• Identification of core genes involved in Streptococcus pneumoniae host-pathogen interactions under diverse infections, and their potential as therapeutic targets

      D'Mello, Adonis; 0000-0001-6995-3617; Tettelin, Hervé (2021)
      Streptococcus pneumoniae (the pneumococcus) is a human-specific opportunistic pathogen that asymptomatically colonizes the nasopharynx. It is the leading cause of otitis media, communityacquired pneumonia, bacteremia and meningitis, as it can spread from the nasopharynx. It has been estimated that ~500,000 children under the age of 5 die annually due to pneumococcal infection and pneumococcal bacteremia and meningitidis has over 60% mortality rates in the elderly. It has also been established that influenza A co-infections enhance the progression from asymptomatic colonization to invasive disease, with clinically worsened outcomes. Utilization of antibiotics and pneumococcal conjugate vaccines has resulted in the rise of antibiotic resistance and emergence of non-vaccine serotypes, requiring identification of novel therapeutic targets. We hypothesized that there exist pneumococcal conserved genes, that are involved in these diverse forms of colonization, infection, and influenza co-infection. We sought to identify such genes using a combination of in silico, in vivo and ex vivo approaches. Through pangenomics and reverse vaccinology (in silico), and multi-species transcriptomics on a mouse model of pneumococcal colonization and invasive disease (in vivo), and a primary human lung epithelial model of pneumococcal and influenza co-infection (ex vivo), we observed mechanisms underlying diverse host-pathogen interactions and identified novel potential avenues for therapy from both the host and bacterial perspectives.