The Yin and Yang of Streptococcus Lung Infections in Cystic Fibrosis: a Model for Studying Polymicrobial Interactions

Abstract

The streptococci are increasingly recognized as a core component of the cystic fibrosis (CF) lung microbiome, yet the role that they play in CF lung disease is unclear. The presence of the Streptococcus milleri group (SMG; also known as the anginosus group streptococci [AGS]) correlates with exacerbation when these microbes are the predominant species in the lung. In contrast, microbiome studies have indicated that an increased relative abundance of streptococci in the lung, including members of the oral microflora, correlates with impacts on lung disease less severe than those caused by other CF-associated microflora, indicating a complex role for this genus in the context of CF. Recent findings suggest that streptococci in the CF lung microenvironment may influence the growth and/or virulence of other CF pathogens, as evidenced by increased virulence factor production by Pseudomonas aeruginosa when grown in coculture with oral streptococci. Conversely, the presence of P. aeruginosa can enhance the growth of streptococci, including members of the SMG, a phenomenon that could be exacerbated by the fact that streptococci are not susceptible to some of the frontline antibiotics used to treat P. aeruginosa infections. Collectively, these studies indicate the necessity for further investigation into the role of streptococci in the CF airway to determine how these microbes, alone or via interactions with other CF-associated pathogens, might influence CF lung disease, for better or for worse. We also propose that the interactions of streptococci with other CF pathogens is an ideal model to study clinically relevant microbial interactions.

From genotype to phenotype: adaptations of Pseudomonas aeruginosa to the cystic fibrosis environment

“…Moreover, a range of microbial interactions can either limit or promote P. aeruginosa persistence and, thus, adaptation within CF lung infections [156–158, 160–162]. In line with this, the presence of Staphylococcus aureus has been shown to promote P.…”

“…Besides pathogens, the role of the normal lung microbiota is increasingly considered since commensal anaerobes have been shown to impact the antibiotic resistance and virulence of P. aeruginosa [161, 162]. Thus, the presence of these micro-organisms may influence establishment and adaptation of P.…”

Availability of Zinc Impacts Interactions between Streptococcus sanguinis and Pseudomonas aeruginosa in Coculture

“…An example of such microbial interactions includes the CF-associated streptococcal species, the presence of which may influence the growth and/or virulence of other CF pathogens, including those of the important pathogen Pseudomonas aeruginosa (12,13). In turn, P. aeruginosa can impact the growth and/or persistence of streptococci (8)(9)(10)14), with the net impact of these interactions resulting in exacerbation in some cases (4,(15)(16)(17) or in less severe loss of lung function under other circumstances (11,16,(18)(19)(20)(21). Thus, the impact of such polymicrobial interactions on host outcomes is complex in the clinical setting.…”

The Microbiome in Cystic Fibrosis Pulmonary Disease

“…The "culturomics" extended-culture approach can culture bacteria previously considered "uncultivable" [48]. It also explores potential microbial interactions identified in meta-genetic studies and characterizes bacterial metabolites of interest [49][50][51]. In CF, extensive culture-enriched airway microbiome profiling identified bacterial families, such as Ruminococcaceae or Bacteriovoracaceae, in CF sputa not detected by 16S rDNA sequencing alone [52].…”