Prevotella intermedia Induces Severe Bacteremic Pneumococcal Pneumonia in Mice with Upregulated Platelet-Activating Factor Receptor Expression

Abstract

dStreptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

Prevotella intermedia and periodontitis are associated with severe asthma

“…27 The bacterial complex is sequentially installed during the process of dental biofilm formation, which favors bacterial succession ranging from a state of oral health (symbiosis) to the triggering of disturbances in the microbiota (dysbiosis), as well as gingival inflammation and, eventually, periodontitis. 32 It is important to note that previous studies have identified P. intermedia in the respiratory tract in association with chronic bronchitis, 33 pneumococcal pneumonia, 34 and pulmonary infections in the context of cystic fibrosis. 15 The central members of the red complex, particularly P. gingivalis, are considered keystone pathogens 29 in the triggering of periodontitis.…”

“…15 In addition, P. intermedia can increase the activity of degradative enzymes, which creates conditions in the bacterial community that favor the progression of periodontitis. 32 It is important to note that previous studies have identified P. intermedia in the respiratory tract in association with chronic bronchitis, 33 pneumococcal pneumonia, 34 and pulmonary infections in the context of cystic fibrosis. 35 It is accordingly possible that this bacterium may also be present in the respiratory tract in association with asthma, In addition, this bacterium is known to induce the production of proteins involved in the proteolytic degradation of the extracellular matrix and basal membrane compounds, for example, MMP-1, MMP-8, and MMP-15 in human periodontal ligament cells.…”

Association of sputum microbiota profiles with severity of community-acquired pneumonia in children

“…When these taxa are identified in children with pneumonia, they are often found in mixed infections [50]. Prevotella intermedia, an oral bacterium, was recently shown to have synergistic effects on S. pneumoniae virulence in murine models of bacteremic pneumonia [51]. Transtrachial aspiration followed by culture has been used to identify anaerobes in 22 Table S3).…”

Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia

“…Finally, interactions between S. pneumoniae and other bacteria may exist. For example, Prevotella intermedia, a major periodontopathic bacterium, induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression [17]. In addition, there is increasing evidence of interactions among S. pneumoniae, H. influenzae, M. catarrhalis, and MSSA in otitis media [18][19][20][21].…”

“…In addition, there has been an increase in investigations focusing on biological interactions between S. pneumoniae and other bacteria [17][18][19][20][21]. However, there has been little evidence regarding the clinical significance of bacterial coinfection in patients with pneumococcal pneumonia.…”