The Cystic Fibrosis Airway Microbiome

Lynch, Susan V.; Bruce, Kenneth D.

doi:10.1101/cshperspect.a009738

Cited by 97 publications

(84 citation statements)

References 23 publications

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“…The CF pulmonary microbiome has identified complex bacterial communities, including traditional pathogens, anaerobic bacteria, and other less known pathogens in lower airways of patients with CF (61,62). There is a lack of similar studies in patients with non-CF bronchiectasis.…”

Section: Discussionmentioning

confidence: 99%

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Yuan

Panchal

Syed

et al. 2013

The Journal of Immunology

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Stomatococcus mucilaginosus is an oral commensal that has been occasionally reported to cause severe infections in immunocompromised patients. There is no information about the pathogenic role of S. mucilaginosus in airway infections. In a cohort of 182 subjects with bronchiectasis, we found that 9% were colonized with S. mucilaginosus in their lower airways by culture growth from bronchoalveolar lavage. To address the pathogenic potential of S.mucilaginosus, we developed a murine model of S. mucilaginosus lung infection. Intratracheal injection of S. mucilaginosus in C57BL/6 mice resulted in a neutrophilic influx with production of proinflammatory cytokines, chemokines, and lipid mediators, mainly PGE2 with induction of cyclooxygenase-2 (COX-2) in the lungs. Presence of TLR2 was necessary for induction of COX-2 and production of PGE2 by S. mucilaginosus. TLR2-deficient mice showed an enhanced clearance of S. mucilaginosus compared with wild-type mice. Administration of PGE2 to TLR2−/− mice resulted in impaired clearance of S. mucilaginosus, suggesting a key role for COX-2–induced PGE2 production in immune response to S. mucilaginosus. Mechanistically, induction of COX-2 in macrophages was dependent on the p38-ERK/MAPK signaling pathway. Furthermore, mice treated with S. mucilaginosus and Pseudomonas aeruginosa showed an increased mortality compared with mice treated with PA103 or S. mucilaginosus alone. Inhibition of COX-2 significantly improved survival in mice infected with PA103 and S. mucilaginosus. These data provide novel insights into the bacteriology and personalized microbiome in patients with bronchiectasis and suggest a pathogenic role for S. mucilaginosus in patients with bronchiectasis.

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Section: Discussionmentioning

confidence: 99%

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Yuan

Panchal

Syed

et al. 2013

The Journal of Immunology

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“…The reader is referred to several recent studies for information on this increasingly important topic. [54][55][56][57] …”

Section: Cf Ipandc Guideline Consensus: 100%mentioning

confidence: 99%

Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update

Saiman

Siegel

LiPuma

et al. 2014

Infect. Control Hosp. Epidemiol.

352

382

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The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF. These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF. These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.

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“…Particularly for chronic lung diseases with frequent bacterial infections, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease, airway microbiome dynamics have been associated with disease progression (Hunter et al, 2012, Pragman et al, 2012Huang et al, 2014). CF predisposes the respiratory tract to polymicrobial infections, and the frequent emergence of Pseudomonas aeruginosa is associated with a reduction in bacterial richness (Lynch and Bruce, 2013;Chmiel et al, 2014). Phenotype and virulence of P. aeruginosa are affected by interactions with the host and cohabiting microbes (Sibley et al, 2008a;Hunter et al, 2012;Venkataraman et al, 2014;Whiteson et al, 2014).…”

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confidence: 99%

The fermentation product 2,3-butanediol alters P. aeruginosa clearance, cytokine response and the lung microbiome

Nguyen

Sharma

et al. 2016

The ISME Journal

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Diseases that favor colonization of the respiratory tract with Pseudomonas aeruginosa are characterized by an altered airway microbiome. Virulence of P. aeruginosa respiratory tract infection is likely influenced by interactions with other lung microbiota or their products. The bacterial fermentation product 2,3-butanediol enhances virulence and biofilm formation of P. aeruginosa in vitro. This study assessed the effects of 2,3-butanediol on P. aeruginosa persistence, inflammatory response, and the lung microbiome in vivo. Here, P. aeruginosa grown in the presence of 2,3-butanediol and encapsulated in agar beads persisted longer in the murine respiratory tract, induced enhanced TNF-α and IL-6 responses and resulted in increased colonization in the lung tissue by environmental microbes. These results led to the following hypothesis that now needs to be tested with a larger study: fermentation products from the lung microbiota not only have a role in P. aeruginosa virulence and abundance, but also on the increased colonization of the respiratory tract with environmental microbes, resulting in dynamic shifts in microbiota diversity and disease susceptibility.

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The Cystic Fibrosis Airway Microbiome

Cited by 97 publications

References 23 publications

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update

The fermentation product 2,3-butanediol alters P. aeruginosa clearance, cytokine response and the lung microbiome

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