1.C.3 The α-Hemolysin Channel-forming Toxin (αHL) Family

The α-hemolysin (αHL; α-toxin, alpha-toxin) of the human pathogen Staphylococcus aureus is secreted as a 33 kDa monomer. This monomeric species associates with animal cell membranes to form a 232 kDa homoheptameric transmembrane β-barrel pore that promotes cell death by allowing bilayer permeability to ions, water and small solutes, thereby promoting cell lysis. The three-dimensional structure of αHL has been solved by x-ray crystallography to 1.9 Å resolution (Song et al., 1996). Imaging αHL with molecular dynamics has provided information about its ionic conductance and osmotic permeability (Aksimentiev and Schulten 2005). αHL forms a solvent-filled channel with a length of 100 Å, that runs along the seven-fold axis of the protein and ranges from 14 to 46 Å in diameter. The transmembrane domain of the mushroom-shaped heptamer is the lower portion of the mushroom, consisting of a 14-strand antiparallel β-barrel to which each protomer contributes two α-strands, each 65 Å long. The interior of the β-barrel is primarily hydrophilic, and the exterior has a hydrophobic belt 28 Å wide. The pore can transport peptides, and charged residues in the pore influences the rate of passage (Wolfe et al., 2007Hammerstein et al., 2011). αHL has been used to create a system with directional control of a processive molecular hopper (Qing et al. 2018).  Sphingomyelin depletion from the plasma membranes of human airway epithelial cells completely abrogates the deleterious actions of alpha-toxin (Ziesemer et al. 2019).

Several Staphylococcal toxins of this family are two-component cytolysins. These toxins include α-hemolysin (Hlg: Hlg1 (LukF) Hlg2), leukocidin (Luk: LukF LukS) and Pantone-Valentine leukocidin (Luk-PV: LukF-PV LukS-PV). They have 7 subunits arranged in a ring with alternate subunit arrangements (subunit stoichiometries of 3:4 or 4:3 (Sugawara-Tomita et al., 2002). Each toxin has specificity for different mammalian cell types and hosts. LukF (also called Hlg1) and LukF-PV comprise class F while Hlg2, LukS and LukS-PV comprise class S. Proteins of each class are 70% identical, but the proteins are about 30% identical between classes. They are 20-30% identical to the single component Staphylococcal α-hemolysin described above. Because the two components (LukS and LukF) comprise two distinct subfamilies of the αHL family, they are listed under two different TC numbers (#1.C.3.3.1 and #1.C.3.4.1).

The αHL family consists of pore-forming toxins from Staphylococcal species, Bacillus cereus, B. anthracis and Clostridium perfringens. They are distantly related to the CHL family of pentameric toxins from Gram-negative bacteria (TC #1.C.14). The S. aureus protein monomers are 308-326 residues in length, while the B. cereus protein is of 412 residues and the C. perfringens monomers is of 336 residues. α-HL forms two subpopulations of ion conducting channels. Furini et al. (2008) provided evidence that this toxin can form both hexameric and heptameric pores, accounting for the ion conuctance results.

The phylogenetic tree for the αHL family reveals four clusters (Saier et al., 1999). The Staphylococcus α-hemolysin for which the three-dimensional structure is available comprises one branch, the B. cereus and C. perfringens proteins comprise a second, and all other members of the family fall into the remaining two clusters.

α-haemotoxins are members of the αHL family that form heterooligomeric (bicomponent) toxins (HlgA · HlgB or HlgB · HlgC). Both form pores in lipid membranes with conductances, current-voltage characeristics and stability properties similar to α-toxin. However, they are cation selective rather than anion selective. There is a conserved region at the pore entrance with four basic residues in α-toxin but either basic or acidic residues in α-haemolysins. These residues form an entrance electrostatic filter (Comai et al. 2002).  A variety of peptides interact with αHL (Movileanu et al. 2005).

