Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome

Ecological networking and in vitro studies predict that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes. The metabolic byproducts from these bacteria facilitate the colonization and growth of CF pathogens like <i>Pseudomonas aeruginosa</i>. He...

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Autores principales:	Cynthia B. Silveira, Ana G. Cobián-Güemes, Carla Uranga, Jonathon L. Baker, Anna Edlund, Forest Rohwer, Douglas Conrad
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	clindamycin anaerobes fermentation mucus plugs WinCF metagenomics Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c656425fe5004aa19b30f142bea1753c
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spelling	oai:doaj.org-article:c656425fe5004aa19b30f142bea1753c2021-11-11T17:26:55ZMulti-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome10.3390/ijms2221120501422-00671661-6596https://doaj.org/article/c656425fe5004aa19b30f142bea1753c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12050https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Ecological networking and in vitro studies predict that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes. The metabolic byproducts from these bacteria facilitate the colonization and growth of CF pathogens like <i>Pseudomonas aeruginosa</i>. Here, a multi-omics study informed the control of putative anaerobic keystone species during a transition in antibiotic therapy of a CF patient. A quantitative metagenomics approach combining sequence data with epifluorescence microscopy showed that during periods of rapid lung function loss, the patient’s lung microbiome was dominated by the anaerobic, mucus-degrading bacteria belonging to <i>Streptococcus</i>, <i>Veillonella</i>, and <i>Prevotella</i> genera. Untargeted metabolomics and community cultures identified high rates of fermentation in these sputa, with the accumulation of lactic acid, citric acid, and acetic acid. <i>P. aeruginosa</i> utilized these fermentation products for growth, as indicated by quantitative transcriptomics data. Transcription levels of <i>P. aeruginosa</i> genes for the utilization of fermentation products were proportional to the abundance of anaerobic bacteria. Clindamycin therapy targeting Gram-positive anaerobes rapidly suppressed anaerobic bacteria and the accumulation of fermentation products. Clindamycin also lowered the abundance and transcription of <i>P. aeruginosa,</i> even though this patient’s strain was resistant to this antibiotic. The treatment stabilized the patient’s lung function and improved respiratory health for two months, lengthening by a factor of four the between-hospitalization time for this patient. Killing anaerobes indirectly limited the growth of <i>P. aeruginosa</i> by disrupting the cross-feeding of fermentation products. This case study supports the hypothesis that facultative anaerobes operated as keystone species in this CF microbiome. Personalized multi-omics may become a viable approach for routine clinical diagnostics in the future, providing critical information to inform treatment decisions.Cynthia B. SilveiraAna G. Cobián-GüemesCarla UrangaJonathon L. BakerAnna EdlundForest RohwerDouglas ConradMDPI AGarticleclindamycinanaerobesfermentationmucus plugsWinCFmetagenomicsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12050, p 12050 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	clindamycin anaerobes fermentation mucus plugs WinCF metagenomics Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	clindamycin anaerobes fermentation mucus plugs WinCF metagenomics Biology (General) QH301-705.5 Chemistry QD1-999 Cynthia B. Silveira Ana G. Cobián-Güemes Carla Uranga Jonathon L. Baker Anna Edlund Forest Rohwer Douglas Conrad Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome
description	Ecological networking and in vitro studies predict that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes. The metabolic byproducts from these bacteria facilitate the colonization and growth of CF pathogens like <i>Pseudomonas aeruginosa</i>. Here, a multi-omics study informed the control of putative anaerobic keystone species during a transition in antibiotic therapy of a CF patient. A quantitative metagenomics approach combining sequence data with epifluorescence microscopy showed that during periods of rapid lung function loss, the patient’s lung microbiome was dominated by the anaerobic, mucus-degrading bacteria belonging to <i>Streptococcus</i>, <i>Veillonella</i>, and <i>Prevotella</i> genera. Untargeted metabolomics and community cultures identified high rates of fermentation in these sputa, with the accumulation of lactic acid, citric acid, and acetic acid. <i>P. aeruginosa</i> utilized these fermentation products for growth, as indicated by quantitative transcriptomics data. Transcription levels of <i>P. aeruginosa</i> genes for the utilization of fermentation products were proportional to the abundance of anaerobic bacteria. Clindamycin therapy targeting Gram-positive anaerobes rapidly suppressed anaerobic bacteria and the accumulation of fermentation products. Clindamycin also lowered the abundance and transcription of <i>P. aeruginosa,</i> even though this patient’s strain was resistant to this antibiotic. The treatment stabilized the patient’s lung function and improved respiratory health for two months, lengthening by a factor of four the between-hospitalization time for this patient. Killing anaerobes indirectly limited the growth of <i>P. aeruginosa</i> by disrupting the cross-feeding of fermentation products. This case study supports the hypothesis that facultative anaerobes operated as keystone species in this CF microbiome. Personalized multi-omics may become a viable approach for routine clinical diagnostics in the future, providing critical information to inform treatment decisions.
format	article
author	Cynthia B. Silveira Ana G. Cobián-Güemes Carla Uranga Jonathon L. Baker Anna Edlund Forest Rohwer Douglas Conrad
author_facet	Cynthia B. Silveira Ana G. Cobián-Güemes Carla Uranga Jonathon L. Baker Anna Edlund Forest Rohwer Douglas Conrad
author_sort	Cynthia B. Silveira
title	Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome
title_short	Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome
title_full	Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome
title_fullStr	Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome
title_full_unstemmed	Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome
title_sort	multi-omics study of keystone species in a cystic fibrosis microbiome
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c656425fe5004aa19b30f142bea1753c
work_keys_str_mv	AT cynthiabsilveira multiomicsstudyofkeystonespeciesinacysticfibrosismicrobiome AT anagcobianguemes multiomicsstudyofkeystonespeciesinacysticfibrosismicrobiome AT carlauranga multiomicsstudyofkeystonespeciesinacysticfibrosismicrobiome AT jonathonlbaker multiomicsstudyofkeystonespeciesinacysticfibrosismicrobiome AT annaedlund multiomicsstudyofkeystonespeciesinacysticfibrosismicrobiome AT forestrohwer multiomicsstudyofkeystonespeciesinacysticfibrosismicrobiome AT douglasconrad multiomicsstudyofkeystonespeciesinacysticfibrosismicrobiome
_version_	1718432087480991744

Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome

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