| Bacterial infections often involve more than one species. Diverse and dynamic microbial communities characterize the chronic bacterial infections associated with cystic fibrosis (CF) airways. A novel Drosophila model was developed to discern interactions between microbes and the interplay between bacterial communities and the host innate immune system during polymicrobial infection. Using fly survival as readout of relevant exchanges it was determined that interactions within mixed infections could enhance the pathogenicity of a microbial community. Oropharyngeal flora from CF sputa were functionally differentiated to reveal that a large proportion of microorganisms in CF airways can influence the outcome of an infection by synergistically enhancing the virulence of the principal pathogen, Pseudomonas aeruginosa , while being avirulent or even beneficial on their own.;A comprehensive assessment of community composition and dynamics in CF revealed that the airway microbiome is a reservoir of previously unrecognized but clinically relevant organisms. It was common to recover the Streptococcus milleri group (SMG) as the numerically dominant organism at the onset of acute pulmonary exacerbations. Case-based examples demonstrate that antibiotics (without anti-pseudomonal activity) directed at this newly recognized pathogen result in improved clinical outcomes. In patients chronically colonized by conventional pathogens that demonstrate no bacteriological response to standard therapy, alternate approaches that involve managing the airway community can be clinically efficacious.;SMG prevalence in an adult CF cohort was investigated with a novel semi-selective agar, McKay agar, developed for enhanced SMG cultivation. It allowed routine quantification of SMG from 103 to >108 CFU/ml directly from sputum. All members of SMG were detected (Streptococcus anginosus (40.7%), Streptococcus intermedius (34.3%) and Streptococcus constellatus (25%)) with an overall prevalence rate of 40.6%. Without exception, when SMG were cultured at ≤10 7 CFU/ml, patients experienced pulmonary exacerbations requiring clinical intervention.;In opposition to the inclination of microbiology pioneers, most contemporary microbiologists insist that the majority of species cannot be grown in vitro. This modern notion is challenged. A culture-enrichment approach was used to investigate cultivability, which revealed that the vast majority of bacterial species from CF airways could be recovered by culture -- a critical principle for studying the biology of chronic airway infections. |