Cracknell et al. (2013) described the translocation of ssRNA heteropolymers (91-6083 bases) through the α-hemolysin nanopore. Translocation of these long ssRNAs is characterized by surprisingly long, almost complete ionic current blockades with durations averaging milliseconds per base (at +180 mV). The event durations decrease exponentially with increased transmembrane potential but are largely unaffected by the presence of urea. When the ssRNA is coupled at the 3' end to streptavidin, which cannot translocate through the pore, permanent blockades are observed, supporting the conclusion that the transient blockage of current arises from ssRNA translocation.  Asandei et al. 2016 have described the dynamics of a single peptide as it passes across a voltage-biased alpha-hemolysin nanopore.

PLEKHA7 and other junctional proteins are host factors mediating death by S. aureus alpha-toxin. ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C-terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. ADAM10 is locked at junctions through binding of its cytoplasmic C terminus to afadin. Junctionally clustered ADAM10 supports the efficient formation of stable toxin pores. Disruption of the PLEKHA7-PDZD11 complex inhibits ADAM10 and toxin junctional clustering. This promotes toxin pore removal from the cell surface through an actin- and macropinocytosis-dependent process, resulting in cell recovery from initial injury and survival. Thus, a dock-and-lock molecular mechanism targets ADAM10 to junctions, providing a paradigm for how junctions may regulate transmembrane receptors through their clustering (Shah et al. 2018).

The generalized transport reaction catalyzed by these pore-forming toxins is:

Small molecules (in) Small molecules (out)



This family belongs to the Aerolysin Superfamily.

 

References:

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Aksimentiev, A. and K. Schulten. (2005). Imaging α-hemolysin with molecular dynamics: ionic conductance, osmotic permeability, and the electrostatic potential map. Biophys. J. 88: 3745-3761.

Asandei, A., I. Schiopu, M. Chinappi, C.H. Seo, Y. Park, and T. Luchian. (2016). Electroosmotic Trap Against the Electrophoretic Force Near a Protein Nanopore Reveals Peptide Dynamics During Capture and Translocation. ACS Appl Mater Interfaces 8: 13166-13179.

Baaske, R., M. Richter, N. Möller, S. Ziesemer, I. Eiffler, C. Müller, and J.P. Hildebrandt. (2016). ATP Release from Human Airway Epithelial Cells Exposed to Staphylococcus aureus Alpha-Toxin. Toxins (Basel) 8:.

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Comai, M., M. Dalla Serra, M. Coraiola, S. Werner, D.A. Colin, H. Monteil, G. Prévost, and G. Menestrina. (2002). Protein engineering modulates the transport properties and ion selectivity of the pores formed by staphylococcal γ-haemolysins in lipid membranes. Mol. Microbiol. 44: 1251-1267.

Cooney, J., Z. Kienle, T.J. Foster, and P.W. O’Toole. (1993). The gamma-hemolysin locus of Staphylococcus aureus comprises three linked genes, two of which are identical to the genes for the F and S components of leukocidin. Infect. Immun. 61: 768-771.

Cracknell JA., Japrung D. and Bayley H. (2013). Translocating kilobase RNA through the Staphylococcal alpha-hemolysin nanopore. Nano Lett. 13(6):2500-5.

Dong, J., J. Qiu, Y. Zhang, C. Lu, X. Dai, J. Wang, H. Li, X. Wang, W. Tan, M. Luo, X. Niu, and X. Deng. (2013). Oroxylin A inhibits hemolysis via hindering the self-assembly of α-hemolysin heptameric transmembrane pore. PLoS Comput Biol 9: e1002869.

Frey, J., A. Johansson, S. Bürki, E.M. Vilei, and K. Redhead. (2012). Cytotoxin CctA, a major virulence factor of Clostridium chauvoei conferring protective immunity against myonecrosis. Vaccine 30: 5500-5505.

Furini, S., C. Domene, M. Rossi, M. Tartagni, and S. Cavalcanti. (2008). Model-based prediction of the α-hemolysin structure in the hexameric state. Biophys. J. 95: 2265-2274.

Gurnev, P.A. and E.M. Nestorovich. (2014). Channel-forming bacterial toxins in biosensing and macromolecule delivery. Toxins (Basel) 6: 2483-2540.

Hammerstein, A.F., L. Jayasinghe, and H. Bayley. (2011). Subunit dimers of α-hemolysin expand the engineering toolbox for protein nanopores. J. Biol. Chem. 286: 14324-14334.

