Functional and structural characterization of Staphylococcus aureus N‐acetylglucosamine 1‐phosphate uridyltransferase (GlmU) reveals a redox‐sensitive acetyltransferase activity

Protein Science, Journal Year: 2025, Volume and Issue: 34(4)

Published: March 27, 2025

The bifunctional enzyme N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) is a promising antibiotic drug target, as it facilitates the biosynthesis of uridine 5'-diphospho-N-acetylglucosamine, an essential precursor cell wall constituents. We identified that Staphylococcus aureus GlmU (SaGlmU), which was previously targeted for inhibitor development, possesses dual-cysteine variation (C379/C404) within acetyltransferase active site. Enzyme assays performed under reducing and non-reducing conditions revealed activity SaGlmU redox-sensitive, displaying ~15-fold lower turnover ~3-fold higher KM value acetyl CoA substrate conditions. This sensitivity absent in C379A mutant. Analysis by mass spectrometry, x-ray crystallography, silico modeling support C379 C404 act reversible, redox-sensitive switch forming disulfide impedes recognition turnover. Therefore, we recommend future vitro screening characterization inhibitors consider both

Language: Английский

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The Intersection between Bacterial Metabolism and Innate Immunity

Journal of Innate Immunity, Journal Year: 2023, Volume and Issue: 15(1), P. 782 - 803

Published: Jan. 1, 2023

<b><i>Background:</i></b> The innate immune system is the first line of defense against microbial pathogens and essential for maintaining good health. If breach barriers, likelihood infection significantly increased. Many bacterial pose a threat to human health on account their ability evade immunity survive in growth-restricted environments. These have evolved sophisticated strategies obtain nutrients as well manipulate responses, resulting disease or chronic infection. <b><i>Summary:</i></b> relationship between metabolism complex. Although aspects can be beneficial host, particularly those related microbiota barrier integrity, others harmful. Several harness responses persist during study these adaptive traits provides insight into roles pathogenesis that extend beyond energy balance. This review considers recent studies metabolic pathways promote by circumventing several facets system. We also discuss relationships antibiotics highlight future directions research this field. <b><i>Key Messages:</i></b> Pathogenic bacteria remarkable capacity pathogenesis. While we are beginning understand multifaceted complex adaptations occur infection, there still much uncover with research.

Language: Английский

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Subpopulations in Strains of Staphylococcus aureus Provide Antibiotic Tolerance

Antibiotics, Journal Year: 2023, Volume and Issue: 12(2), P. 406 - 406

Published: Feb. 17, 2023

The ability of Staphylococcus aureus to colonise different niches across the human body is linked an adaptable metabolic capability, as well its persist within specific tissues despite adverse conditions. In many cases, S. proliferates anatomical niche, there associated pathology. immune response, together with medical interventions such antibiotics, often removes cells that are causing this disease. However, a common issue in infections relapse Within infected tissue, exists population cells, and it adopts diversity cell types. evolutionary biology, concept “bet-hedging” has established even positive conditions, members arise would be present non-beneficial, but if those conditions change, these traits could allow survival. For aureus, some infection have reduced fitness, not rapidly proliferating or cause active host response disease, do remain after disease seems been cleared. This true for persistence against responses also continual presence spite antibiotic treatment. We propose constant arousal suboptimal populations at any timepoint key strategy long-term Thus, understanding molecular basis feature instrumental combat persistent infections.

Language: Английский

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(P)ppGpp synthetase Rsh participates in rifampicin tolerance of persister cells in Brucella abortus in vitro

Microbial Pathogenesis, Journal Year: 2023, Volume and Issue: 183, P. 106310 - 106310

Published: Aug. 19, 2023

Language: Английский

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Unravelling staphylococcal small-colony variants in cardiac implantable electronic device infections: clinical characteristics, management, and genomic insights

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 8, 2024

Staphylococcal small-colony variants (SCVs) are common in cardiac implantable electronic device (CIED) infections. This is the first retrospective and multi-case study on CIED infections due to staphylococcal SCVs, aiming provide a theoretical basis for clinical management of device-related caused by SCVs.

Language: Английский

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