Biofilm Resilience: Molecular Mechanisms Driving Antibiotic Resistance in Clinical Contexts

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 165 - 165

Published: Feb. 6, 2025

Healthcare-associated infections pose a significant global health challenge, negatively impacting patient outcomes and burdening healthcare systems. A major contributing factor to healthcare-associated is the formation of biofilms, structured microbial communities encased in self-produced extracellular polymeric substance matrix. Biofilms are critical disease etiology antibiotic resistance, complicating treatment infection control efforts. Their inherent resistance mechanisms enable them withstand therapies, leading recurrent increased morbidity. This review explores development biofilms their dual roles disease. It highlights structural protective functions EPS matrix, which shields populations from immune responses antimicrobial agents. Key molecular biofilm including restricted penetration, persister cell dormancy, genetic adaptations, identified as barriers effective management. implicated various clinical contexts, chronic wounds, medical device-associated infections, oral complications, surgical site infections. prevalence hospital environments exacerbates challenges underscores urgent need for innovative preventive therapeutic strategies. evaluates cutting-edge approaches such DNase-mediated disruption, RNAIII-inhibiting peptides, DNABII proteins, bacteriophage nanoparticle-based solutions, coatings, lock therapies. also examines associated with biofilm-related diagnostic difficulties, disinfectant economic implications. emphasizes multidisciplinary approach importance understanding dynamics, role pathogenesis, advancements strategies combat biofilm-associated effectively settings. These insights aim enhance reduce burden diseases.

Language: Английский

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Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 7, 2024

Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These are problematic because they frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability bacteria persist despite normally lethal doses antibiotics, contributes treatment failure in S. infections. To understand how tolerance induced, biofilms exposed multiple anti-staphylococcal antibiotics examined using both quantitative proteomics and transposon sequencing. screens indicate that arginine metabolism involved within biofilm support hypothesis depletion communities can induce tolerance. Consistent with this hypothesis, inactivation argH, final gene synthesis pathway, induces Arginine restriction via inhibition protein synthesis. In murine skin bone infection models, an argH mutant has enhanced survive vancomycin, highlighting relationship between during infection. Uncovering link potential open new therapeutic avenues targeting previously Utilising proteomic sequencing screens, Freiberg et al. identified enzymes impact aureus, including animal models

Language: Английский

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Balancing the AspC and AspA Pathways of Escherichia coli by Systematic Metabolic Engineering Strategy for High-Efficient l-Homoserine Production

ACS Synthetic Biology, Journal Year: 2024, Volume and Issue: 13(8), P. 2457 - 2469

Published: July 23, 2024

l-Homoserine is a promising C4 platform compound used in the agricultural, cosmetic, and pharmaceutical industries. Numerous works have been conducted to engineer

Language: Английский

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Metabolic pathways and antimicrobial peptide resistance in bacteria

Journal of Antimicrobial Chemotherapy, Journal Year: 2024, Volume and Issue: 79(7), P. 1473 - 1483

Published: May 14, 2024

Abstract Antimicrobial resistance is a pressing concern that poses significant threat to global public health, necessitating the exploration of alternative strategies combat drug-resistant microbial infections. Recently, antimicrobial peptides (AMPs) have gained substantial attention as possible replacements for conventional antibiotics. Because their pharmacodynamics and killing mechanisms, AMPs display lower risk bacterial evolution compared with most However, bacteria different mechanisms resist AMPs, role metabolic pathways in mechanism not fully understood. This review examines intricate relationship between genes AMP resistance, focusing on impact various aspects resistance. Metabolic related guanosine pentaphosphate (pppGpp) tetraphosphate (ppGpp) [collectively (p)ppGpp], tricarboxylic acid (TCA) cycle, haem biosynthesis, purine pyrimidine amino lipid metabolism influence ways adjustments, biofilm formation energy production could be involved By targeting associated genes, it enhance efficacy existing therapies overcome challenges exhibited by phenotypic (recalcitrance) genetic toward AMPs. Further research this area needed provide valuable insights into specific uncover novel therapeutic targets, aid fight against

Language: Английский

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Bacterial dormancy: strategies and molecular mechanisms for a sleeping beauty system

Reviews in Medical Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Bacterial dormancy is a state of decreased metabolic activity that allows bacteria to survive in harsh environments. reversible shutdown; it nonreplicating cell which enable them under unfavorable conditions. Dormancy facilitated by molecular mechanisms involve signaling pathways, translational and transcriptional regulation, shifts. Persisted cells, are highly tolerant antibiotics, formed during dormancy, posing significant challenge the treatment bacterial infections. Understanding crucial for developing strategies control persistence advance antibiotic discovery. Sporulation purest form microbial dormancy. Spores resistant stresses such as extreme heat, chemicals, radiation, can survive. Dormant blood not growing but dormant microbiome significantly take part large diverse chronic inflammatory diseases. This review discusses importance, mechanisms, entering state, explores physiological changes occur Additionally, sheds light on methods identification investigation may help overcoming drug resistance

Language: Английский

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Light-Based Anti-Biofilm and Antibacterial Strategies

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2106 - 2106

Published: Aug. 9, 2023

Biofilm formation and antimicrobial resistance pose significant challenges not only in clinical settings (i.e., implant-associated infections, endocarditis, urinary tract infections) but also industrial the environment, where spreading of antibiotic-resistant bacteria is on rise. Indeed, developing effective strategies to prevent biofilm treat infections will be one major global next few years. As traditional pharmacological treatments are becoming inadequate curb this problem, a constant commitment exploration novel therapeutic necessary. Light-triggered therapies have emerged as promising alternatives approaches due their non-invasive nature, precise spatial temporal control, potential multifunctional properties. Here, we provide comprehensive overview different stages molecular mechanism disruption, with focus quorum sensing machinery. Moreover, highlight principal guidelines for development light-responsive materials photosensitive compounds. The synergistic effects combining light-triggered conventional discussed. Through elegant material design solutions, remarkable results been achieved fight against antibacterial resistance. However, further research field essential optimize translate them into applications, ultimately addressing posed by

Language: Английский

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(p)ppGpp-mediated GTP homeostasis ensures the survival and antibiotic tolerance ofStaphylococcus aureusduring starvation by preserving the proton motive force

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 6, 2024

Abstract Upon nutrient limitation bacteria enter a nongrowing state, which allow bacterial survival and antibiotic tolerance. The mechanisms whether how the messenger molecule (p)ppGpp contributes to transition in Firmicutes is debated. Here we show for Staphylococcus aureus that (p)ppGpp-dependent restriction of GTP pool essential culturability starved cells Elevated levels starving (p)ppGpp-deficient mutant lead division-incompetent, dormant state characterized by reduced metabolic activity alterations membrane function architecture. level control nucleotide sensitive promoters result transcriptional downregulation gene TCA cycle electron transport chain. Increasing transcription qoxABCD , terminal oxidase respiratory chain, through mutation start site partially restored mutant. Furthermore, showed maintenance proton motive force under nutritional stress tolerance, supporting idea applying or PMF inhibitors combat antibiotic-tolerant bacteria.

Language: Английский

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Potential Risks and Challenges of Bacterial Persistence in Food Safety

Food Reviews International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 20

Published: Jan. 17, 2025

Bacterial persisters are becoming increasingly recognized as an emerging public health concern due to the potential causes of chronic infections in clinical settings and treatment failures food industry. The transiently tolerant antibiotics environmental stresses. Thus, understanding mechanisms underlying persister formation foodborne pathogens is essential for assessing safety risks environments. molecular associated with bacterial tolerance persistence can be new targets controlling antibiotic-resistant pathogens. In addition, reversible phenotypic switch non-heritable characteristics used re-sensitize cells then directly inhibit dormant cells. However, because there has still been insufficient information on persistence, we have faced a significant challenge development effective anti-persister agents. Therefore, aims this review examine significance association antibiotic resistance, discuss concerns cells, provide insight products.

Language: Английский

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(p)ppGpp-mediated GTP homeostasis ensures survival and antibiotic tolerance of Staphylococcus aureus

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 28, 2025

Antibiotic tolerance in non-growing bacterial populations is of major concern regarding antibiotic treatment failures. Whether and how the messenger molecule (p)ppGpp contributes to this phenomenon controversial. We show for Staphylococcus aureus that (p)ppGpp-dependent restriction GTP pool essential culturability starved cells. Survival was independent GTP-responsive regulator CodY. Elevated levels a (p)ppGpp-deficient mutant led quiescent state characterised by alterations membrane architecture decrease proton motive force (PMF). This accompanied dysregulation components involved electron transport, including qoxABCD, encoding main terminal oxidase. Increasing qoxABCD transcription mutation start site (iATP iGTP) partially restored mutant. Thus, regulation nucleotide-dependent promoters altered nucleotide contribute starvation adaptability. Loss PMF under high conditions also renders bacteria susceptible antibiotics. targeting or availability may be valuable strategy combat tolerance.

Language: Английский

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Role of RelA-synthesized (p)ppGpp and ROS-induced mutagenesis in de novo acquisition of antibiotic resistance in E. coli

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109579 - 109579

Published: March 26, 2024

The stringent response of bacteria to starvation and stress also fulfills a role in addressing the threat antibiotics. Within this response, (p)ppGpp, synthesized by RelA or SpoT, functions as global alarmone. However, effect (p)ppGpp on resistance development is poorly understood. Here, we show that knockout

Language: Английский

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