Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs

Jorth, Peter; Staudinger, Benjamin J.; Wu, Xia; Hisert, Katherine B.; Hayden, Hillary S.; Garudathri, Jayanthi; Harding, Christopher L.; Radey, Matthew C.; Rezayat, Arash Akhavan; Bautista, Gilbert E.; Berrington, William R.; Goddard, Amanda F.; Zheng, Chen; Angermeyer, Angus; Brittnacher, M.; Kitzman, Jacob O.; Shendure, Jay; Fligner, Corinne L.; Mittler, John E.; Aitken, Moira L.; Manoil, Colin; Bruce, James E.; Yahr, Timothy L.; Singh, Pradeep Kumar

doi:10.1016/j.chom.2015.07.006

Cited by 281 publications

(317 citation statements)

References 45 publications

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“…Most importantly, it does not address the role of oral anaerobes or bacterial nutrient acquisition in late stages of CF disease (Fig 8D). In chronic airway infections, bacterial diversity often declines and lung microbiota becomes predominated by P. aeruginosa [50,51]. Therefore, it is probable that P. aeruginosa does not rely upon mucin fermentation in late stages, but rather contributions from the host inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Evidence and role for bacterial mucin degradation in cystic fibrosis airway disease

Flynn

Niccum

Dunitz

et al. 2016

Preprint

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Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. Author SummaryPersistent CF lung infections are composed of hundreds of microbial taxa whose interactions contribute to respiratory failure. Despite their importance, the complex interplay between the lung microbiota and host environment is poorly understood. For example, the nutrients that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. We reveal that a subset of CF microbiota is capable of fermenting mucins for carbon and energy which, in-turn, can support the carbon demands of other PLOS Pathogens |

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Section: Discussionmentioning

confidence: 99%

Evidence and role for bacterial mucin degradation in cystic fibrosis airway disease

Flynn

Niccum

Dunitz

et al. 2016

Preprint

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“…Diversity, genetic or otherwise, underpins the persistence of P. aeruginosa infections, such as those colonizing the lungs of cystic fibrosis patients (31). In this context, bacterial populations become spatially isolated (58) and are subjected to variations in environmental redox potential (57). Since drug efficacy is largely dependent on the genotype of the target, clonal diversity can lead to further complications when treating bacterial infections with antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Facultative Control of Matrix Production Optimizes Competitive Fitness in Pseudomonas aeruginosa PA14 Biofilm Models

Madsen

Lin

Squyres

et al. 2015

Appl Environ Microbiol

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cAs biofilms grow, resident cells inevitably face the challenge of resource limitation. In the opportunistic pathogen Pseudomonas aeruginosa PA14, electron acceptor availability affects matrix production and, as a result, biofilm morphogenesis. The secreted matrix polysaccharide Pel is required for pellicle formation and for colony wrinkling, two activities that promote access to O 2 . We examined the exploitability and evolvability of Pel production at the air-liquid interface (during pellicle formation) and on solid surfaces (during colony formation). Although Pel contributes to the developmental response to electron acceptor limitation in both biofilm formation regimes, we found variation in the exploitability of its production and necessity for competitive fitness between the two systems. The wild type showed a competitive advantage against a non-Pel-producing mutant in pellicles but no advantage in colonies. Adaptation to the pellicle environment selected for mutants with a competitive advantage against the wild type in pellicles but also caused a severe disadvantage in colonies, even in wrinkled colony centers. Evolution in the colony center produced divergent phenotypes, while adaptation to the colony edge produced mutants with clear competitive advantages against the wild type in this O 2 -replete niche. In general, the structurally heterogeneous colony environment promoted more diversification than the more homogeneous pellicle. These results suggest that the role of Pel in community structure formation in response to electron acceptor limitation is unique to specific biofilm models and that the facultative control of Pel production is required for PA14 to maintain optimum benefit in different types of communities. Most bacteria form multicellular communities called biofilms by producing and encasing themselves in matrices of secreted polymers (1). The National Institutes of Health has estimated that more than half of all bacterial infections involve such biofilm formation, a feature that complicates treatment due to a variety of associated mechanisms that confer increased antibiotic resistance and tolerance in these communities (2). Steep chemical gradients that form within cellular aggregates give rise to microenvironmental heterogeneity; consequently, cells in biofilms exist in diverse physiological states, at least some of which are unique to this lifestyle. For example, in the opportunistic pathogen Pseudomonas aeruginosa PA14, some genes expressed specifically in biofilms are critical for the establishment of lung infections in a mouse model (3). A better understanding of the physiology of biofilm development is required for rational approaches to new therapies for many types of bacterial infections.Using a colony biofilm model, we have found that a primary factor influencing P. aeruginosa PA14 community morphology is the availability of electron acceptors (4-6). As colonies increase in thickness, the formation of O 2 gradients renders the community anoxic at depth and leads to an increase in intr...

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“…This pattern appears to hold in P. aeruginosa following lung infection of a CF patient. From a single inoculating clone, the descendant bacteria evolve into multiple populations with different nutrient requirements, antibiotic resistance, and virulence (198). This within-host diversification is frequently aided by evolution of higher mutation rates (199) and eventually an attenuation of virulence that could foster coexistence among the populations (200,201).…”

Section: Models Of Speciation: Rapidly Speciating Taxa the Speedy Spementioning

confidence: 99%

Transmission in the Origins of Bacterial Diversity, From Ecotypes to Phyla

Cohan

2017

Microbiol Spectr

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Any two lineages, no matter how distant they are now, began their divergence as one population splitting into two lineages that could coexist indefinitely. The rate of origin of higher-level taxa is therefore the product of the rate of speciation times the probability that two new species coexist long enough to reach a particular level of divergence. Here I have explored these two parameters of disparification in bacteria. Owing to low recombination rates, sexual isolation is not a necessary milestone of bacterial speciation. Rather, irreversible and indefinite divergence begins with ecological diversification, that is, transmission of a bacterial lineage to a new ecological niche, possibly to a new microhabitat but at least to new resources. Several algorithms use sequence data from a taxon of focus to identify phylogenetic groups likely to bear the dynamic properties of species. Identifying these newly divergent lineages allows us to characterize the genetic bases of speciation, as well as the ecological dimensions upon which new species diverge. Speciation appears to be least frequent when a given lineage has few new resources it can adopt, as exemplified by photoautotrophs, C1 heterotrophs, and obligately intracellular pathogens; speciation is likely most rapid for generalist heterotrophs. The genetic basis of ecological divergence may determine whether ecological divergence is irreversible and whether lineages will diverge indefinitely into the future. Long-term coexistence is most likely when newly divergent lineages utilize at least some resources not shared with the other and when the resources themselves will coexist into the remote future.

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Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs

Cited by 281 publications

References 45 publications

Evidence and role for bacterial mucin degradation in cystic fibrosis airway disease

Evidence and role for bacterial mucin degradation in cystic fibrosis airway disease

Facultative Control of Matrix Production Optimizes Competitive Fitness in Pseudomonas aeruginosa PA14 Biofilm Models

Transmission in the Origins of Bacterial Diversity, From Ecotypes to Phyla

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