Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages

Hiemstra, Pieter S.; Barselaar, M. T. Van Den; Roest, Mark; Nibbering, Peter H.; Furth, R. van

doi:10.1002/jlb.66.3.423

Cited by 125 publications

(86 citation statements)

References 35 publications

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“…7b and data not shown). These results are consistent with the need for macrophage activation to detect the antimicrobial activity in the cytosol that was reported previously (Hiemstra et al, 1999), and suggest that Salmonella C. R. Beuzo! n, S. P. Salcedo It is interesting to consider the apparent contradiction between the different replication efficiencies of Salmonella and Listeria in the cytosol of macrophages, and their equal sensitivity in vitro to the antimicrobial activity activated by interferon-γ addition or by Salmonella infection.…”

Section: Evidence Of Salmonella Killing In the Cytosol Of Macrophagessupporting

confidence: 92%

“…To date only one cytosolic macrophage antimicrobial peptide, ubiquicidin, has been reported (Hiemstra et al, 1999). Ubiquicidin was purified from the cytosol of macrophages activated by the addition of interferon-γ, and displays antimicrobial activity in vitro against S. typhimurium as well as Y. enterocolitica, E. coli, Staphylococcus aureus and L. monocytogenes (Hiemstra (gentamicin-protected).…”

Section: Evidence Of Salmonella Killing In the Cytosol Of Macrophagesmentioning

confidence: 99%

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Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines

2002

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Intracellular pathogens have developed different mechanisms which enable their survival and replication within the host cells. Some survive and replicate within a membrane-bound vacuole modified by the bacteria to support microbial growth (e.g. Salmonella enterica serovar Typhimurium), whereas others escape from the vacuole into the host cell cytosol, where they proliferate (e.g. Listeria monocytogenes). In this study a Salmonella strain carrying a mutation in sifA which is released from the vacuole was used to analyse Salmonella survival and replication within the cytosol of several cell lines. It was found that Salmonella replicates within the cytosol of epithelial cells at a higher rate than that achieved when replicating within the vacuole, but is defective for replication in the cytosol of fibroblasts or macrophages. Using an aroC purD double mutant strain which does not replicate within host cells, it was shown that Salmonella encounters a killing activity within the cytosol of macrophages. Furthermore, in vitro experiments using cytosol extracted from either infected or uninfected macrophages suggested that this activity is activated upon Salmonella infection.

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Section: Evidence Of Salmonella Killing In the Cytosol Of Macrophagessupporting

confidence: 92%

Section: Evidence Of Salmonella Killing In the Cytosol Of Macrophagesmentioning

confidence: 99%

Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines

2002

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“…We suggest that the extensive cytosolic replication observed previously with LLOexpressing B. subtilis (7) and apathogenic L. innocua (28) might be also the result of such events. An alternative explanation could be that bacterial growth in the cytosol of intact host cells is restricted by antibacterial components, and this restriction is abolished in apoptotic (necrotic) cells (29).…”

Section: Discussionmentioning

confidence: 99%

Microinjection and growth of bacteria in the cytosol of mammalian host cells

Goetz

Bubert

Wang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

128

115

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Most facultative intracellular bacteria replicate in specialized phagosomes after being taken up by mammalian cells. Relatively few intracellular bacteria escape the phagosomal compartment with the help of cytolytic (pore-forming) proteins and replicate in the host cell cytosol. Without such toxins, intracellular bacteria cannot reach this cellular compartment. To circumvent the requirement of an ''escape'' step, we developed a procedure allowing the efficient direct injection of bacteria into the cytosol of mammalian cells. With this technique, we show that most bacteria, including extracellular bacteria and intracellular pathogens that normally reside in a vacuole, are unable to replicate in the cytosol of the mammalian cells. In contrast, microorganisms that replicate in the cytosol, such as Listeria monocytogenes, Shigella flexneri, and, to some extent, enteroinvasive Escherichia coli, are able to multiply in this cellular compartment after microinjection. Further L. monocytogenes with deletion in its PrfAregulated hpt gene was found to be impaired in replication when injected into the cytosol. Complementation of the hpt mutation with a plasmid carrying the wild-type hpt gene restored the replication ability in the cytosol. These data indicate that cytosolic intracellular pathogens have evolved specific mechanisms to grow in this compartment of mammalian cells. M any pathogenic bacteria are able to trigger their uptake by mammalian cells, which is followed by efficient multiplication of the internalized bacteria inside of the host cells. Internalization of these bacteria involves normal phagocytosis when the host cells are professional phagocytes, e.g., macrophages, or triggered phagocytosis in the case of nonprofessional phagocytic host cells, such as epithelial cells, hepatocytes, fibroblasts, and endothelial cells (1, 2). After internalization, most intracellular bacteria reside and replicate inside membrane-bound vacuoles that are specifically modified by the different bacteria (3, 4). Salmonella enterica, Legionella pneumophila, members of the Mycobacterium tuberculosis complex, Mycobacterium leprae, Brucella spp., Chlamydia, Rhodococcus equi, and several others belong to this group of intracellular bacteria. A smaller group of intracellular bacteria, including Shigella spp., the closely related enteroinvasive Escherichia coli (EIEC), Listeria monocytogenes, Listeria ivanovii, and Ricksettia spp., can escape from the primary phagosome into the host cell cytosol where the bacteria proficiently replicate. These latter bacteria synthesize specific proteins that disrupt the phagosomal membrane, thus allowing bacterial entry into the cytosol. In L. monocytogenes, the required proteins are best characterized and comprise the pore-forming lysteriolysin (LLO) and two phospholipases C, PlcA and PlcB (5, 6).It has been reported that the introduction and expression of the listerial hly gene (encoding LLO) in Bacillus subtilis leads to the release of these avirulent bacteria into the cytosol of mammalian cells wher...

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“…(Rossman et al, 2003). Other functions have been assigned to Fau as an immunosuppressor (Nakamura et al, 1995) and as an antimicrobial protein, ubiquicidin, isolated from the cytosolic fraction of an interferon-g-treated macrophage cell line (Hiemstra et al, 1999).…”

mentioning

confidence: 99%

Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression

et al. 2004

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Functional expression cloning is a powerful strategy for identifying critical steps in biological pathways independently of prior assumptions. It is particularly suitable for the identification of molecules crucial to the control of apoptosis. Our screen for sequences suppressing T-cell apoptosis isolated a sequence antisense to fau (FinkelBiskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene). The fox gene in FBR murine osteosarcoma virus is also antisense to fau and several reports have indicated that fau displays tumour suppressor and oncogenic properties in different contexts. Our observations indicate that the fau antisense sequence suppresses expression of endogenous fau mRNA and produces resistance to apoptosis induced both by the glucocorticoid analogue dexamethasone' by ultraviolet radiation, and by the anticancer drug cisplatin. In all cases, colony-forming ability is protected, indicating that fau affects the critical events prior to commitment to cell death. Overexpression of fau in the sense orientation induces cell death, which is inhibited both by Bcl-2 and by inhibition of caspases, in line with its proposed role in apoptosis.

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Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages

Cited by 125 publications

References 35 publications

Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines

Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines

Microinjection and growth of bacteria in the cytosol of mammalian host cells

Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression

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