TY - JOUR
T1 - Streptococcus pneumoniae and Its Virulence Factors H2O2 and Pneumolysin Are Potent Mediators of the Acute Chest Syndrome in Sickle Cell Disease
AU - Gonzales, Joyce
AU - Chakraborty, Trinad
AU - Romero, Maritza
AU - Mraheil, Mobarak Abu
AU - Kutlar, Abdullah
AU - Pace, Betty
AU - Lucas, Rudolf
N1 - Funding Information:
The authors acknowledge funding as follows, Rudolf Lucas was supported by NIH/NHLBI R01 grant HL138410 and by a grant from the Lungen-und Atmungsstiftung, Bern, 3012 Bern, Switzerland. Trinad Chakraborty and Mobarak A Mraheil report support from the DFG through TR84 “Innate Immunity of the lung” for data discussed in this manuscript. Joyce Gonzales and Betty S. Pace were supported by grant HL117684.
Funding Information:
Funding: The authors acknowledge funding as follows, Rudolf Lucas was supported by NIH/NHLBI R01 grant HL138410 and by a grant from the Lungen-und Atmungsstiftung, Bern, 3012 Bern, Switzerland. Trinad Chakraborty and Mobarak A Mraheil report support from the DFG through TR84 “Innate Immunity of the lung” for data discussed in this manuscript. Joyce Gonzales and Betty S. Pace were supported by grant HL117684.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2
Y1 - 2021/2
N2 - Sickle cell disease (SCD) is one of the most common autosomal recessive disorders in the world. Due to functional asplenia, a dysfunctional antibody response, antibiotic drug resistance and poor response to immunization, SCD patients have impaired immunity. A leading cause of hospitalization and death in SCD patients is the acute chest syndrome (ACS). This complication is especially manifested upon infection of SCD patients with Streptococcus pneumoniae (Spn)—a facultative anaerobic Gram-positive bacterium that causes lower respiratory tract infections. Spn has developed increased rates of antibiotics resistance and is particularly virulent in SCD patients. The primary defense against Spn is the generation of reactive oxygen species (ROS) during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn itself produces high levels of the ROS hydrogen peroxide (H2O2) as a virulence strategy. Apart from H2O2, Spn also secretes another virulence factor, i.e., the pore-forming exotoxin pneumolysin (PLY), a potent mediator of lung injury in patients with pneumonia in general and particularly in those with SCD. PLY is released early on in infection either by autolysis or bacterial lysis following the treatment with antibiotics and has a broad range of biological activities. This review will discuss recent findings on the role of pneumococci in ACS pathogenesis and on strategies to counteract the devastating effects of its virulence factors on the lungs in SCD patients.
AB - Sickle cell disease (SCD) is one of the most common autosomal recessive disorders in the world. Due to functional asplenia, a dysfunctional antibody response, antibiotic drug resistance and poor response to immunization, SCD patients have impaired immunity. A leading cause of hospitalization and death in SCD patients is the acute chest syndrome (ACS). This complication is especially manifested upon infection of SCD patients with Streptococcus pneumoniae (Spn)—a facultative anaerobic Gram-positive bacterium that causes lower respiratory tract infections. Spn has developed increased rates of antibiotics resistance and is particularly virulent in SCD patients. The primary defense against Spn is the generation of reactive oxygen species (ROS) during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn itself produces high levels of the ROS hydrogen peroxide (H2O2) as a virulence strategy. Apart from H2O2, Spn also secretes another virulence factor, i.e., the pore-forming exotoxin pneumolysin (PLY), a potent mediator of lung injury in patients with pneumonia in general and particularly in those with SCD. PLY is released early on in infection either by autolysis or bacterial lysis following the treatment with antibiotics and has a broad range of biological activities. This review will discuss recent findings on the role of pneumococci in ACS pathogenesis and on strategies to counteract the devastating effects of its virulence factors on the lungs in SCD patients.
KW - HO
KW - Streptococcus pneumoniae
KW - acute chest syndrome
KW - pneumolysin
KW - sickle cell disease
UR - http://www.scopus.com/inward/record.url?scp=85102605150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102605150&partnerID=8YFLogxK
U2 - 10.3390/TOXINS13020157
DO - 10.3390/TOXINS13020157
M3 - Review article
C2 - 33671422
AN - SCOPUS:85102605150
SN - 2072-6651
VL - 13
JO - Toxins
JF - Toxins
IS - 2
M1 - 157
ER -