Import of bacterial pathogenicity factors into mitochondria

Kozjak-Pavlovic, Vera; Roß, Katharina; Rudel, Thomas

doi:10.1016/j.mib.2007.12.004

Cited by 45 publications

(43 citation statements)

References 39 publications

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“…We found that N. gonorrhoeae infection inhibits the release of cytochrome c from the mitochondrial intermembrane space, suggesting that N. gonorrhoeae inhibits apoptosis in PMNs by preventing mitochondrial depolarization. This effect may be mediated by the neisserial major outer membrane porin, which has been demonstrated to localize to mitochondria in infected cells and to mediate some of the pro-and antiapoptotic phenotypes effected by bacterial infection when cells are treated with purified protein (45,47,48,(50)(51)(52). The involvement of N. gonorrhoeae porin in modulating PMN survival during infection is under investigation.…”

Section: Discussionmentioning

confidence: 99%

Neisseria gonorrhoeae-Mediated Inhibition of Apoptotic Signalling in Polymorphonuclear Leukocytes

Chen

Seifert

2011

Infect Immun

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The human pathogen Neisseria gonorrhoeae recruits and interacts extensively with polymorphonuclear leukocytes (PMNs) during infection. N. gonorrhoeae is able to survive the bactericidal activity of these innate immune cells and can actively modulate PMN functions in vitro. PMNs are short-lived cells which readily undergo apoptosis, and thus the effect of N. gonorrhoeae infection on PMN survival has implications for whether PMNs might serve as an important site of bacterial replication during infection. We developed and validated an HL-60 myeloid leukemia cell culture model for PMN infection and used both these cells and primary PMNs to show that N. gonorrhoeae infection alone does not induce apoptosis and furthermore that N. gonorrhoeae can inhibit both spontaneous apoptosis and apoptosis induced by the intrinsic and extrinsic apoptosis inducers staurosporine (STS) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), respectively. N. gonorrhoeae infection also results in the activation of NF-B signaling in neutrophils and induces secretion of an identical profile of proinflammatory cytokines and chemokines in both HL-60 cells and primary PMNs. Our data show that the HL-60 cell line can be used to effectively model N. gonorrhoeae-PMN interactions and that N. gonorrhoeae actively inhibits apoptosis induced by multiple stimuli to prolong PMN survival and potentially facilitate bacterial survival, replication, and transmission.

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Section: Discussionmentioning

confidence: 99%

Neisseria gonorrhoeae-Mediated Inhibition of Apoptotic Signalling in Polymorphonuclear Leukocytes

Chen

Seifert

2011

Infect Immun

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“…In this study, we have investigated the localization of the M. tuberculosis PE_PGRS33 protein in transfected eukaryotic cells and have demonstrated that it co-localized to the mitochondria. Other bacterial proteins have also recently been found to associate with the mitochondria of host cells and in a few cases, a mitochondrial targeting sequence (MTS) with a putative cleavage signal is present at the N-terminal end of these proteins (Kozjak-Pavlovic et al, 2008;Nougayrède & Donnenberg, 2004;Papatheodorou et al, 2006). However, in other cases, bacterial proteins are targeted to the mitochondria without a discernible MTS, such as the Neisseria gonorrhoeae PorB protein which was shown to be imported into the host mitochondria by the same pathway used for the mitochondrial porin VDAC (Müller et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Induction of cell death after localization to the host cell mitochondria by the Mycobacterium tuberculosis PE_PGRS33 protein

