In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 4 ( 2022-4-7), p. e1010434-
Abstract:
Enterococcus faecalis is a frequent opportunistic pathogen of wounds, whose infections are associated with biofilm formation, persistence, and recalcitrance toward treatment. We have previously shown that E . faecalis wound infection persists for at least 7 days. Here we report that viable E . faecalis are present within both immune and non-immune cells at the wound site up to 5 days after infection, raising the prospect that intracellular persistence contributes to chronic E . faecalis infection. Using in vitro keratinocyte and macrophage infection models, we show that E . faecalis becomes internalized and a subpopulation of bacteria can survive and replicate intracellularly. E . faecalis are internalized into keratinocytes primarily via macropinocytosis into single membrane-bound compartments and can persist in late endosomes up to 24 h after infection in the absence of colocalization with the lysosomal protease Cathepsin D or apparent fusion with the lysosome, suggesting that E . faecalis blocks endosomal maturation. Indeed, intracellular E . faecalis infection results in heterotypic intracellular trafficking with partial or absent labelling of E . faecalis -containing compartments with Rab5 and Rab7, small GTPases required for the endosome-lysosome trafficking. In addition, E . faecalis infection results in marked reduction of Rab5 and Rab7 protein levels which may also contribute to attenuated Rab incorporation into E . faecalis- containing compartments. Finally, we demonstrate that intracellular E . faecalis derived from infected keratinocytes are significantly more efficient in reinfecting new keratinocytes. Together, these data suggest that intracellular proliferation of E . faecalis may contribute to its persistence in the face of a robust immune response, providing a primed reservoir of bacteria for subsequent reinfection.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010434
DOI:
10.1371/journal.ppat.1010434.g001
DOI:
10.1371/journal.ppat.1010434.g002
DOI:
10.1371/journal.ppat.1010434.g003
DOI:
10.1371/journal.ppat.1010434.g004
DOI:
10.1371/journal.ppat.1010434.g005
DOI:
10.1371/journal.ppat.1010434.g006
DOI:
10.1371/journal.ppat.1010434.g007
DOI:
10.1371/journal.ppat.1010434.g008
DOI:
10.1371/journal.ppat.1010434.g009
DOI:
10.1371/journal.ppat.1010434.s001
DOI:
10.1371/journal.ppat.1010434.s002
DOI:
10.1371/journal.ppat.1010434.s003
DOI:
10.1371/journal.ppat.1010434.s004
DOI:
10.1371/journal.ppat.1010434.s005
DOI:
10.1371/journal.ppat.1010434.s006
DOI:
10.1371/journal.ppat.1010434.s007
DOI:
10.1371/journal.ppat.1010434.s008
DOI:
10.1371/journal.ppat.1010434.s009
DOI:
10.1371/journal.ppat.1010434.s010
DOI:
10.1371/journal.ppat.1010434.s011
DOI:
10.1371/journal.ppat.1010434.s012
DOI:
10.1371/journal.ppat.1010434.s013
DOI:
10.1371/journal.ppat.1010434.s014
DOI:
10.1371/journal.ppat.1010434.s015
DOI:
10.1371/journal.ppat.1010434.s016
DOI:
10.1371/journal.ppat.1010434.s017
DOI:
10.1371/journal.ppat.1010434.s018
DOI:
10.1371/journal.ppat.1010434.r001
DOI:
10.1371/journal.ppat.1010434.r002
DOI:
10.1371/journal.ppat.1010434.r003
DOI:
10.1371/journal.ppat.1010434.r004
DOI:
10.1371/journal.ppat.1010434.r005
DOI:
10.1371/journal.ppat.1010434.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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