Christopher I Graham, Andrew J Gierys, Teassa L MacMartin, Tiffany V Penner, Jordan C Beck, Gerd Prehna, Teresa R de Kievit, Ann Karen C Brassinga
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引用次数: 0
Abstract
The environmental bacterium Legionella pneumophila, an intracellular parasite of free-living freshwater protozoa as well as an opportunistic human pathogen, has a biphasic lifestyle. The switch from the vegetative replicative form to the environmentally resilient transmissive phase form is governed by a complex stringent response-based regulatory network that includes RNA polymerase co-factor DksA. Here, we report that, through a dysfunctional DksA mutation (DksA1), a synergistic interplay was discovered between DksA and transcription regulator PsrA using the Acanthamoeba castellanii protozoan infection model. Surprisingly, in trans expression of PsrA partially rescued the growth defect of a dksA1 strain. Whilst in trans expression of DksA expectantly could fully rescue the growth defect of the dksA1 strain, it could also surprisingly rescue the growth defect of a ΔpsrA strain. Conversely, the severe intracellular growth defect of a ΔdksA strain could be rescued by in trans expression of DksA and DksA1, but not PsrA. In vitro phenotypic assays show that either DksA or DksA1 was required for extended culturability of bacterial cells, but normal cell morphology and pigmentation required DksA only. Comparative structural modelling predicts that the DksA1 mutation affects the coordination of Mg2+ into the active site of RNAP, compromising transcription efficiency. Taken together, we propose that PsrA transcriptionally assists DksA in the expression of select transmissive phase traits. Additionally, in vitro evidence suggests that the long-chain fatty acid metabolic response is mediated by PsrA together with DksA, inferring a novel regulatory link to the stringent response pathway.
期刊介绍:
We publish high-quality original research on bacteria, fungi, protists, archaea, algae, parasites and other microscopic life forms.
Topics include but are not limited to:
Antimicrobials and antimicrobial resistance
Bacteriology and parasitology
Biochemistry and biophysics
Biofilms and biological systems
Biotechnology and bioremediation
Cell biology and signalling
Chemical biology
Cross-disciplinary work
Ecology and environmental microbiology
Food microbiology
Genetics
Host–microbe interactions
Microbial methods and techniques
Microscopy and imaging
Omics, including genomics, proteomics and metabolomics
Physiology and metabolism
Systems biology and synthetic biology
The microbiome.