Dataset Information

Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion

ABSTRACT: The long external filament of bacterial flagella is composed of several thousand copies of a single protein, flagellin. Here, we explore the role played by lysine methylation of flagellin in Salmonella, which requires the methylase FliB. We show that both flagellins of Salmonella enterica serovar Typhimurium, FliC and FljB, are methylated at surface-exposed lysine residues by FliB. A Salmonella Typhimurium mutant deficient in flagellin methylation is outcompeted for gut colonization in a gastroenteritis mouse model, and methylation of flagellin promotes bacterial invasion of epithelial cells in vitro. Lysine methylation increases the surface hydrophobicity of flagellin and enhances flagella-dependent adhesion of Salmonella to phosphatidylcholine vesicles and epithelial cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Salmonella Enterica Subsp. Enterica Serovar Typhimurium Str. Sl1344

SUBMITTER: Christoph Krisp

LAB HEAD: Marc Erhardt

PROVIDER: PXD017935 | Pride | 2020-04-27

REPOSITORIES: pride

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Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion.

Horstmann Julia A JA Lunelli Michele M Cazzola Hélène H Heidemann Johannes J Kühne Caroline C Steffen Pascal P Szefs Sandra S Rossi Claire C Lokareddy Ravi K RK Wang Chu C Lemaire Laurine L Hughes Kelly T KT Uetrecht Charlotte C Schlüter Hartmut H Grassl Guntram A GA Stradal Theresia E B TEB Rossez Yannick Y Kolbe Michael M Erhardt Marc M

Nature communications 20200424 1

The long external filament of bacterial flagella is composed of several thousand copies of a single protein, flagellin. Here, we explore the role played by lysine methylation of flagellin in Salmonella, which requires the methylase FliB. We show that both flagellins of Salmonella enterica serovar Typhimurium, FliC and FljB, are methylated at surface-exposed lysine residues by FliB. A Salmonella Typhimurium mutant deficient in flagellin methylation is outcompeted for gut colonization in a gastroe ...[more]

PMID: 32332720

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Project description:Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative pathogen that must successfully adapt to the broad fluctuations in the concentration of dissolved dioxygen encountered in the host. In Escherichia coli, ArcA (Aerobic Respiratory Control) helps the cells to sense and respond to the presence of dioxygen. The global role of ArcA in E. coli is well characterized; however, little is known about its role in anaerobically grown S. Typhimurium. Results: We compared the transcriptional profiles of the virulent wild-type (WT) strain (ATCC 14028s) and its isogenic arcA mutant grown under anaerobic conditions. We found that ArcA directly or indirectly regulates 392 genes (8.5% of the genome); of these, 138 genes are poorly characterized. Regulation by ArcA in S. Typhimurium is similar, but distinct from that in E. coli. Thus, genes/operons involved in core metabolic pathways (e.g., succinyl-CoA, fatty acid degradation, cytochrome oxidase complexes, flagellar biosynthesis, motility, and chemotaxis) were regulated similarly in the two organisms. However, genes/operons present in both organisms, but regulated differently by ArcA in S. Typhimurium included those coding for ethanolamine utilization, lactate transport and metabolism, and succinate dehydrogenases. Salmonella-specific genes/operons regulated by ArcA included those required for propanediol utilization, flagellar genes (mcpAC, cheV), Gifsy-1 prophage genes, and a few SPI-3 genes (mgtBC, slsA, STM3784). In agreement with our microarray data, the arcA mutant was non-motile, lacked flagella, and was as virulent in mice as the WT. Furthermore, we identified a set of 120 genes whose regulation was shared with the anaerobic redox regulator, Fnr. Conclusion(s): We have identified the ArcA regulon in anaerobically grown S. Typhimurium. Our results demonstrated that in S. Typhimurium, ArcA serves as a transcriptional regulator coordinating cellular metabolism, flagella biosynthesis, and motility. Furthermore, ArcA and Fnr share in the regulation of 120 S. Typhimurium genes.

			Action	DRS
	160712_PS_FliB1.raw	Raw
	160712_PS_FliB2.raw	Raw
	160712_PS_FliB3.raw	Raw
	160712_PS_FliB_delta1.raw	Raw
	160712_PS_FliB_delta2.raw	Raw