Streptococcus pneumoniae and Its Virulence Factors H2O2 and Pneumolysin Are Potent Mediators of the Acute Chest Syndrome in Sickle Cell Disease.

Abstract

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.

• Authors: Joyce Gonzales, Trinad Chakraborty, Maritza Romero, Mobarak Abu Mraheil, Abdullah Kutlar, Betty Pace, Rudolf Lucas
• Journal: Toxins (Toxins (Basel)) Vol. 13 Issue 2 (02 17 2021) ISSN: 2072-6651 [Electronic] Switzerland
• PMID: 33671422 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Streptolysins
• Virulence Factors
• plY protein, Streptococcus pneumoniae
• Hydrogen Peroxide

Topics

• Acute Chest Syndrome (diagnosis, drug therapy, microbiology)
• Anemia, Sickle Cell (complications, diagnosis)
• Animals
• Anti-Bacterial Agents (therapeutic use)
• Bacterial Proteins (metabolism)
• Host-Pathogen Interactions
• Humans
• Hydrogen Peroxide (metabolism)
• Pneumonia, Pneumococcal (diagnosis, drug therapy, microbiology)
• Prognosis
• Risk Factors
• Streptococcus pneumoniae (drug effects, metabolism, pathogenicity)
• Streptolysins (metabolism)
• Virulence
• Virulence Factors (metabolism)