Mannheimia haemolytica leukotoxin binds cyclophilin D on bovine neutrophil mitochondria

Aulik, Nicole; Hellenbrand, Katrina M.; Kisiela, Dagmara I.; Czuprynski, Charles J.

doi:10.1016/j.micpath.2011.01.001

Cited by 12 publications

(9 citation statements)

References 46 publications

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“…Moreover, cyclophilin-binding should favor prolines undergoing cis/trans isomerization 43 , such as P405 in HlyIIC. It has recently been reported that leukotoxin binds to cyclophilin D in neutrophil mitochondria thereby triggering the disruption of the mitochondrial membrane potential, release of cytochrome c, and apoptosis 44, 45 . The induction of apoptosis in neutrophils may help bacteria evade immune defenses.…”

Section: Discussionmentioning

confidence: 99%

NMR structure of the Bacillus cereus hemolysin II C-terminal domain reveals a novel fold

Kaplan

Kaus

et al. 2017

Sci Rep

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In addition to multiple virulence factors, Bacillus cereus a pathogen that causes food poisoning and life-threatening wound infections, secretes the pore-forming toxin hemolysin II (HlyII). The HlyII toxin has a unique 94 amino acid C-terminal domain (HlyIIC). HlyIIC exhibits splitting of NMR resonances due to cis/trans isomerization of a single proline near the C-terminus. To overcome heterogeneity, we solved the structure of P405M-HlyIIC, a mutant that exclusively stabilizes the trans state. The NMR structure of HlyIIC reveals a novel fold, consisting of two subdomains αA-β1-β2 and β3-β4-αB-β5, that come together in a barrel-like structure. The barrel core is fastened by three layers of hydrophobic residues. The barrel end opposite the HlyIIC-core has a positively charged surface, that by binding negatively charged moieties on cellular membranes, may play a role in target-cell surface recognition or stabilization of the heptameric pore complex. In the WT domain, dynamic flexibility occurs at the N-terminus and the first α-helix that connects the HlyIIC domain to the HlyII-core structure. In the destabilizing P405M mutant, increased flexibility is evident throughout the first subdomain, suggesting that the HlyIIC structure may have arisen through gene fusion.The soil-dwelling, spore-forming B. cereus bacterium 1-3 produces a number of virulence factors 4 including several secreted pore-forming toxins (PFTs) that form lytic channels in the membranes of target cells 5 . One of these toxins, hemolysin II (HlyII), is present in several closely related Bacillus species including B. cereus, B. thuringiensis (a bacterium that parasitizes insects and has insecticide applications), and B. anthracis (the cause of anthrax) 6, 7 . In B. cereus, expression of HlyII is under the control of the HlyIIR protein 8 , and the Fur system that regulates iron homeostasis 9,10 . Expression of HlyII is greater under oxic conditions than under conditions mimicking the intestinal tract, suggesting the toxin may not play a major role in gastrointestinal disease 11 . Although the physiological target of HlyII is not known, the purified toxin lyses rabbit and human erythrocytes 12 as well as other cultured mammalian cells 13,14 . In addition, the toxin can attack species like algae 15 and insects. Studies in mice and insects suggest that HlyII is involved in virulence, and that the toxin causes apoptosis of macrophages in vitro and in vivo 16 . HlyII belongs to a larger family of secreted toxins with similar predicted core structures including the B. cereus cytotoxin K (CytK) 17 , Staphylococcal hemolysins/leukocidins 18,19 , and toxins secreted by a variety of Vibrio species 20 . Similar to other family members, HlyII is secreted as a water-soluble monomer that assembles into a heptameric pore following binding to cell membranes 12,21 . A unique feature of HlyII is the attachment of a C-terminal domain consisting of 94 amino acids that shows no sequence or structural homology to other known proteins 18 . The C-terminal domain, henceforth r...

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Section: Discussionmentioning

confidence: 99%

NMR structure of the Bacillus cereus hemolysin II C-terminal domain reveals a novel fold

Kaplan

Kaus

et al. 2017

Sci Rep

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“…Most recently, monocytes/macrophages have also been reported to be capable of releasing ETs (Chow et al, 2010; Aulik et al, 2011). Macrophage ET production has been shown to be boosted by statins, which are inhibitors of the rate-limiting enzyme within the cholesterol biosynthesis 3-hydroxy 3-methyglutaryl coenzyme A (HMG-CoA) reductase.…”

Section: Extracellular Traps Formation Outside the Neutrophil Worldmentioning

confidence: 99%

“…The molecular mechanism mediating the effect of statins on phagocytes seems to be linked to the inhibition of the sterol pathway within the cell (Chow et al, 2010). Interestingly, bacterial components such as hemolysins of Escherichia coli or leukotoxin of Mannheimia haemolytica have been shown to induce the release of ETs by bovine macrophages (Aulik et al, 2011, 2012). However, the extent to which the molecular processes leading to the formation of ETs by monocytes/macrophages is comparable to the mechanisms already described for neutrophils, eosinophils, and mast cells, remains to be elucidated.…”

Section: Extracellular Traps Formation Outside the Neutrophil Worldmentioning

confidence: 99%

The expanding world of extracellular traps: not only neutrophils but much more

Goldmann¹,

Medina²

2013

Front. Immun.

163

169

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The release of extracellular traps (ETs) is a recently described mechanism of innate immune response to infection. Although ETs have been intensely investigated in the context of neutrophil antimicrobial effector mechanisms, other immune cells such as mast cells, eosinophils, and macrophages can also release these structures. The different ETs have several features in common, regardless of the type of cells from which they originated, including a DNA backbone with embedded antimicrobial peptides, proteases, and histones. However, they also exhibit remarkable individual differences such as the type of sub-cellular compartments from where the DNA backbone originates (e.g., nucleus or mitochondria), the proportion of responding cells within the pool, and/or the molecular mechanism/s underlying the ETs formation. This review summarizes the knowledge accumulated in recent years regarding the complex and expanding world of ETs and their role in immune function with particular emphasis on the role of other immune cells rather than on neutrophils exclusively.

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“…Further studies showed that LktA is able to enter into and traffic to the mitochondria of BL-3 cells, where it interacts with the translocase of the outer membrane of mitochondria (TOM) and cyclophilin D, a member of the mitochondria permeability transition pore [384,385].…”

Section: Interaction With Cell Receptors and Trafficmentioning

confidence: 99%