdB are most likely activated by K(+) and Mg(2+) (rather 
      than Mn(2+)) in mammalian target cells.
FAU - Genth, Harald
AU  - Genth H
AD  - Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 
      Hannover, Germany. genth.harald@mh-hannover.de.
FAU - Schelle, Ilona
AU  - Schelle I
AD  - Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 
      Hannover, Germany. Ilona.Schelle@t-online.de.
FAU - Just, Ingo
AU  - Just I
AD  - Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 
      Hannover, Germany. just.ingo@mh-hannover.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160413
PL  - Switzerland
TA  - Toxins (Basel)
JT  - Toxins
JID - 101530765
RN  - 0 (Bacterial Proteins)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Metals)
RN  - 0 (lethal toxin LT, Clostridium sordellii)
RN  - 0 (toxB protein, Clostridium difficile)
RN  - 58-98-0 (Uridine Diphosphate)
RN  - EC 2.4.1.- (Glucosyltransferases)
RN  - EC 3.2.1.- (Glycoside Hydrolases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/*pharmacology
MH  - Bacterial Toxins/*pharmacology
MH  - Dogs
MH  - Glucose/metabolism
MH  - Glucosyltransferases/metabolism
MH  - Glycoside Hydrolases/metabolism
MH  - Hydrolysis
MH  - Madin Darby Canine Kidney Cells
MH  - Metals/*metabolism
MH  - Uridine Diphosphate/metabolism
PMC - PMC4848635
OTO - NOTNLM
OT  - Madin-Darby canine kidney (MDCK-C7) cells
OT  - Ras
OT  - Rho
OT  - UDP-glucose hydrolysis
OT  - cytopathic effect
OT  - glycosyltransferase
OT  - manganese
OT  - small GTPases
OT  - transepithelial resistance
EDAT- 2016/04/19 06:00
MHDA- 2016/12/16 06:00
PMCR- 2016/04/01
CRDT- 2016/04/19 06:00
PHST- 2016/03/21 00:00 [received]
PHST- 2016/04/05 00:00 [revised]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/04/19 06:00 [entrez]
PHST- 2016/04/19 06:00 [pubmed]
PHST- 2016/12/16 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - toxins8040109 [pii]
AID - toxins-08-00109 [pii]
AID - 10.3390/toxins8040109 [doi]
PST - epublish
SO  - Toxins (Basel). 2016 Apr 13;8(4):109. doi: 10.3390/toxins8040109.