Hardy, S.P., T. Lund, and P.E. Granum. (2001). CytK toxin of Bacillus cereus forms pores in planar lipid bilayers and is cytotoxic to intestinal epithelia. FEMS Microbiol. Letts. 197: 47-51.

Jayasinghe, L. and H. Bayley. (2005). The leukocidin pore: evidence for an octamer with four LukF subunits and four LukS subunits alternating around a central axis. Protein. Sci. 14: 2550-2561.

Jayasinghe, L., G. Miles, and H. Bayley. (2006). Role of the amino latch of staphylococcal α-hemolysin in pore formation: a co-operative interaction between the N terminus and position 217. J. Biol. Chem. 281: 2195-2204.

Keyburn, A.L., J.D. Boyce, P. Vaz, T.L. Bannam, M.E. Ford, D. Parker, A. Di Rubbo, J.I. Rood, and R.J. Moore. (2008). NetB, a new toxin that is associated with avian necrotic enteritis caused by Clostridium perfringens. PLoS Pathog 4: e26.

Koop, G., M. Vrieling, D.M. Storisteanu, L.S. Lok, T. Monie, G. van Wigcheren, C. Raisen, X. Ba, N. Gleadall, N. Hadjirin, A.J. Timmerman, J.A. Wagenaar, H.M. Klunder, J.R. Fitzgerald, R. Zadoks, G.K. Paterson, C. Torres, A.S. Waller, A. Loeffler, I. Loncaric, A.E. Hoet, K. Bergström, L. De Martino, C. Pomba, H. de Lencastre, K. Ben Slama, H. Gharsa, E.J. Richardson, E.R. Chilvers, C. de Haas, K. van Kessel, J.A. van Strijp, E.M. Harrison, and M.A. Holmes. (2017). Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus. Sci Rep 7: 40660.

Lund, T., M.L. De Buyser, and P.E. Granum. (2000). A new cytotoxin from Bacillus cereus that may cause necrotic enteritis. Mol. Microbiol. 38: 254-261.

Mehdizadeh Gohari, I., E.K. Brefo-Mensah, M. Palmer, P. Boerlin, and J.F. Prescott. (2018). Sialic acid facilitates binding and cytotoxic activity of the pore-forming Clostridium perfringens NetF toxin to host cells. PLoS One 13: e0206815.

Menestrina, G., M. Dalla Serra, and G. Prévost. (2001). Mode of action of beta-barrel pore-forming toxins of the staphylococcal alpha-hemolysin family. Toxicon 39: 1661-1672.

Montoya, M. and E. Gouaux. (2003). β-Barrel membrane protein folding and structure viewed through the lens of α-hemolysin. Biochim. Biophys. Acta 1609: 19-27.

Movileanu, L., J.P. Schmittschmitt, J.M. Scholtz, and H. Bayley. (2005). Interactions of peptides with a protein pore. Biophys. J. 89: 1030-1045.

Prévost, G., L. Mourey, D.A. Colin, and G. Menestrina. (2001). Staphylococcal pore-forming toxins. Curr. Top. Microbiol. Immunol. 257: 53-83.

Qing, Y., S.A. Ionescu, G.S. Pulcu, and H. Bayley. (2018). Directional control of a processive molecular hopper. Science 361: 908-912.

Ray, A., L.N. Kinch, M. de Souza Santos, N.V. Grishin, K. Orth, and D. Salomon. (2016). Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus. MBio 7:.

Reyes-Robles, T. and V.J. Torres. (2016). Staphylococcus aureus Pore-Forming Toxins. Curr Top Microbiol Immunol. [Epub: Ahead of Print]

Reyes-Robles, T., A. Lubkin, F. Alonzo, 3rd, D.B. Lacy, and V.J. Torres. (2016). Exploiting dominant-negative toxins to combat Staphylococcus aureus pathogenesis. EMBO Rep 17: 428-440.

Roblin, P., V. Guillet, O. Joubert, D. Keller, M. Erard, L. Maveyraud, G. Prévost, and L. Mourey. (2008). A covalent S-F heterodimer of leucotoxin reveals molecular plasticity of β-barrel pore-forming toxins. Proteins 71: 485-496.

Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi, and G.B. Young. (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56.

Shah, J., F. Rouaud, D. Guerrera, E. Vasileva, L.M. Popov, W.L. Kelley, E. Rubinstein, J.E. Carette, M.R. Amieva, and S. Citi. (2018). A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote α-Toxin Cytotoxicity. Cell Rep 25: 2132-2147.e7.

Song, L., M.R. Hobaugh, C. Shustak, S. Cheley, H. Bayley, and J.E. Gouaux. (1996). Structure of staphylococcal α-hemolysin, a heptameric transmembrane pore. Science 274: 1859-1866.

Steinporsdottir, V., V. Frithriksdottir, E. Gunnarsson, and O.S. Andresson. (1995). Expression and purification of Clostridium perfringens beta-toxin glutathione S-transferase fusion protein. FEMS Microbiol. Lett. 130: 273-278.

Sugawara T., Yamashita D., Kato K., Peng Z., Ueda J., Kaneko J., Kamio Y., Tanaka Y. and Yao M. (2015). Structural basis for pore-forming mechanism of staphylococcal alpha-hemolysin. Toxicon. 108:226-31.

Sugawara-Tomita, N., T. Tomita, and Y. Kamio. (2002). Stochastic assembly of two-component staphylococcal γ-hemolysin into heteroheptameric transmembrane pores with alternate subunit arrangements in ratios of 3:4 and 4:3. J. Bacteriol. 184: 4747-4756.

Supersac, G., G. Prévost, and Y. Piemont. (1993). Sequencing of leucocidin R from Staphylococcus aureus p83 suggests that Staphylococcal leucocidins and gamma-hemolysin are members of a single, two-component family of toxins. Infect. Immun. 61: 580-587.

Tilley, S.J. and H.R. Saibil. (2006). The mechanism of pore formation by bacterial toxins. Curr. Opin. Struct. Biol. 16: 230-236.

Tomita, N., K. Abe, Y. Kamio, and M. Ohta. (2011). Cluster-forming property correlated with hemolytic activity by staphylococcal γ-hemolysin transmembrane pores. FEBS Lett. 585: 3452-3456.

Vécsey-Semjén, B., Y.K. Kwak, M. Högbom, and R. Möllby. (2010). Channel-forming abilities of spontaneously occurring α-toxin fragments from Staphylococcus aureus. J. Membr. Biol. 234: 171-181.

Wolfe, A.J., M.M. Mohammad, S. Cheley, H. Bayley, and L. Movileanu. (2007). Catalyzing the translocation of polypeptides through attractive interactions. J. Am. Chem. Soc. 129: 14034-14041.

Yamashita, D., T. Sugawara, M. Takeshita, J. Kaneko, Y. Kamio, I. Tanaka, Y. Tanaka, and M. Yao. (2014). Molecular basis of transmembrane β-barrel formation of staphylococcal pore-forming toxins. Nat Commun 5: 4897.

Yamashita, K., Y. Kawai, Y. Tanaka, N. Hirano, J. Kaneko, N. Tomita, M. Ohta, Y. Kamio, M. Yao, and I. Tanaka. (2011). Crystal structure of the octameric pore of staphylococcal γ-hemolysin reveals the β-barrel pore formation mechanism by two components. Proc. Natl. Acad. Sci. USA 108: 17314-17319.

Yannakopoulou, K., L. Jicsinszky, C. Aggelidou, N. Mourtzis, T.M. Robinson, A. Yohannes, E.M. Nestorovich, S.M. Bezrukov, and V.A. Karginov. (2011). Symmetry requirements for effective blocking of pore-forming toxins: comparative study with α-, β-, and γ-cyclodextrin derivatives. Antimicrob. Agents Chemother. 55: 3594-3597.

Zhao, H., F. Hu, S. Jin, X. Xu, Y. Zou, B. Ding, C. He, F. Gong, and Q. Liu. (2016). Typing of Panton-Valentine Leukocidin-Encoding Phages and lukSF-PV Gene Sequence Variation in Staphylococcus aureus from China. Front Microbiol 7: 1200.

