Defining a temporal order of genetic requirements for development of mycobacterial biofilms

Yong Yang, Joseph Thomas, Yunlong Li, Catherine Vilchèze, Keith M. Derbyshire, William R. Jacobs, Anil K. Ojha

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Most mycobacterial species spontaneously form biofilms, inducing unique growth physiologies and reducing drug sensitivity. Biofilm growth progresses through three genetically programmed stages: substratum attachment, intercellular aggregation and architecture maturation. Growth of Mycobacterium smegmatis biofilms requires multiple factors including a chaperonin (GroEL1) and a nucleoid-associated protein (Lsr2), although how their activities are linked remains unclear. Here it is shown that Lsr2 participates in intercellular aggregation, but substratum attachment of Lsr2 mutants is unaffected, thereby genetically distinguishing these developmental stages. Further, a suppressor mutation in a glycopeptidolipid synthesis gene (mps) that results in hyperaggregation of cells and fully restores the form and functions of Δlsr2 mutant biofilms was identified. Suppression by the mps mutation is specific to Δlsr2; it does not rescue the maturation-deficient biofilms of a ΔgroEL1 mutant, thereby differentiating the process of aggregation from maturation. Gene expression analysis supports a stepwise process of maturation, highlighted by temporally separated, transient inductions of iron and nitrogen import genes. Furthermore, GroEL1 activity is required for induction of nitrogen, but not iron, import genes. Together, the findings begin to define molecular checkpoints during development of mycobacterial biofilms.

Original languageEnglish (US)
Pages (from-to)794-809
Number of pages16
JournalMolecular Microbiology
Volume105
Issue number5
DOIs
StatePublished - Sep 2017

Fingerprint

Biofilms
Nitrogen
Iron
Growth
Chaperonins
Genetic Suppression
Genes
Mycobacterium smegmatis
Gene Expression
Mutation
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Defining a temporal order of genetic requirements for development of mycobacterial biofilms. / Yang, Yong; Thomas, Joseph; Li, Yunlong; Vilchèze, Catherine; Derbyshire, Keith M.; Jacobs, William R.; Ojha, Anil K.

In: Molecular Microbiology, Vol. 105, No. 5, 09.2017, p. 794-809.

Research output: Contribution to journalArticle

Yang, Yong ; Thomas, Joseph ; Li, Yunlong ; Vilchèze, Catherine ; Derbyshire, Keith M. ; Jacobs, William R. ; Ojha, Anil K. / Defining a temporal order of genetic requirements for development of mycobacterial biofilms. In: Molecular Microbiology. 2017 ; Vol. 105, No. 5. pp. 794-809.
@article{b385cd1585b641faa1c4c4782fcb3fb5,
title = "Defining a temporal order of genetic requirements for development of mycobacterial biofilms",
abstract = "Most mycobacterial species spontaneously form biofilms, inducing unique growth physiologies and reducing drug sensitivity. Biofilm growth progresses through three genetically programmed stages: substratum attachment, intercellular aggregation and architecture maturation. Growth of Mycobacterium smegmatis biofilms requires multiple factors including a chaperonin (GroEL1) and a nucleoid-associated protein (Lsr2), although how their activities are linked remains unclear. Here it is shown that Lsr2 participates in intercellular aggregation, but substratum attachment of Lsr2 mutants is unaffected, thereby genetically distinguishing these developmental stages. Further, a suppressor mutation in a glycopeptidolipid synthesis gene (mps) that results in hyperaggregation of cells and fully restores the form and functions of Δlsr2 mutant biofilms was identified. Suppression by the mps mutation is specific to Δlsr2; it does not rescue the maturation-deficient biofilms of a ΔgroEL1 mutant, thereby differentiating the process of aggregation from maturation. Gene expression analysis supports a stepwise process of maturation, highlighted by temporally separated, transient inductions of iron and nitrogen import genes. Furthermore, GroEL1 activity is required for induction of nitrogen, but not iron, import genes. Together, the findings begin to define molecular checkpoints during development of mycobacterial biofilms.",
author = "Yong Yang and Joseph Thomas and Yunlong Li and Catherine Vilch{\`e}ze and Derbyshire, {Keith M.} and Jacobs, {William R.} and Ojha, {Anil K.}",
year = "2017",
month = "9",
doi = "10.1111/mmi.13734",
language = "English (US)",
volume = "105",
pages = "794--809",
journal = "Molecular Microbiology",
issn = "0950-382X",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Defining a temporal order of genetic requirements for development of mycobacterial biofilms

