Dataset Information

Identification of catabolite control protein A from Staphylococcus aureus as a target of silver ions.

ABSTRACT: Staphylococcus aureus is one of the most common pathogenic bacteria that causes human infectious diseases. The emergence of antibiotic-resistant strains of S. aureus promotes the development of new anti-bacterial strategies. Silver ions (Ag+) have attracted profound attention due to their broad-spectrum antimicrobial activities. Although the antibacterial properties of silver have been well known for many centuries, its mechanism of action remains unclear and its protein targets are rarely reported. Herein, we identify the catabolite control protein A (CcpA) of S. aureus as a putative target for Ag+. CcpA binds 2 molar equivalents of Ag+via its two cysteine residues (Cys216 and Cys242). Importantly, Ag+ binding induces CcpA oligomerization and abolishes its DNA binding capability, which further attenuates S. aureus growth and suppresses ?-hemolysin toxicity. This study extends our understanding of the bactericidal effects of silver.

SUBMITTER: Liao X

PROVIDER: S-EPMC5855135 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of catabolite control protein A from Staphylococcus aureus as a target of silver ions.

Liao Xiangwen X Yang Fang F Wang Runming R He Xiaojun X Li Hongyan H Kao Richard Y T RYT Xia Wei W Sun Hongzhe H

Chemical science 20171002 12

Staphylococcus aureus is one of the most common pathogenic bacteria that causes human infectious diseases. The emergence of antibiotic-resistant strains of S. aureus promotes the development of new anti-bacterial strategies. Silver ions (Ag+) have attracted profound attention due to their broad-spectrum antimicrobial activities. Although the antibacterial properties of silver have been well known for many centuries, its mechanism of action remains unclear and its protein ...[more]

PMID: 29568454

Similar Datasets

Project description:Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kinase, also abrogated growth of JE2 in CDM, suggesting that ATP production from pyruvate-producing amino acids is also critical for growth. In addition, although a functional respiratory chain was absolutely required for growth, the oxygen consumption rate and intracellular ATP concentration were significantly lower during growth in CDM than during growth in glucose-containing media. Finally, transcriptional analyses demonstrated that expression levels of genes coding for the enzymes that synthesize glutamate from proline, arginine, and histidine are repressed by CcpA and carbon catabolite repression. These data show that pathways important for glutamate catabolism or ATP generation via Pta/AckA are important for growth in niches where glucose is not abundant, such as abscesses within skin and soft tissue infections.IMPORTANCES. aureus is a significant cause of both morbidity and mortality worldwide. This bacterium causes infections in a wide variety of organ systems, the most common being skin and soft tissue. Within a staphylococcal abscess, levels of glucose, a preferred carbon source, are limited due to the host immune response. Therefore, S. aureus must utilize other available carbon sources such as amino acids or peptides to proliferate. Our results show that glutamate and amino acids that serve as substrates for glutamate synthesis, particularly proline, function as major carbon sources during growth, whereas other amino acids that generate pyruvate are important for ATP synthesis via substrate-level phosphorylation in the Pta-AckA pathway. Our data support a model whereby certain amino acid catabolic pathways, and acquisition of those particular amino acids, are crucial for growth in niches where glucose is not abundant.

Dataset Information

Identification of catabolite control protein A from Staphylococcus aureus as a target of silver ions.

Publications

Identification of catabolite control protein A from <i>Staphylococcus aureus</i> as a target of silver ions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets