The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils

Leïla Staali; Didier André Colin

doi:doi:10.11648/j.ijmb.20200502.13

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The Pore-forming Leukotoxins from S. aureus Involve Ca²⁺ Release-Activated Ca²⁺ Channels and Other Types of Ca²⁺ Channels in Ca²⁺ Entry into Neutrophils

Leïla Staali, Didier André Colin

Published in International Journal of Microbiology and Biotechnology (Volume 5, Issue 2)

Received: 13 April 2020 Accepted: 30 April 2020 Published: 15 May 2020

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Abstract

The pore-forming bi-component leukotoxins from Staphylococcus aureus induce two independent cellular events 1) the formation of trans-membrane pores not permeable to divalent ions and 2) the opening of pre-existing Ca²⁺ channels in human polymorphonuclear neutrophils (PMNs). The influx of Ca²⁺ and Mn²⁺ (Mn²⁺ was used as a Ca²⁺ surrogate) in Fura2-loaded human PMNs was determined by spectrofluorometry techniques. The present study showed that, in the presence of extracellular Ca²⁺, the staphylococcal HlgA/HlgB γ-hemolysin induced a rapid Ca²⁺ release from internal Ca²⁺ stores before the onset of a Mn²⁺ (Ca²⁺) influx. The sustained increase of Ca²⁺ and Mn²⁺ influx was partially inhibited by the ionic blockers of Ca²⁺ Release-Activated Ca²⁺ (CRAC) channels, La³⁺ and Ni²⁺. Furthermore, the incubation of human PMNs with either TMB8 or thapsigargin did inhibit significantly the Ca²⁺ release mediated by leukotoxins simultanously to a clear decrease of Ca²⁺ and Mn²⁺ influx. The internal Ca²⁺ release induced by γ-hemolysin was also inhibited by PMNs pretreatment with a pertussis toxin, NaF, caffeine, ryanodine, cinnarizine and flunarizine and consequently, the Mn²⁺ (Ca²⁺) influx was significantly reduced. Moreover, different Ca²⁺ signaling pathways blockers such as U73122, staurosporine, thyrphostin A9 and okadaic acid were tested on the leukotoxins activity. Taken together, this work provided evidence that, in the presence of extracellular Ca²⁺, bi-component staphylococcal leukotoxins provoked in human PMNs after a specific binding to their membrane receptors, a rapid depletion of internal Ca²⁺ stores mediating a CRAC channels activation. This Ca²⁺-dependent mechanism seems likely to be associated to the heterotrimeric G-proteins activation. Interestingly, in the absence of extracellular Ca²⁺, the staphylococcal leukotoxins tested induced the opening of an important divalent ions (Ca²⁺, Mn²⁺, Ni²⁺) pathway not sensitive to CRAC channels blockers. Consequently, we strongly suggested that other types of Ca²⁺ channels might be involved in bi-component leukotoxins activity, including Ca²⁺ channels dependent on the protein kinase C activation.

Published in	International Journal of Microbiology and Biotechnology (Volume 5, Issue 2)
DOI	10.11648/j.ijmb.20200502.13
Page(s)	55-68
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Pore-forming Toxin, Leukotoxin, γ-hemolysin, Ca²⁺ Channels, S. aureus, Neutrophils, CRAC Channels, Spectrofluorometry

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Leïla Staali, Didier André Colin. (2020). The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils. International Journal of Microbiology and Biotechnology, 5(2), 55-68. https://doi.org/10.11648/j.ijmb.20200502.13

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Leïla Staali; Didier André Colin. The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils. Int. J. Microbiol. Biotechnol. 2020, 5(2), 55-68. doi: 10.11648/j.ijmb.20200502.13

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Leïla Staali, Didier André Colin. The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils. Int J Microbiol Biotechnol. 2020;5(2):55-68. doi: 10.11648/j.ijmb.20200502.13

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@article{10.11648/j.ijmb.20200502.13,
  author = {Leïla Staali and Didier André Colin},
  title = {The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils},
  journal = {International Journal of Microbiology and Biotechnology},
  volume = {5},
  number = {2},
  pages = {55-68},
  doi = {10.11648/j.ijmb.20200502.13},
  url = {https://doi.org/10.11648/j.ijmb.20200502.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijmb.20200502.13},
  abstract = {The pore-forming bi-component leukotoxins from Staphylococcus aureus induce two independent cellular events 1) the formation of trans-membrane pores not permeable to divalent ions and 2) the opening of pre-existing Ca2+ channels in human polymorphonuclear neutrophils (PMNs). The influx of Ca2+ and Mn2+ (Mn2+ was used as a Ca2+ surrogate) in Fura2-loaded human PMNs was determined by spectrofluorometry techniques. The present study showed that, in the presence of extracellular Ca2+, the staphylococcal HlgA/HlgB γ-hemolysin induced a rapid Ca2+ release from internal Ca2+ stores before the onset of a Mn2+ (Ca2+) influx. The sustained increase of Ca2+ and Mn2+ influx was partially inhibited by the ionic blockers of Ca2+ Release-Activated Ca2+ (CRAC) channels, La3+ and Ni2+. Furthermore, the incubation of human PMNs with either TMB8 or thapsigargin did inhibit significantly the Ca2+ release mediated by leukotoxins simultanously to a clear decrease of Ca2+ and Mn2+ influx. The internal Ca2+ release induced by γ-hemolysin was also inhibited by PMNs pretreatment with a pertussis toxin, NaF, caffeine, ryanodine, cinnarizine and flunarizine and consequently, the Mn2+ (Ca2+) influx was significantly reduced. Moreover, different Ca2+ signaling pathways blockers such as U73122, staurosporine, thyrphostin A9 and okadaic acid were tested on the leukotoxins activity. Taken together, this work provided evidence that, in the presence of extracellular Ca2+, bi-component staphylococcal leukotoxins provoked in human PMNs after a specific binding to their membrane receptors, a rapid depletion of internal Ca2+ stores mediating a CRAC channels activation. This Ca2+-dependent mechanism seems likely to be associated to the heterotrimeric G-proteins activation. Interestingly, in the absence of extracellular Ca2+, the staphylococcal leukotoxins tested induced the opening of an important divalent ions (Ca2+, Mn2+, Ni2+) pathway not sensitive to CRAC channels blockers. Consequently, we strongly suggested that other types of Ca2+ channels might be involved in bi-component leukotoxins activity, including Ca2+ channels dependent on the protein kinase C activation.},
 year = {2020}
}

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T1  - The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils
AU  - Leïla Staali
AU  - Didier André Colin
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SN  - 2578-9686
UR  - https://doi.org/10.11648/j.ijmb.20200502.13
AB  - The pore-forming bi-component leukotoxins from Staphylococcus aureus induce two independent cellular events 1) the formation of trans-membrane pores not permeable to divalent ions and 2) the opening of pre-existing Ca2+ channels in human polymorphonuclear neutrophils (PMNs). The influx of Ca2+ and Mn2+ (Mn2+ was used as a Ca2+ surrogate) in Fura2-loaded human PMNs was determined by spectrofluorometry techniques. The present study showed that, in the presence of extracellular Ca2+, the staphylococcal HlgA/HlgB γ-hemolysin induced a rapid Ca2+ release from internal Ca2+ stores before the onset of a Mn2+ (Ca2+) influx. The sustained increase of Ca2+ and Mn2+ influx was partially inhibited by the ionic blockers of Ca2+ Release-Activated Ca2+ (CRAC) channels, La3+ and Ni2+. Furthermore, the incubation of human PMNs with either TMB8 or thapsigargin did inhibit significantly the Ca2+ release mediated by leukotoxins simultanously to a clear decrease of Ca2+ and Mn2+ influx. The internal Ca2+ release induced by γ-hemolysin was also inhibited by PMNs pretreatment with a pertussis toxin, NaF, caffeine, ryanodine, cinnarizine and flunarizine and consequently, the Mn2+ (Ca2+) influx was significantly reduced. Moreover, different Ca2+ signaling pathways blockers such as U73122, staurosporine, thyrphostin A9 and okadaic acid were tested on the leukotoxins activity. Taken together, this work provided evidence that, in the presence of extracellular Ca2+, bi-component staphylococcal leukotoxins provoked in human PMNs after a specific binding to their membrane receptors, a rapid depletion of internal Ca2+ stores mediating a CRAC channels activation. This Ca2+-dependent mechanism seems likely to be associated to the heterotrimeric G-proteins activation. Interestingly, in the absence of extracellular Ca2+, the staphylococcal leukotoxins tested induced the opening of an important divalent ions (Ca2+, Mn2+, Ni2+) pathway not sensitive to CRAC channels blockers. Consequently, we strongly suggested that other types of Ca2+ channels might be involved in bi-component leukotoxins activity, including Ca2+ channels dependent on the protein kinase C activation.
VL  - 5
IS  - 2
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Leïla Staali
Didier André Colin

Bacteriology Institute of Medical Faculty, Louis Pasteur University, Strasbourg, France

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Leïla Staali, Didier André Colin. (2020). The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils. International Journal of Microbiology and Biotechnology, 5(2), 55-68. https://doi.org/10.11648/j.ijmb.20200502.13

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ACS Style

Leïla Staali; Didier André Colin. The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils. Int. J. Microbiol. Biotechnol. 2020, 5(2), 55-68. doi: 10.11648/j.ijmb.20200502.13

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AMA Style

Leïla Staali, Didier André Colin. The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils. Int J Microbiol Biotechnol. 2020;5(2):55-68. doi: 10.11648/j.ijmb.20200502.13

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@article{10.11648/j.ijmb.20200502.13,
  author = {Leïla Staali and Didier André Colin},
  title = {The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils},
  journal = {International Journal of Microbiology and Biotechnology},
  volume = {5},
  number = {2},
  pages = {55-68},
  doi = {10.11648/j.ijmb.20200502.13},
  url = {https://doi.org/10.11648/j.ijmb.20200502.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijmb.20200502.13},
  abstract = {The pore-forming bi-component leukotoxins from Staphylococcus aureus induce two independent cellular events 1) the formation of trans-membrane pores not permeable to divalent ions and 2) the opening of pre-existing Ca2+ channels in human polymorphonuclear neutrophils (PMNs). The influx of Ca2+ and Mn2+ (Mn2+ was used as a Ca2+ surrogate) in Fura2-loaded human PMNs was determined by spectrofluorometry techniques. The present study showed that, in the presence of extracellular Ca2+, the staphylococcal HlgA/HlgB γ-hemolysin induced a rapid Ca2+ release from internal Ca2+ stores before the onset of a Mn2+ (Ca2+) influx. The sustained increase of Ca2+ and Mn2+ influx was partially inhibited by the ionic blockers of Ca2+ Release-Activated Ca2+ (CRAC) channels, La3+ and Ni2+. Furthermore, the incubation of human PMNs with either TMB8 or thapsigargin did inhibit significantly the Ca2+ release mediated by leukotoxins simultanously to a clear decrease of Ca2+ and Mn2+ influx. The internal Ca2+ release induced by γ-hemolysin was also inhibited by PMNs pretreatment with a pertussis toxin, NaF, caffeine, ryanodine, cinnarizine and flunarizine and consequently, the Mn2+ (Ca2+) influx was significantly reduced. Moreover, different Ca2+ signaling pathways blockers such as U73122, staurosporine, thyrphostin A9 and okadaic acid were tested on the leukotoxins activity. Taken together, this work provided evidence that, in the presence of extracellular Ca2+, bi-component staphylococcal leukotoxins provoked in human PMNs after a specific binding to their membrane receptors, a rapid depletion of internal Ca2+ stores mediating a CRAC channels activation. This Ca2+-dependent mechanism seems likely to be associated to the heterotrimeric G-proteins activation. Interestingly, in the absence of extracellular Ca2+, the staphylococcal leukotoxins tested induced the opening of an important divalent ions (Ca2+, Mn2+, Ni2+) pathway not sensitive to CRAC channels blockers. Consequently, we strongly suggested that other types of Ca2+ channels might be involved in bi-component leukotoxins activity, including Ca2+ channels dependent on the protein kinase C activation.},
 year = {2020}
}

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TY  - JOUR
T1  - The Pore-forming Leukotoxins from S. aureus Involve Ca2+ Release-Activated Ca2+ Channels and Other Types of Ca2+ Channels in Ca2+ Entry into Neutrophils
AU  - Leïla Staali
AU  - Didier André Colin
Y1  - 2020/05/15
PY  - 2020
N1  - https://doi.org/10.11648/j.ijmb.20200502.13
DO  - 10.11648/j.ijmb.20200502.13
T2  - International Journal of Microbiology and Biotechnology
JF  - International Journal of Microbiology and Biotechnology
JO  - International Journal of Microbiology and Biotechnology
SP  - 55
EP  - 68
PB  - Science Publishing Group
SN  - 2578-9686
UR  - https://doi.org/10.11648/j.ijmb.20200502.13
AB  - The pore-forming bi-component leukotoxins from Staphylococcus aureus induce two independent cellular events 1) the formation of trans-membrane pores not permeable to divalent ions and 2) the opening of pre-existing Ca2+ channels in human polymorphonuclear neutrophils (PMNs). The influx of Ca2+ and Mn2+ (Mn2+ was used as a Ca2+ surrogate) in Fura2-loaded human PMNs was determined by spectrofluorometry techniques. The present study showed that, in the presence of extracellular Ca2+, the staphylococcal HlgA/HlgB γ-hemolysin induced a rapid Ca2+ release from internal Ca2+ stores before the onset of a Mn2+ (Ca2+) influx. The sustained increase of Ca2+ and Mn2+ influx was partially inhibited by the ionic blockers of Ca2+ Release-Activated Ca2+ (CRAC) channels, La3+ and Ni2+. Furthermore, the incubation of human PMNs with either TMB8 or thapsigargin did inhibit significantly the Ca2+ release mediated by leukotoxins simultanously to a clear decrease of Ca2+ and Mn2+ influx. The internal Ca2+ release induced by γ-hemolysin was also inhibited by PMNs pretreatment with a pertussis toxin, NaF, caffeine, ryanodine, cinnarizine and flunarizine and consequently, the Mn2+ (Ca2+) influx was significantly reduced. Moreover, different Ca2+ signaling pathways blockers such as U73122, staurosporine, thyrphostin A9 and okadaic acid were tested on the leukotoxins activity. Taken together, this work provided evidence that, in the presence of extracellular Ca2+, bi-component staphylococcal leukotoxins provoked in human PMNs after a specific binding to their membrane receptors, a rapid depletion of internal Ca2+ stores mediating a CRAC channels activation. This Ca2+-dependent mechanism seems likely to be associated to the heterotrimeric G-proteins activation. Interestingly, in the absence of extracellular Ca2+, the staphylococcal leukotoxins tested induced the opening of an important divalent ions (Ca2+, Mn2+, Ni2+) pathway not sensitive to CRAC channels blockers. Consequently, we strongly suggested that other types of Ca2+ channels might be involved in bi-component leukotoxins activity, including Ca2+ channels dependent on the protein kinase C activation.
VL  - 5
IS  - 2
ER  -

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