Ziesemer, S., N. Möller, A. Nitsch, C. Müller, A.G. Beule, and J.P. Hildebrandt. (2019). Sphingomyelin Depletion from Plasma Membranes of Human Airway Epithelial Cells Completely Abrogates the Deleterious Actions of S. aureus Alpha-Toxin. Toxins (Basel) 11:.

Examples:

TC#NameOrganismal TypeExample
1.C.3.1.1

α-Hemolysin (alpha haemolysin; Hly; Hla; α-toxin). Fragments (13-293 aas) form heptamers like the native full length protein, but a fragment with aas 72-293 formed heptamers, octamers and nonamers. All formed Cl- permeable β-barrel channels (Vécsey-Semjén et al., 2010). The 3-d structure is available (PDB#7AHL). Both symmetry and size of cyclodextrin inhibitors and the toxin pore are important for effective inhibition (Yannakopoulou et al., 2011).  Oxoxylin A inhibits hemolysis by hindering self assembly of the hepatmeric pore in which two β-strands are contributed by each subunit (Song et al. 1996; Dong et al. 2013).  Applications of pore-forming α-haemolysin include small- and macromolecule-sensing, targeted cancer therapy, and drug delivery (Gurnev and Nestorovich 2014). Sugawara et al. 2015 studied pore formation. Structural comparisons among monomer, prepore and pore revealed a series of motions in which the N-terminal amino latch released upon oligomerization destroys its own key hydrogen bond betweem Asp45 and Try118. This action initiates the protrusion of the prestem. A Y118F mutant and the N-terminal truncated mutant markedly decreased the hemolytic activity, indicating the importance of the key hydrogen bond and the N-terminal amino latch for pore formation. A dynamic molecular mechanism of pore formation was proposed (Sugawara et al. 2015). Release of ATP from cells may occur directly through transmembrane pores formed by α-toxin (Baaske et al. 2016). The amino latch of staphylococcal alpha-hemolysin functions in pore formation via an co-operative interaction between the N terminus and position 217 (Jayasinghe et al. 2006).

PLEKHA7 and other junctional proteins are host factors mediating death by S. aureus alpha-toxin. ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C-terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. ADAM10 is locked at junctions through binding of its cytoplasmic C terminus to afadin. Junctionally clustered ADAM10 supports the efficient formation of stable toxin pores. Disruption of the PLEKHA7-PDZD11 complex inhibits ADAM10 and toxin junctional clustering. This promotes toxin pore removal from the cell surface through an actin- and macropinocytosis-dependent process, resulting in cell recovery from initial injury and survival. Thus, a dock-and-lock molecular mechanism targets ADAM10 to junctions, providing a paradigm for how junctions may regulate transmembrane receptors through their clustering (Shah et al. 2018).

Gram-positive bacteria

α-hemolysin of Staphylococcus aureus

 
Examples:

TC#NameOrganismal TypeExample
1.C.3.2.1

Hemolysin II

Gram-positive bacteria

Hemolysin II of Bacillus cereus

 
1.C.3.2.2

β-toxin

Gram-positive bacteria β-toxin of Clostridium perfringens
 
1.C.3.2.3Cytotoxin Gram-positive bacteria Cytotoxin CytK of Bacillus cereus
 
1.C.3.2.4

Necrotic enteritis toxin B precursor, NetB (Keyburn et al., 2008)

BacteriaNetB of Clostridium perfringens (A8ULG6)
 
1.C.3.2.5

CctA (Clostridium chauvoei toxin A; 317 aas) is the main cytotoxic and haemolytic substance secreted by C. chauvoei.  Vaccination of guinea pigs with CctA in the form of a fusion protein with the E. coli heat labile toxin B subunit (rCctA::LTB) as a peptide adjuvant protected the animals against challenge with spores of virulent C. chauvoei., (Frey et al. 2012).

Firmicutes

Cytotoxin of Clostridium chauvoei


 
 
1.C.3.2.6

Necrotizing enteritis toxin, NetF, of 305 aas.  NetF-producing type A Clostridium perfringens is an important cause of canine and foal necrotizing enteritis. NetF, related to the β-sheet pore-forming Leukocidin/Hemolysin superfamily, is considered a major virulence factor for this disease. The NetF receptor is probably a sialic acid-containing glycoprotein (Mehdizadeh Gohari et al. 2018).

