PMID- 27532510
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20180507
IS  - 1462-5822 (Electronic)
IS  - 1462-5814 (Linking)
VI  - 19
IP  - 2
DP  - 2017 Feb
TI  - A pore-forming toxin enables Serratia a nonlytic egress from host cells.
LID - 10.1111/cmi.12656 [doi]
AB  - Several pathogens co-opt host intracellular compartments to survive and 
      replicate, and they thereafter disperse progeny to prosper in a new niche. Little 
      is known about strategies displayed by Serratia marcescens to defeat immune 
      responses and disseminate afterwards. Upon invasion of nonphagocytic cells, 
      Serratia multiplies within autophagosome-like vacuoles. These Serratia-containing 
      vacuoles (SeCV) circumvent progression into acidic/degradative compartments, 
      avoiding elimination. In this work, we show that ShlA pore-forming toxin (PFT) 
      commands Serratia escape from invaded cells. While ShlA-dependent, Ca(2)(+) local 
      increase was shown in SeCVs tight proximity, intracellular Ca(2)(+) sequestration 
      prevented Serratia exit. Accordingly, a Ca(2)(+) surge rescued a ShlA-deficient 
      strain exit capacity, demonstrating that Ca(2)(+) mobilization is essential for 
      egress. As opposed to wild-type-SeCV, the mutant strain-vacuole was wrapped by 
      actin filaments, showing that ShlA expression rearranges host actin. Moreover, 
      alteration of actin polymerization hindered wild-type Serratia escape, while 
      increased intracellular Ca(2)(+) reorganized the mutant strain-SeCV actin 
      distribution, restoring wild-type-SeCV phenotype. Our results demonstrate that, 
      by ShlA expression, Serratia triggers a Ca(2)(+) signal that reshapes 
      cytoskeleton dynamics and ends up pushing the SeCV load out of the cell, in an 
      exocytic-like process. These results disclose that PFTs can be engaged in 
      allowing bacteria to exit without compromising host cell integrity.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Di Venanzio, Gisela
AU  - Di Venanzio G
FAU - Lazzaro, Martina
AU  - Lazzaro M
FAU - Morales, Enrique S
AU  - Morales ES
AD  - Instituto de Biologia Molecular y Celular de Rosario, Consejo Nacional de 
      Investigaciones Cientificas y Tecnologicas, Universidad Nacional de Rosario, 
      Rosario, Argentina.
FAU - Krapf, Dario
AU  - Krapf D
AD  - Instituto de Biologia Molecular y Celular de Rosario, Consejo Nacional de 
      Investigaciones Cientificas y Tecnologicas, Universidad Nacional de Rosario, 
      Rosario, Argentina.
FAU - Garcia Vescovi, Eleonora
AU  - Garcia Vescovi E
AD  - Instituto de Biologia Molecular y Celular de Rosario, Consejo Nacional de 
      Investigaciones Cientificas y Tecnologicas, Universidad Nacional de Rosario, 
      Rosario, Argentina.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160923
PL  - India
TA  - Cell Microbiol
JT  - Cellular microbiology
JID - 100883691
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cations, Divalent)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (Pore Forming Cytotoxic Proteins)
RN  - 0 (ShlA protein, Serratia marcescens)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/*metabolism
MH  - CHO Cells
MH  - Calcium/metabolism
MH  - Calcium Signaling
MH  - Cations, Divalent/metabolism
MH  - Cricetinae
MH  - Cricetulus
MH  - Cytoskeleton/metabolism
MH  - *Exocytosis
MH  - Hemolysin Proteins/*metabolism
MH  - Pore Forming Cytotoxic Proteins/*metabolism
MH  - Serratia marcescens/metabolism/*physiology
MH  - Vacuoles/*microbiology
EDAT- 2016/08/18 06:00
MHDA- 2017/08/02 06:00
CRDT- 2016/08/18 06:00
PHST- 2016/05/12 00:00 [received]
PHST- 2016/07/28 00:00 [revised]
PHST- 2016/08/12 00:00 [accepted]
PHST- 2016/08/18 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2016/08/18 06:00 [entrez]
AID - 10.1111/cmi.12656 [doi]
PST - ppublish
SO  - Cell Microbiol. 2017 Feb;19(2). doi: 10.1111/cmi.12656. Epub 2016 Sep 23.