A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients

Sibley, Christopher D.; Parkins, Michael D.; Rabin, Harvey; Duan, Kangmin; Nørgaard, Jens Christian; Surette, Michael G.

doi:10.1073/pnas.0804326105

Cited by 301 publications

(327 citation statements)

References 57 publications

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“…This has been suggested previously by clinical observations that elimination of Streptococcus milleri, which is a member of the CF lung microbiota associated with severe exacerbations, led to decreased P. aeruginosa virulence (Sibley et al, 2008b). Despite the relatively low microbial densities present in healthy lungs (Dickson and Huffnagle, 2015), alteration of the pulmonary microenvironment to favor a microbial community that is easier to clear may be a promising approach against pulmonary pathogens, which warrant further investigations.…”

mentioning

confidence: 67%

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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confidence: 67%

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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“…Instead, it's likely that this body site harbours an indigenous microbiota whose members behave differently, depending on factors such as their location in the body (Blaser and Falkow, 2009), bacterial community disturbance (Lynch, 2013), environmental pressures (Feldman and Anderson, 2013) and/or immune responses in the host (Starkey et al, 2013). Unlike many acute infectious diseases where a single microbe can be targeted and eradicated, lung infections are often polymicrobial (Bakaletz, 2004;Han et al, 2012;Huang et al, 2012Huang et al, , 2014Dickson et al, 2013) and the organisms recovered from respiratory and invasive infections are often a mixture of common URT microbes (Laupland et al, 2000, Sibley et al, 2008. Respiratory infections have a higher impact on health worldwide than all other infectious diseases combined (Mizgerd, 2006) and mortality rates associated with lung infections have not significantly improved in over 50 years (Mizgerd, 2008).…”

Section: Introductionmentioning

confidence: 99%

Culture and molecular-based profiles show shifts in bacterial communities of the upper respiratory tract that occur with age

et al. 2015

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The upper respiratory tract (URT) is a crucial site for host defense, as it is home to bacterial communities that both modulate host immune defense and serve as a reservoir of potential pathogens. Young children are at high risk of respiratory illness, yet the composition of their URT microbiota is not well understood. Microbial profiling of the respiratory tract has traditionally focused on culturing common respiratory pathogens, whereas recent culture-independent microbiome profiling can only report the relative abundance of bacterial populations. In the current study, we used both molecular profiling of the bacterial 16S rRNA gene and laboratory culture to examine the bacterial diversity from the oropharynx and nasopharynx of 51 healthy children with a median age of 1.1 years (range 1-4.5 years) along with 19 accompanying parents. The resulting profiles suggest that in young children the nasopharyngeal microbiota, much like the gastrointestinal tract microbiome, changes from an immature state, where it is colonized by a few dominant taxa, to a more diverse state as it matures to resemble the adult microbiota. Importantly, this difference in bacterial diversity between adults and children accompanies a change in bacterial load of three orders of magnitude. This indicates that the bacterial communities in the nasopharynx of young children have a fundamentally different structure from those in adults and suggests that maturation of this community occurs sometime during the first few years of life, a period that includes ages at which children are at the highest risk for respiratory disease.

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“…These microenvironments allow for the application of fundamental principles of microbial ecology (Yang et al, 2011;Conrad et al, 2012). For example, synergistic and antagonistic behavior between different CF pathogens has been described (Duan et al, 2003;Harrison, 2007;Sibley et al, 2008;Mitchell et al, 2010;Yang et al, 2011;Venkataraman et al, 2014), and the microbial community has been proposed to contain stable and disturbed states, much like those in classical ecology (Conrad et al, 2012). Known chemical characteristics of the CF lung include lowered pH (Tate et al, 2002;Pezzulo et al, 2012), low oxygen tensions (Worlitzsch et al, 2002) and high levels of amino acids, nitrate, iron and phenazines (Grasemann et al, 1998;Jones et al, 2000;Palmer et al, 2007;Ghio et al, 2012;Hunter et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

et al. 2014

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There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.

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A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients

Cited by 301 publications

References 57 publications

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

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

Culture and molecular-based profiles show shifts in bacterial communities of the upper respiratory tract that occur with age

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

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