NetF of Clostridium perfringens

 
Examples:

TC#NameOrganismal TypeExample
1.C.3.3.1Leucocidin/Hemolysin family member, LHFGram-negative bacteria LHF member of Vibrio species Ex25, (EDN58324)
 
1.C.3.3.2

Leucocidin/Hemolysin toxin family member.  90% identical to a Leukocidin of Vibrio proteolyticus of 305 aas that plays an important role in virulence (Ray et al. 2016).

Gram-negative bacteria

V12G01_16082 of Vibrio alginolyticus (Q1V718)

 
Examples:

TC#NameOrganismal TypeExample
1.C.3.4.1

Leucocidin chain F.  3-D structures of the prepore reveal that this is substantially different from the pore structure.  The structures revealed a disordered bottom half of the beta-barrel corresponding to the transmembrane region, and a rigid upper extramembrane half (Yamashita et al. 2014). LukF can form an octameric pore with 4 subunits of LukF and 4 subunits of LukS (TC# 1.C.3.4.3) (Jayasinghe and Bayley 2005).  Panton-Valentine leukocidin (PVL, encoded by lukSF-PV genes) is a bi-component and pore-forming toxin carried by different staphylococcal bacteriophages (Zhao et al. 2016).

Gram-positive firmicutes

Leucocidin chain F (LukF) of Staphylococcus aureus (Q53747)

 
1.C.3.4.2

Two component β-barrel γ-haemolysin, HlgA·HlgB. Tomita et al. (2011) reported that Hlg2 and LukF form a complex, and that Hlg pores form clusters that release hemoglobin from erythrocytes. The crystal structure of this octameric pore (PDB# 3B07; 2QK7) reveals the beta-barrel pore formation mechanism by the two components (Yamashita et al., 2011).  Dominant-negative mutant toxins may provide novel therapeutics to combat S. aureus infection (Reyes-Robles et al. 2016).  S. aureus beta-barrel pore-forming cytotoxins, including the identification of the toxin receptors on host cells, and their roles in pathogenesis have been reviewed (Reyes-Robles and Torres 2016).

Gram-positive bacteria

HlgA·HlgB of Staphylococcus aureus

 
1.C.3.4.3

Two component β-barrel γ-haemolysin, HlgC·HlgB. HglC is identical to Leucocidin chain S (LukS) (P31716), and HlgB is identical to the HlgB protein listed under TC# 1.C.3.4.2 (Roblin et al. 2008). The pore-forming regions are initially folded up on the surfaces of the soluble precursors. To create the transmembrane pores, these regions must extend and refold into membrane-inserted beta-barrels (Tilley and Saibil 2006).

Gram-positive bacteria

HlgC·HlgB of Staphylococcus aureus

 
1.C.3.4.4

Equid-adapted leukocidin PQ, LukPQ, of 311 (LukP) and 326 aas (LukQ), respectively (Koop et al. 2017).

LukPQ of Staphylococcus aureus

 
1.C.3.4.5

Beta-channel-forming cytolysin, the  synergohymenotropic toxin, of 310 aas.  Bacterial infections from Staphylococcus pseudintermedius are the most common cause of skin infections (pyoderma) affecting dogs. Two component pore-forming leukocidins are a family of potent toxins secreted by staphylococci and consist of S (slow) and F (fast) components. They impair the innate immune system, the first line of defense against these pathogens. Seven different leukocidins have been characterized in Staphylococcus aureus, some of which are host and cell specific. Abouelkhair et al. 2018 identified two proteins, named "LukS-I" and "LukF-I", encoded on a degenerate prophage contained in the genome of S. pseudintermedius isolates. The killing effect of recombinant S. pseudintermedius LukS-I together with LukF-I on canine polymorphonuclear leukocytes depended on both constituents of the two-component pore-forming leukocidin.

LukS-I/LukF-I of Staphylococcus pseudintermedius

 
Examples:

TC#NameOrganismal TypeExample