The impact of air pollution on respiratory bacteria in Chronic Obstructive Pulmonary Disease

Air pollution is the single largest environmental health risk worldwide. Exposure to the most harmful component of air pollution, particular matter (PM), has been linked with non-communicable diseases including chronic obstructive pulmonary disease (COPD) - the third leading cause of death worldwide. Exposure to PM is one of the biggest risk factors for COPD disease exacerbations, that are frequently linked with bacterial infection by Haemophilus influenzae and Moraxella catarrhalis. Whether infection is a cause or consequence of disease exacerbations remains unclear. It has been shown that behaviour of Staphylococcus aureus and Streptococcus pneumoniae is directly impacted by exposure to PM, which could be significant for COPD patients, with disease decline being linked to PM exposure and bacterial infection. The purpose of this study was to elucidate the effects of PM on H. influenzae and M. catarrhalis.

H. influenzae that were exposed to black carbon (BC) showed a significant iron-uptake response, potentially linked with the observed increase in epithelial cell adhesion through the upregulation of protein F, that is known to facilitate binding to respiratory epithelium. The ability of PM to cause significant changes to bacterial behaviour was also demonstrated by the stress response exhibited by M. catarrhalis. Heat shock proteins regulated by sigma factor 32 were upregulated when exposed to BC, showing the potential of PM to influence specific genetic regulators.

Also in this thesis, the relationship between respiratory microbiome commensals and pathogens on the integrity of the respiratory epithelium was explored. Prevotella spp. abundance has been linked with markers of epithelial integrity in COPD patient populations, while M. catarrhalis has been linked with disease decline and increased inflammation. The potential beneficial properties of Prevotella spp. on epithelial integrity were explored using a model of respiratory epithelium, finding that P. melaninogenica has a weaker potential to damage epithelial integrity than M. catarrhalis.