Defining a temporal order of genetic requirements for development of mycobacterial biofilms.
Yong YangJoseph ThomasYunlong LiCatherine VilchèzeKeith M DerbyshireWilliam R JacobsAnil K OjhaPublished in: Molecular microbiology (2017)
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.
Keyphrases
- candida albicans
- genome wide
- mycobacterium tuberculosis
- genome wide identification
- copy number
- wild type
- induced apoptosis
- dna methylation
- staphylococcus aureus
- magnetic resonance
- cell death
- magnetic resonance imaging
- emergency department
- computed tomography
- oxidative stress
- cell cycle arrest
- cell proliferation
- gene expression
- endoplasmic reticulum stress
- signaling pathway
- bioinformatics analysis
- iron deficiency