Abstract
Streptococcus pneumoniae, a Gram-positive bacterium, is a major cause of invasive infection-related diseases such as pneumonia and sepsis. In blood, erythrocytes are considered to be an important factor for bacterial growth, as they contain abundant nutrients. However, the relationship between S. pneumoniae and erythrocytes remains unclear. We analyzed interactions between S. pneumoniae and erythrocytes, and found that iron ion present in human erythrocytes supported the growth of Staphylococcus aureus, another major Gram-positive sepsis pathogen, while it partially inhibited pneumococcal growth by generating free radicals. S. pneumoniae cells incubated with human erythrocytes or blood were subjected to scanning electron and confocal fluorescence microscopic analyses, which showed that the bacterial cells adhered to and invaded human erythrocytes. In addition, S. pneumoniae cells were found associated with human erythrocytes in cultures of blood from patients with an invasive pneumococcal infection. Erythrocyte invasion assays indicated that LPXTG motif-containing pneumococcal proteins, erythrocyte lipid rafts, and erythrocyte actin remodeling are all involved in the invasion mechanism. In a neutrophil killing assay, the viability of S. pneumoniae co-incubated with erythrocytes was higher than that without erythrocytes. Also, H2O2 killing of S. pneumoniae was nearly completely ineffective in the presence of erythrocytes. These results indicate that even when S. pneumoniae organisms are partially killed by iron ion-induced free radicals, they can still invade erythrocytes. Furthermore, in the presence of erythrocytes, S. pneumoniae can more effectively evade antibiotics, neutrophil phagocytosis, and H2O2 killing.
Highlights
Severe community-acquired pneumonia reported to be the most common cause of death from infection in developed countries [1]
We found that addition of the iron chelator inhibited the growth of S. aureus with erythrocytes (Fig. 1) and chelator-treated S. aureus did not grow on Tryptic Soy agar
This finding is consistent with previous reports, which noted that iron is essential for S. aureus [26] and its growth in the presence of erythrocytes was significantly inhibited by an iron chelator [18]
Summary
Severe community-acquired pneumonia reported to be the most common cause of death from infection in developed countries [1]. Streptococcus pneumoniae is a Gram-positive bacterium and the main cause of community acquired pneumonia worldwide. Antimicrobial resistance among S. pneumoniae strains is increasing throughout the world [3]. S. pneumoniae has been categorized into at least 91 serotypes based on the antigenic property of its capsule polysaccharide, while a capsule-conjugated vaccine against a subset of pneumococcal serotypes has shown considerable benefits [4]. It has been reported that serotypes not targeted by the vaccine are increasing [5,6], while another study showed that S. pneumoniae can adapt to clinical interventions over a remarkably short period of time because of a high rate of recombination [7]
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