Anaerobic respiration of host-derived methionine sulfoxide protects intracellular Salmonella from the phagocyte NADPH oxidase
Ontology highlight
ABSTRACT: We report the changes in transcriptional landscape that occur under anaerobic conditions in the absence of a DMSO reductase in Salmonella enterica subsp. enterica serovar Typhimurium strain 14028s. By comparing the transcriptome of the parental, wild-type Salmonella to the transcriptome of a ∆dmsABC strain, we identified that there was a significant upregulation of SPI-2 genes in the ∆dmsABC strain.
ORGANISM(S): Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S
Project description:HilD is a regulator of Salmonella pathogenicity island 1 (SPI-1) virulence genes in Salmonella enterica serovar Typhimurium. To identify novel HilD-regulated genes, we mapped the genome-wide association of HilD in S. Typhimurium under SPI-1-inducing conditions (high salt, low aeration) using ChIP-seq. HilD was C-terminally tagged with 3 FLAG tags in strain 14028s.
Project description:Intracellular Salmonella experiencing oxidative stress downregulates aerobic respiration. To maintain cellular energetics during periods of oxidative stress, intracellular Salmonella must utilize terminal electron acceptors of lower energetic value than molecular oxygen. We show here that intracellular Salmonella undergoes anaerobic respiration during adaptation to the respiratory burst of the phagocyte NADPH oxidase in macrophages and in mice. Reactive oxygen species generated by phagocytes oxidize methionine, generating methionine sulfoxide. Anaerobic Salmonella uses the molybdenum cofactor-containing DmsABC enzymatic complex to reduce methionine sulfoxide. The enzymatic activity of the methionine sulfoxide reductase DmsABC helps Salmonella maintain an alkaline cytoplasm that supports the synthesis of the antioxidant hydrogen sulfide via cysteine desulfuration while providing a source of methionine and fostering redox balancing by associated dehydrogenases. Our investigations demonstrate that nontyphoidal Salmonella responding to oxidative stress exploits the anaerobic metabolism associated with dmsABC gene products, a pathway that has accrued inactivating mutations in human-adapted typhoidal serovars.
Project description:We report the findings of genes under the transcriptional control of Gre factors by comparing RNA-seq data from parental, wild-type Salmonella enterica enterica Typhimurium 14028s and a ∆greA ∆greB strain. By comparing differential gene expression, we identify a metabolic scheme for responding to oxidative stress that is regulated in part by the action of Gre factors
Project description:Summary: Salmonella enterica serovar Typhimurium strain 14028s transcriptome response to lettuce medium (LM) and lettuce root exudates (LX) to minimal medium (MM). Purpose: Salmonella mRNA profile, when grown in different media was compared to minimal medium to reveal environment specific transcriptional changes. Methods: mRNA profiles were generated using Illumina HiSeq in triplicates. The sequences were analysed using Bowtie2 followed by Cufflinks.
Project description:Summary: Salmonella enterica serovar Typhimurium strain 14028s transcriptome response to tomato medium (TM) and tomato root exudates (TX) compared to minimal medium (MM). Purpose: Salmonella mRNA profile, when grown in different media was compared to minimal medium to reveal environment specific transcriptional changes. Methods: mRNA profiles were generated using Illumina HiSeq in triplicates. The sequences were analysed using Bowtie2 followed by Cufflinks.
Project description:PacBio SMRT-seq of wild-type, ∆metJ, and ∆dam Salmonella enterica serovar Typhimurium grown under SPI-1-inducing and SPI-2-inducing conditions.