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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
International Journal of Microbiology and Biotechnology
Volume 5, Issue 2, June 2020, Pages: 55-68
Received: Apr. 13, 2020; Accepted: Apr. 30, 2020; Published: May 15, 2020
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Leïla Staali, Department of Biotechnology, Natural and Life Sciences Faculty, Ahmed Ben Bella Oran1-University, Oran, Algeria; Bacteriology Institute of Medical Faculty, Louis Pasteur University, Strasbourg, France
Didier André Colin, Bacteriology Institute of Medical Faculty, Louis Pasteur University, Strasbourg, France
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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.
Pore-forming Toxin, Leukotoxin, γ-hemolysin, Ca2+ Channels, S. aureus, Neutrophils, CRAC Channels, Spectrofluorometry
To cite this article
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, International Journal of Microbiology and Biotechnology. Vol. 5, No. 2, 2020, pp. 55-68. doi: 10.11648/j.ijmb.20200502.13
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This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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