Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance

ABSTRACT Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens that colonize household water systems and cause chronic lung infections in susceptible patients. The ability of NTM to form surface-attached biofilms in the nonhost environment and corded aggregates in vivo is important...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	William H. DePas, Megan Bergkessel, Dianne K. Newman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Mycobacterium biofilms carbon metabolism nitrogen metabolism physiology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b528426a812e4246884ede3ac8e407fb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b528426a812e4246884ede3ac8e407fb
record_format	dspace
spelling	oai:doaj.org-article:b528426a812e4246884ede3ac8e407fb2021-11-15T16:22:11ZAggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance10.1128/mBio.01715-192150-7511https://doaj.org/article/b528426a812e4246884ede3ac8e407fb2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01715-19https://doaj.org/toc/2150-7511ABSTRACT Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens that colonize household water systems and cause chronic lung infections in susceptible patients. The ability of NTM to form surface-attached biofilms in the nonhost environment and corded aggregates in vivo is important to their ability to persist in both contexts. Underlying the development of these multicellular structures is the capacity of mycobacterial cells to adhere to one another. Unlike most other bacteria, NTM spontaneously and constitutively aggregate in vitro, hindering our ability to understand the transition between planktonic and aggregated cells. While culturing a model NTM, Mycobacterium smegmatis, in rich medium, we fortuitously discovered that planktonic cells accumulate after ∼3 days of growth. By providing selective pressure for bacteria that disperse earlier, we isolated a strain with two mutations in the oligopeptide permease operon (opp). A mutant lacking the opp operon (Δopp) disperses earlier than wild type (WT) due to a defect in nutrient uptake. Experiments with WT M. smegmatis revealed that growth as aggregates is favored when carbon is replete, but under conditions of low available carbon relative to available nitrogen, M. smegmatis grows as planktonic cells. By adjusting carbon and nitrogen sources in defined medium, we tuned the cellular C/N ratio such that M. smegmatis grows either as aggregates or as planktonic cells. C/N-mediated aggregation regulation is widespread among NTM with the possible exception of rough-colony Mycobacterium abscessus isolates. Altogether, we show that NTM aggregation is a controlled process that is governed by the relative availability of carbon and nitrogen for metabolism. IMPORTANCE Free-living bacteria can assemble into multicellular structures called biofilms. Biofilms help bacteria tolerate multiple stresses, including antibiotics and the host immune system. Nontuberculous mycobacteria are a group of emerging opportunistic pathogens that utilize biofilms to adhere to household plumbing and showerheads and to avoid phagocytosis by host immune cells. Typically, bacteria regulate biofilm formation by controlling expression of adhesive structures to attach to surfaces and other bacterial cells. Mycobacteria harbor a unique cell wall built chiefly of long-chain mycolic acids that confers hydrophobicity and has been thought to cause constitutive aggregation in liquid media. Here we show that aggregation is instead a regulated process dictated by the balance of available carbon and nitrogen. Understanding that mycobacteria utilize metabolic cues to regulate the transition between planktonic and aggregated cells reveals an inroad to controlling biofilm formation through targeted therapeutics.William H. DePasMegan BergkesselDianne K. NewmanAmerican Society for MicrobiologyarticleMycobacteriumbiofilmscarbon metabolismnitrogen metabolismphysiologyMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterium biofilms carbon metabolism nitrogen metabolism physiology Microbiology QR1-502
spellingShingle	Mycobacterium biofilms carbon metabolism nitrogen metabolism physiology Microbiology QR1-502 William H. DePas Megan Bergkessel Dianne K. Newman Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance
description	ABSTRACT Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens that colonize household water systems and cause chronic lung infections in susceptible patients. The ability of NTM to form surface-attached biofilms in the nonhost environment and corded aggregates in vivo is important to their ability to persist in both contexts. Underlying the development of these multicellular structures is the capacity of mycobacterial cells to adhere to one another. Unlike most other bacteria, NTM spontaneously and constitutively aggregate in vitro, hindering our ability to understand the transition between planktonic and aggregated cells. While culturing a model NTM, Mycobacterium smegmatis, in rich medium, we fortuitously discovered that planktonic cells accumulate after ∼3 days of growth. By providing selective pressure for bacteria that disperse earlier, we isolated a strain with two mutations in the oligopeptide permease operon (opp). A mutant lacking the opp operon (Δopp) disperses earlier than wild type (WT) due to a defect in nutrient uptake. Experiments with WT M. smegmatis revealed that growth as aggregates is favored when carbon is replete, but under conditions of low available carbon relative to available nitrogen, M. smegmatis grows as planktonic cells. By adjusting carbon and nitrogen sources in defined medium, we tuned the cellular C/N ratio such that M. smegmatis grows either as aggregates or as planktonic cells. C/N-mediated aggregation regulation is widespread among NTM with the possible exception of rough-colony Mycobacterium abscessus isolates. Altogether, we show that NTM aggregation is a controlled process that is governed by the relative availability of carbon and nitrogen for metabolism. IMPORTANCE Free-living bacteria can assemble into multicellular structures called biofilms. Biofilms help bacteria tolerate multiple stresses, including antibiotics and the host immune system. Nontuberculous mycobacteria are a group of emerging opportunistic pathogens that utilize biofilms to adhere to household plumbing and showerheads and to avoid phagocytosis by host immune cells. Typically, bacteria regulate biofilm formation by controlling expression of adhesive structures to attach to surfaces and other bacterial cells. Mycobacteria harbor a unique cell wall built chiefly of long-chain mycolic acids that confers hydrophobicity and has been thought to cause constitutive aggregation in liquid media. Here we show that aggregation is instead a regulated process dictated by the balance of available carbon and nitrogen. Understanding that mycobacteria utilize metabolic cues to regulate the transition between planktonic and aggregated cells reveals an inroad to controlling biofilm formation through targeted therapeutics.
format	article
author	William H. DePas Megan Bergkessel Dianne K. Newman
author_facet	William H. DePas Megan Bergkessel Dianne K. Newman
author_sort	William H. DePas
title	Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance
title_short	Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance
title_full	Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance
title_fullStr	Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance
title_full_unstemmed	Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance
title_sort	aggregation of nontuberculous mycobacteria is regulated by carbon-nitrogen balance
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b528426a812e4246884ede3ac8e407fb
work_keys_str_mv	AT williamhdepas aggregationofnontuberculousmycobacteriaisregulatedbycarbonnitrogenbalance AT meganbergkessel aggregationofnontuberculousmycobacteriaisregulatedbycarbonnitrogenbalance AT dianneknewman aggregationofnontuberculousmycobacteriaisregulatedbycarbonnitrogenbalance
_version_	1718426926058569728

Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance

Ejemplares similares