Pneumococcal_adaptation_in_COPD_Spain

Invasive pneumococcal disease (IPD) is associated to high morbidity and mortality rates worldwide affecting mainly to children under 5 years old and adults aged >65. Smoking enhances the infection of the respiratory tract and the development of IPD because it promotes the colonization of the lungs therefore contributes to acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). The Spanish Pneumococcal Reference Laboratory and Microbiology Department of Bellvitge Hospital in Barcelona have a large collection of pneumococcal clinical isolates of different serotypes from patients suffering COPD or IPD. In the case of COPD, a common pattern is that these patients develop recurrent pneumococcal pneumonia with multiple episodes due to the same clone (by serotype and MLST). The average time between episodes was 210 days (range, 30 to 531 days), and the average time between first and last episodes was 582 days. One possibility is that the strains from COPD patients (that have been long term active smokers), might have evolved with the advantage to avoid more efficiently the host immune response leading to this persistent phenotype. We have compared the recognition by different complement components as well as by phagocytic cells (neutrophils and alveolar macrophages) persistent COPD isolates and IPD isolates of the same serotypes and MLSTs. For this study, we have investigated 5 isolates each from COPD and IPD belonging to serotypes 11A and 16F that are not-included in the current pneumococcal conjugate vaccines, are associated with drug resistance and are increasing since the introduction of the current PCVs. Our data suggest that pneumococcal strains from COPD patients have an increased ability to avoid the host immune response compared to IPD strains potentially explaining the persistent phenotype. In addition, using lung epithelial cells and a murine model of pneumococcal pneumonia, we have observed that COPD isolates have an impaired ability to invade the lung and disseminate to the systemic circulation in comparison to IPD isolates. We hypothesise that exposure to cigarette smoke in COPD isolates might be beneficial for developing a chronic phenotype by increasing the resistance to the recognition by the host immune response, although it also might be detrimental for the invasiveness. Further, we grew several IPD strains in the presence of cigarette smoke extract (CSE) and we compared the recognition by the host immune response. Our results showed that IPD strains exposed to CSE had an increased ability to avoid the host immune response confirming that pneumococcal exposure to CSE allow the IPD strains to behave as the COPD strains. These results indicate that exposure of S. pneumoniae to cigarette smoke might induce genetic changes that increase the resistance to the host immune response. This is important from the clinical perspective, as the pneumococcal strains living in a smoke environment, such as the lungs of COPD patients, might be more resistant to be completely eradicated even with a proper antimicrobial therapy. Strains that had been converted to COPD phenotype through CSE exposure were grown in tissue culture medium lacking CSE for several generations. The COPD phenotype was not altered suggested a stable genetic adaptation. We propose to sequence the genomes of the 5 isolates from COPD, IPD and ‘IPD exposed to CSE’ for serotypes 11A and 16F (total 30 isolates). We would also like to sequence 50 isolates from COPD patients representing a broad selection of serotypes to search for general genetic associations with this clinical phenotype.