et al. 2011

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PE_PGRS33 is the most studied member of the unique PE family of mycobacterial proteins. These proteins are composed of a PE domain (Pro–Glu motif), a linker region and a PGRS domain (polymorphic GC-rich-repetitive sequence). Previous studies have shown that PE_PGRS33 is surface-exposed, constitutively expressed during growth and infection, involved in creating antigenic diversity, and able to induce death in transfected or infected eukaryotic cells. In this study, we showed that PE_PGRS33 co-localizes to the mitochondria of transfected cells, a phenomenon dependent on the linker region and the PGRS domain, but not the PE domain. Using different genetic fusions and chimeras, we also demonstrated a direct correlation between localization to the host mitochondria and the induction of cell death. Finally, although all constructs localizing to the mitochondria did induce apoptosis, only the wild-type PE_PGRS33 with its own PE domain also induced primary necrosis, indicating a potentially important role for the PE domain. Considering the importance of primary necrosis in Mycobacterium tuberculosis dissemination during natural infection, the PE_PGRS33 protein may play a crucial role in the pathogenesis of tuberculosis.

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“…(60) Possible alteration of mitochondrial function by HLY is also consistent with that of the RTX toxin of Vibrio vulnificus, which has been shown to depolarize mitochondrial membranes, triggering cytochrome c release and apoptosis via a caspase-9-dependent pathway. (61) Several other bacterial pathogenicity factors have been shown to enter target cells and depolymerize actin filaments, (62) or bind mitochondria (63) . Examples include multifunctional autoprocessing repeats-in-toxin (MARTX) of Vibrio cholerae) and enteropathogenic E. coli mitochondrialassociated protein (Map) and EspF (reviewed in (63) ).…”

Section: Discussionmentioning

confidence: 99%

“…(61) Several other bacterial pathogenicity factors have been shown to enter target cells and depolymerize actin filaments, (62) or bind mitochondria (63) . Examples include multifunctional autoprocessing repeats-in-toxin (MARTX) of Vibrio cholerae) and enteropathogenic E. coli mitochondrialassociated protein (Map) and EspF (reviewed in (63) ).…”

Section: Discussionmentioning

confidence: 99%

Brief heat treatment causes a structural change and enhances cytotoxicity of theEscherichia coliα-hemolysin

Aulik

Atapattu

Czuprynski³

et al. 2012

Immunopharmacology and Immunotoxicology

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α-Hemolysin (HLY) is an important virulence factor for uropathogenic Escherichia coli. HLY is a member of the RTX family of exotoxins secreted by a number of Gram-negative bacteria. Recently, it was reported that a related RTX toxin, the Mannheimia haemolytica leukotoxin, exhibits increased cytotoxicity following brief heat treatment. In this article, we show that brief heat treatment (1 min at 100°C) increases cytotoxicity of HLY for human bladder cells, kidney epithelial cells (A498) and neutrophils. Heat treatment also increased hemolysis of human red blood cells (RBCs). Furthermore, heat treatment of previously inactived HLY restored its cytotoxicity. Heat-activated and native HLY both required glycophorin A to lyse RBCs. Native and heat-activated HLY appeared to bind equally well to the surface of A498 cells; although, Western blot analyses demonstrated binding to different proteins on the surface. Confocal microscopy revealed that heat-activated HLY bound more extensively to internal structures of permeabilized A498 cells than did native HLY. Several lines of spectroscopic evidence demonstrate irreversible changes in the structure of heat activated compared to native HLY. We show changes in secondary structure, increased exposure of tryptophan residues to the aqueous environment, an increase in molecular dimension and an increase in hydrophobic surface area. These properties are among the most common characteristics described for the molten globule state, first identified as an intermediate in protein folding. We hypothesize that brief heat treatment of HLY causes a conformational change leading to significant differences in protein-protein interactions that result in increased cytotoxicity for target cells.

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Import of bacterial pathogenicity factors into mitochondria

Cited by 45 publications

References 39 publications

Neisseria gonorrhoeae-Mediated Inhibition of Apoptotic Signalling in Polymorphonuclear Leukocytes

Neisseria gonorrhoeae-Mediated Inhibition of Apoptotic Signalling in Polymorphonuclear Leukocytes

Induction of cell death after localization to the host cell mitochondria by the Mycobacterium tuberculosis PE_PGRS33 protein

Brief heat treatment causes a structural change and enhances cytotoxicity of theEscherichia coliα-hemolysin

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