BACTERIAL SELECTION IN THE LRT
Lung microbiome studies suggest that bacteria colonizing the LRT overlap with those found in the URT, but that the abundance of organisms is quite low [13], and their role in pneumonia etiology has yet to be explored. To colonize the LRT, an organism must overcome mucociliary clearance and phagocytosis by resident alveolar macrophages, neutrophils and monocyte-derived macrophages [37, 38], but many URT pathogens have developed strategies to overcome these barriers. H. influenzae, Mycoplasma pneumoniae and Bordetella pertussis resist mucociliary clearance by impairing ciliary function. Streptococcus pyogenes, Streptococcus agalactiae, H. influenzae, Neisseria meningitidis and S. pneumoniae possess capsules that resist phagocytosis [37]. Streptococcus pneumoniae, the leading cause of pneumonia [39], is characterized by over 90 serotypes differentiated by variations in the bacterial polysaccharide capsule [40, 41] and associated with different propensities of invasive potential [42]. In addition to protecting against phagocytosis, the capsule prevents clearance by mucous secretion and restricts autolysis [43]. Other species, including S. aureus, release anti-opsonizing proteins and possess surface protein A to evade phagocytosis. Furthermore, S. aureus secretes leukotoxins that lyse leukocytes and express superantigens that hinder immune response (reviewed by Naber et al. [44]).
The crucial role these various mechanisms play in determining respiratory disease is demonstrated by contrasting M. catarrhalis with S. pneumoniae. Similar to S. pneumoniae, M. catarrhalis is a primary carriage species estimated to colonize between 31% and 50% of children <2 years in the USA [45] and frequently causes URT infections, such as acute otitis media. However, unlike S. pneumoniae, M. catarrhalis rarely causes pneumonia [46], suggesting that differences in mechanisms of pathogenicity may be the explanation.