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The spectrin cytoskeleton is crucial for adherent and invasive bacterial pathogenesis.

TitleThe spectrin cytoskeleton is crucial for adherent and invasive bacterial pathogenesis.
Publication TypeJournal Article
Year of Publication2011
AuthorsRuetz T, Cornick S, Guttman JAndrew
JournalPLoS One
Volume6
Issue5
Paginatione19940
Date Published2011
ISSN1932-6203
KeywordsBacterial Adhesion, Cytoskeletal Proteins, Enterobacteriaceae, Enterobacteriaceae Infections, Escherichia coli, HeLa Cells, Host-Pathogen Interactions, Humans, Listeria monocytogenes, Salmonella typhimurium, Spectrin
Abstract

Various enteric bacterial pathogens target the host cell cytoskeletal machinery as a crucial event in their pathogenesis. Despite thorough studies detailing strategies microbes use to exploit these components of the host cell, the role of the spectrin-based cytoskeleton has been largely overlooked. Here we show that the spectrin cytoskeleton is a host system that is hijacked by adherent (Entropathogenic Escherichia coli [EPEC]), invasive triggering (Salmonella enterica serovar Typhimurium [S. Typhimurium]) and invasive zippering (Listeria monocytogenes) bacteria. We demonstrate that spectrin cytoskeletal proteins are recruited to EPEC pedestals, S. Typhimurium membrane ruffles and Salmonella containing vacuoles (SCVs), as well as sites of invasion and comet tail initiation by L. monocytogenes. Spectrin was often seen co-localizing with actin filaments at the cell periphery, however a disconnect between the actin and spectrin cytoskeletons was also observed. During infections with S. Typhimurium ΔsipA, actin-rich membrane ruffles at characteristic sites of bacterial invasion often occurred in the absence of spectrin cytoskeletal proteins. Additionally, early in the formation of L. monocytogenes comet tails, spectrin cytoskeletal elements were recruited to the surface of the internalized bacteria independent of actin filaments. Further studies revealed the presence of the spectrin cytoskeleton during SCV and Listeria comet tail formation, highlighting novel cytoplasmic roles for the spectrin cytoskeleton. SiRNA targeted against spectrin and the spectrin-associated proteins severely diminished EPEC pedestal formation as well as S. Typhimurium and L. monocytogenes invasion. Ultimately, these findings identify the spectrin cytoskeleton as a ubiquitous target of enteric bacterial pathogens and indicate that this cytoskeletal system is critical for these infections to progress.

DOI10.1371/journal.pone.0019940
Alternate JournalPLoS ONE
PubMed ID21603579
PubMed Central IDPMC3095645
Grant List / / Canadian Institutes of Health Research / Canada
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