Dataset Information

Acetylation Regulates Survival of Salmonella enterica Serovar Typhimurium under Acid Stress.

ABSTRACT: The ability to acetylate lysine residues is conserved across organisms, and acetylation of lysine residues plays important roles in various cellular functions. Maintaining intracellular pH homeostasis is crucial for the survival of enteric bacteria in the acidic gastric tract. It has been shown that eukaryotes can stabilize the intracellular pH by histone deacetylation. However, it remains unknown whether bacteria can utilize a reversible protein acetylation system to adapt to an acidic environment. Here we demonstrate that protein acetylation/deacetylation is critical for Salmonella enterica serovar Typhimurium to survive in an acidic environment. We used RNA sequencing to analyze the transcriptome patterns under acid stress and found that the transcriptional levels of genes involved in NAD(+)/NADH metabolism were significantly changed, leading to an increase in the intracellular NAD(+)/NADH ratio. Moreover, acid stress downregulated the transcriptional level of pat, encoding acetyltransferase, and genes cyaA and crp, encoding adenylate cyclase and cyclic AMP receptor protein, respectively, which are positive regulators of pat. It was found that the acid signal alerts the tricarboxylic acid cycle to promote the consumption of acetyl coenzyme A (Ac-CoA), an acetyl group donor for the acetylation reaction. A lowered acetylation level not only was the bacterial response to acid stress but also increased the survival rate of S. Typhimurium under acid stress. The pat deletion mutant had a more stable intracellular pH, which paralleled the higher survival rate after acid treatment compared with that of both the wild-type strain and the cobB (encoding deacetylase) deletion mutant. Our data indicate that bacteria can downregulate the protein acetylation level to prevent the intracellular pH from further falling under acid stress, and this work may provide a new perspective to understand the bacterial acid resistance mechanism.

SUBMITTER: Ren J

PROVIDER: S-EPMC4551269 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Acetylation Regulates Survival of Salmonella enterica Serovar Typhimurium under Acid Stress.

Ren Jie J Sang Yu Y Ni Jinjing J Tao Jing J Lu Jie J Zhao Mingwen M Yao Yu-Feng YF

Applied and environmental microbiology 20150612 17

The ability to acetylate lysine residues is conserved across organisms, and acetylation of lysine residues plays important roles in various cellular functions. Maintaining intracellular pH homeostasis is crucial for the survival of enteric bacteria in the acidic gastric tract. It has been shown that eukaryotes can stabilize the intracellular pH by histone deacetylation. However, it remains unknown whether bacteria can utilize a reversible protein acetylation system to adapt to an acidic environm ...[more]

PMID: 26070677

Similar Datasets

Project description:Microbial horizontal gene transfer is a continuous process that shapes bacterial genomic adaptation to the environment and the composition of concurrent microbial ecology. This includes the potential impact of synthetic antibiotic utilization in farm animal production on overall antibiotic resistance issues; however, the mechanisms behind the evolution of microbial communities are not fully understood. We explored potential mechanisms by experimentally examining the relatedness of phylogenetic inference between multidrug-resistant Salmonella enterica serovar Typhimurium isolates and pathogenic Salmonella Typhimurium strains based on genome-wide single-nucleotide polymorphism (SNP) comparisons. Antibiotic-resistant S Typhimurium isolates in a simulated farm environment barely lost their resistance, whereas sensitive S Typhimurium isolates in soils gradually acquired higher tetracycline resistance under antibiotic pressure and manipulated differential expression of antibiotic-resistant genes. The expeditious development of antibiotic resistance and the ensuing genetic alterations in antimicrobial resistance genes in S Typhimurium warrant effective actions to control the dissemination of Salmonella antibiotic resistance.IMPORTANCE Antibiotic resistance is attributed to the misuse or overuse of antibiotics in agriculture, and antibiotic resistance genes can also be transferred to bacteria under environmental stress. In this study, we report a unidirectional alteration in antibiotic resistance from susceptibility to increased resistance. Highly sensitive Salmonella enterica serovar Typhimurium isolates from organic farm systems quickly acquired tetracycline resistance under antibiotic pressure in simulated farm soil environments within 2 weeks, with expression of antibiotic resistance-related genes that was significantly upregulated. Conversely, originally resistant S Typhimurium isolates from conventional farm systems lost little of their resistance when transferred to environments without antibiotic pressure. Additionally, multidrug-resistant S Typhimurium isolates genetically shared relevancy with pathogenic S Typhimurium isolates, whereas susceptible isolates clustered with nonpathogenic strains. These results provide detailed discussion and explanation about the genetic alterations and simultaneous acquisition of antibiotic resistance in S Typhimurium in agricultural environments.

Project description:The Salmonella type three secretion system (T3SS), encoded in the Salmonella pathogenicity island 1 (SPI1) locus, mediates the invasion of the host intestinal epithelium. SPI1 expression is dependent upon three AraC-like regulators: HilD, HilC, and RtsA. These regulators act in a complex feed-forward loop to activate each other and hilA, which encodes the activator of the T3SS structural genes. HilD has been shown to be the major integration point of most signals known to activate the expression of the SPI1 T3SS, acting as a switch to control induction of the system. HilE is a negative regulator that acts upon HilD. Here we provide genetic and biochemical data showing that HilE specifically binds to HilD but not to HilC or RtsA. This protein-protein interaction blocks the ability of HilD to bind DNA as shown by both an in vivo reporter system and an in vitro gel shift assay. HilE does not affect HilD dimerization, nor does it control the stability of the HilD protein. We also investigated the role of HilE during the infection of mice using competition assays. Although deletion of hilE does not confer a phenotype, the hilE mutation does suppress the invasion defect conferred by loss of FliZ, which acts as a positive signal controlling HilD protein activity. Together, these data suggest that HilE functions to restrict low-level HilD activity, preventing premature activation of SPI1 until positive inputs reach a threshold required to fully induce the system.IMPORTANCESalmonella is a leading cause of gastrointestinal and systemic disease throughout the world. The SPI1 T3SS is required for Salmonella to induce inflammatory diarrhea and to gain access to underlying tissue. A complex regulatory network controls expression of SPI1 in response to numerous physiological inputs. Most of these signals impinge primarily on HilD translation or activity. The system is triggered when HilD activity crosses a threshold that allows efficient activation of its own promoter. This threshold is set by HilE, which binds to HilD to prevent the inevitable minor fluctuations in HilD activity from inappropriately activating the system. The circuit also serves as a paradigm for systems that must integrate numerous environmental parameters to control regulatory output.

Dataset Information

Acetylation Regulates Survival of Salmonella enterica Serovar Typhimurium under Acid Stress.

Publications

Acetylation Regulates Survival of Salmonella enterica Serovar Typhimurium under Acid Stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets