Bacteria that infect the airways of persons with cystic fibrosis (CF) include a group of well-described opportunistic pathogens as well as numerous, mainly obligate or facultative anaerobic species typically not reported by standard sputum culture. We sequenced the V3-V5 hypervariable region of the bacterial 16S rRNA gene in DNA derived from 631 sputum specimens collected from 111 CF patients over 10 years. We describe fluctuations in the relative abundances of typical CF pathogens, as well as anaerobic species, in relation to changes in patients’ clinical state and lung disease stage. Both bacterial community diversity and the relative abundance of anaerobes increased during exacerbation of symptoms (prior to antibiotic treatment), although this trend was not observed uniformly across disease stages. Community diversity and the relative abundance of anaerobic species decreased during antibiotic treatment. These results support current hypotheses regarding the role of anaerobes in CF pulmonary exacerbations and lung disease progression.

Summary. The importance of infection in the pathogenesis of cystic fibrosis (CF) lung disease has been long recognized, and the use of antibiotics targeting bacteria identified in cultures of respiratory specimens has played a critical role in improving outcomes for individuals with CF. Over the past $15 years, the use of culture-independent methods to assess airway microbiology in CF has revealed complex and dynamic CF airway bacterial communities. Recent areas of investigation of the CF lung microbiome have included exploring how bacterial community structures change over time, particularly with respect to disease progression or pulmonary exacerbation, and in response to antibiotic therapies. This review will discuss what has been learned from these studies as well as how these findings offer opportunities to further refine management of CF airway infection. Pediatr Pulmonol. 2015;50:S31-S38.

Mycobacterium abscessus is a rapidly growing mycobacterium increasingly detected in the neutrophil-rich environment of inflamed tissues, including the cystic fibrosis airway. Studies of the immune reaction to M. abscessus have focused primarily on macrophages and epithelial cells, but little is known regarding the neutrophil response despite the predominantly neutrophillic inflammation typical of these infections. In the current study, human neutrophils released less superoxide anion in response to M. abscessus than to Staphylococcus aureus, a pathogen that shares common sites of infection. Exposure to M. abscessus induced neutrophil-specific chemokine and proinflammatory cytokine genes. Although secretion of these protein products was confirmed, the quantity of cytokines released, and both the number and level of gene induction, was reduced compared to S. aureus. Neutrophils mediated killing of M. abscessus, but phagocytosis was reduced when compared to S. aureus, and extracellular DNA was detected in response to both bacteria, consistent with extracellular trap formation. In addition, M. abscessus did not alter cell death compared to unstimulated cells, while S. aureus enhanced necrosis and inhibited apoptosis. However, neutrophils augment M. abscessus biofilm formation. The response of neutrophils to M. abscessus suggests that the mycobacterium exploits neutrophil-rich settings to promote its survival and that the overall neutrophil response was reduced compared to S. aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy.