Advancements in function recognition of staphyloxanthin and targeted inhibitor development

Current Opinion in Food Science, Journal Year: 2025, Volume and Issue: unknown, P. 101300 - 101300

Published: March 1, 2025

Language: Английский

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Sub-inhibitory concentrations of tigecycline could attenuate the virulence of Staphylococcus aureus by inhibiting the product of α-toxin

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

ABSTRACT Staphylococcus aureus ( S. ) infection is a serious threat to global health. This study aimed investigate the anti-virulence efficacy of tigecycline against . We used highly virulent strains SA75 and JP30 evaluate effect on virulence, both them isolated from clinic. The MIC value was 0.125 µg/mL, that 0.25 µg/mL. Tigecycline did not affect growth ability bacteria at 0.015 Thus, subsequent discussions will focus antibiotics latter subinhibitory concentrations growth. First, sub-MICs only enhanced sensitivity oxidants human whole blood but also weakened hemolytic activity cell adhesion level Second, it undermined survival in RAW264.7 attenuated macrophage inflammatory response induced by On contrary, decreased activity, as well skin abscess formation bacterial burden mice. Most importantly, significantly expression hla , hlgB hlgC spa sbi saeR sak tst coa genes RT-qPCR protein α-toxin. Altogether, might be promising agent attenuate virulence its host immune inhibiting SaeRS two-component system product IMPORTANCE In this study, resistance blood. Moreover, mice reducing burden. Remarkably, downregulated various research highlighted

Language: Английский

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A natural inhibitor of diapophytoene desaturase attenuates methicillin‐resistant Staphylococcus aureus (MRSA) pathogenicity and overcomes drug‐resistance

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(15), P. 2583 - 2599

Published: April 11, 2024

At present, the inhibition of staphyloxanthin biosynthesis has emerged as a prominent strategy in combating methicillin-resistant Staphylococcus aureus (MRSA) infection. Nonetheless, there remains limited understanding regarding bio-structural characteristics biosynthetic enzymes, well molecular mechanisms underlying interaction between inhibitors and proteins. Furthermore, functional scope these is relatively narrow.

Language: Английский

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Novel anti-virulence compounds disrupt exotoxin expression in MRSA

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

ABSTRACT Hemolysins are lytic exotoxins expressed in most strains of S. aureus , but hemolytic activity varies between strains. We have previously reported several novel anti-virulence compounds that disrupt the transcriptome, including hemolysin gene expression. This report delves further into our two lead compounds, loratadine and a structurally related brominated carbazole, their effects on production methicillin-resistant (MRSA). To gain understanding how these affect hemolysis, we analyzed at DNA, RNA, protein level after vitro treatment. While lysis red blood cells varied strains, DNA sequence variation did not account for it. hypothesized would modulate expression multiple hemolysins hospital-acquired MRSA, both with staphylococcal cassette chromosome mec (SCC ) type II. RNA-seq analysis differential untreated compound-treated cultures revealed hundreds differentially genes, significant enrichment genes involved hemolysis. The carbazole displayed ability to reduce hemolysis strain 43300 USA100. These results corroborate studies as well western blots alpha hemolysin. Together, this work suggests small molecules may alter exotoxin MRSA directionality and/or magnitude difference likely dependent. IMPORTANCE Methicillin-resistant (MRSA) is deadly human pathogen. In addition evading antibiotics, bacteria produce wide range toxins negatively host. Our aims identify characterize can decrease pathogenic MRSA. Two investigated study triggered changes toxins. were specific investigated. Specifically, sheds light MRSA’s lyse host cells. Importantly, it also highlights importance examining strain-specific differences response therapeutic interventions could ultimately clinical outcomes.

Language: Английский

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A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(6)

Published: Oct. 11, 2023

Biofilms are an important virulence factor in Staphylococcus aureus and characterized by a structured microbial community consisting of bacterial cells secreted extracellular polymeric matrix. Inhibition biofilm formation is effective measure to control S. infection. Here, we have synthesized small molecule compound S-342-3, which exhibits potent inhibition both MRSA MSSA. Further investigations revealed that S-342-3 exerts inhibitory effects on reducing the production polysaccharide intercellular adhesin preventing adhesion. Our study has confirmed effect achieved downregulating expression genes responsible for formation. In addition, non-toxic Galleria mellonella larvae A549 cells. Consequently, this demonstrates efficacy biologically safe inhibiting aureus, thereby providing promising antibiofilm agent further research.

Language: Английский

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Novel Antimicrobials, Drug Delivery Systems and Antivirulence Targets in the Pipeline—From Bench to Bedside

Applied Sciences, Journal Year: 2022, Volume and Issue: 12(22), P. 11615 - 11615

Published: Nov. 16, 2022

In a fast-paced medical reality, biosciences and bioengineering have become essential components in research development. The aim of this paper is to characterize the recent progresses made fighting antimicrobial resistance, particularly relation WHO’s priority pathogens, by providing an in-depth review novel antimicrobials, drug delivery systems for targeted action antivirulence targets. We systematically searched ClinicalTrials.gov database identify clinical trials targeting 1 (critical) pathogens: carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, ESBL-producing Enterobacteriaceae. identified limited number trials, specifically for: one betalactamase inhibitor spp., anti-virulence human monoclonal antibody spp. no antimicrobials also performed field literature exemplify main applications infectious diseases, achieving antibiotic distribution, enhancing local activity with reduced off-target effects, triggered release antibacterial photodynamic therapy. conclude presenting targets therapeutics that act disrupting quorum sensing, inhibiting bacterial adherence biofilm formation, silencing virulence traits neutralizing toxins. Furthermore, principles rational use are highlighted, effort describe potential areas intervention, from diagnostic stewardship stewardship.

Language: Английский

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Novel Anti-virulence Compounds Disrupt Exotoxin Expression in MRSA

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

Published: May 15, 2024

Abstract Hemolysins are lytic exotoxins expressed in most strains of S. aureus , but hemolytic activity varies between strains. We have previously reported several novel anti-virulence compounds that disrupt the transcriptome, including hemolysin gene expression. This report delves further into our two lead compounds, loratadine and a structurally related brominated carbazole, their effects on production MRSA. To gain understanding how these affect hemolysis, we analyzed at DNA, RNA, protein level after vitro treatment. While lysis red blood cells varied strains, DNA sequence variation did not account for it. hypothesized would modulate expression multiple hemolysins laboratory strain clinically relevant hospital-acquired MRSA, both with SCC mec type II. RNA-seq analysis differential untreated compound-treated cultures revealed hundreds differentially genes, significant enrichment genes involved hemolysis. The carbazole displayed ability to reduce hemolysis strain, strain. These results corroborate studies as well western blots alpha hemolysin. Together, this work suggests small molecules may alter exotoxin directionality and/or magnitude difference is likely strain-dependent.

Language: Английский

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Emergence of an unconventional Enterobacter cloacae-derived Iturin A C-15 as a potential therapeutic agent against methicillin-resistant Staphylococcus aureus

Archives of Microbiology, Journal Year: 2024, Volume and Issue: 207(1)

Published: Dec. 30, 2024

Language: Английский

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Galleria Mellonella Larvae as an In vitro Model for Testing Microbial Pathogenicity

Postępy Mikrobiologii - Advancements of Microbiology, Journal Year: 2023, Volume and Issue: 62(3-4), P. 173 - 182

Published: Nov. 1, 2023

Abstract The larvae of the insect Galleria mellonella have gained wide acceptance as an in vivo model for study virulence Gram-negative and Gram-positive bacteria fungi. Importantly, G. offers alternative, low-cost, ethically acceptable method assessing pathogens. These insects a number advantages, including ease breeding, rapid developmental cycle, low maintenance costs, experimental manipulation. Most importantly, complete immune system nonspecific response similar to that humans, making them valuable studying pathogen-host interactions. Furthermore, using this model, it is possible test efficacy various chemical compounds or natural substances show antimicrobial activity. In literature review, we provide comprehensive overview recent studies use analyses platform testing new drugs.

Language: Английский

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