AU - Yang, Yong

AU - Thomas, Joseph

AU - Li, Yunlong

AU - Vilchèze, Catherine

AU - Derbyshire, Keith M.

AU - Jacobs, William R.

AU - Ojha, Anil K.

PY - 2017/9

Y1 - 2017/9

N2 - Most mycobacterial species spontaneously form biofilms, inducing unique growth physiologies and reducing drug sensitivity. Biofilm growth progresses through three genetically programmed stages: substratum attachment, intercellular aggregation and architecture maturation. Growth of Mycobacterium smegmatis biofilms requires multiple factors including a chaperonin (GroEL1) and a nucleoid-associated protein (Lsr2), although how their activities are linked remains unclear. Here it is shown that Lsr2 participates in intercellular aggregation, but substratum attachment of Lsr2 mutants is unaffected, thereby genetically distinguishing these developmental stages. Further, a suppressor mutation in a glycopeptidolipid synthesis gene (mps) that results in hyperaggregation of cells and fully restores the form and functions of Δlsr2 mutant biofilms was identified. Suppression by the mps mutation is specific to Δlsr2; it does not rescue the maturation-deficient biofilms of a ΔgroEL1 mutant, thereby differentiating the process of aggregation from maturation. Gene expression analysis supports a stepwise process of maturation, highlighted by temporally separated, transient inductions of iron and nitrogen import genes. Furthermore, GroEL1 activity is required for induction of nitrogen, but not iron, import genes. Together, the findings begin to define molecular checkpoints during development of mycobacterial biofilms.

AB - Most mycobacterial species spontaneously form biofilms, inducing unique growth physiologies and reducing drug sensitivity. Biofilm growth progresses through three genetically programmed stages: substratum attachment, intercellular aggregation and architecture maturation. Growth of Mycobacterium smegmatis biofilms requires multiple factors including a chaperonin (GroEL1) and a nucleoid-associated protein (Lsr2), although how their activities are linked remains unclear. Here it is shown that Lsr2 participates in intercellular aggregation, but substratum attachment of Lsr2 mutants is unaffected, thereby genetically distinguishing these developmental stages. Further, a suppressor mutation in a glycopeptidolipid synthesis gene (mps) that results in hyperaggregation of cells and fully restores the form and functions of Δlsr2 mutant biofilms was identified. Suppression by the mps mutation is specific to Δlsr2; it does not rescue the maturation-deficient biofilms of a ΔgroEL1 mutant, thereby differentiating the process of aggregation from maturation. Gene expression analysis supports a stepwise process of maturation, highlighted by temporally separated, transient inductions of iron and nitrogen import genes. Furthermore, GroEL1 activity is required for induction of nitrogen, but not iron, import genes. Together, the findings begin to define molecular checkpoints during development of mycobacterial biofilms.

UR - http://www.scopus.com/inward/record.url?scp=85021949275&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021949275&partnerID=8YFLogxK

U2 - 10.1111/mmi.13734

DO - 10.1111/mmi.13734

M3 - Article

C2 - 28628249

AN - SCOPUS:85021949275

VL - 105

SP - 794

EP - 809

JO - Molecular Microbiology

JF - Molecular Microbiology

SN - 0950-382X

IS - 5

ER -