Biomedicines, Год журнала: 2023, Номер 11(12), С. 3161 - 3161
Опубликована: Ноя. 28, 2023
The development of bacterial resistance is an increasing global concern that requires discovering new antibacterial agents and strategies. Bacterial quorum sensing (QS) systems play important roles in controlling virulence, their targeting could lead to diminishing pathogenesis. In this context, QS without significant influence on growth assumed as a promising strategy overcome development. This study aimed at evaluating the anti-QS anti-virulence activities β-adrenoreceptor antagonist propranolol sub-minimal inhibitory concentrations (sub-MIC) against two Gram-negative models Pseudomonas aeruginosa Serratia marcescens. effect expression QS-encoding genes was evaluated. Additionally, affinity receptors virtually attested. sub-MIC biofilm formation, motility, production virulent factors conducted. outcomes combination with different antibiotics were assessed. Finally, vivo protection assay mice performed assess propranolol’s lessening current findings emphasized ability reduce formation biofilms, virulence factors. addition, decreased capacity tested bacteria induce pathogenesis mice. Furthermore, significantly downregulated showed receptors. synergistically MICs bacteria. conclusion, might serve plausible adjuvant therapy for treatment serious infections after further pharmacological pharmaceutical studies.
Язык: Английский
Процитировано
16Journal of Ethnopharmacology, Год журнала: 2023, Номер 323, С. 117611 - 117611
Опубликована: Дек. 27, 2023
Язык: Английский
Процитировано
16Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Март 12, 2024
The development of resistance to carbapenems in Klebsiella pneumoniae due the production metallo-β-lactamases (MBLs) is a critical public health problem because are last-resort drugs used for treating severe infections extended-spectrum β-lactamases (ESBLs) producing K. . Restoring activity by inhibition valuable approach combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant isolates were used. sub-inhibitory concentrations pantoprazole well-reported metallo-β-lactamase inhibitor captopril inhibited hydrolytic activities metallo-β-lactamases, with having more inhibiting activities. Both drugs, when combination meropenem, exhibited synergistic Pantoprazole could also downregulate expression genes bla NDM VIM A docking study revealed that bind chelate zinc ions New Delhi Verona integron-encoded MBL (VIM) enzymes higher affinity than control drug comparable natural ligand indicating significant inhibitory against metallo-β-lactamases. conclusion, can be meropenem as new strategy serious caused
Язык: Английский
Процитировано
7Health Sciences Review, Год журнала: 2024, Номер 11, С. 100155 - 100155
Опубликована: Март 11, 2024
Globally, antimicrobial (AMR) or multi-drug resistance (MDR) constitutes a current health challenge that is predicted to cause increased infections rates with adverse socioeconomic impacts through increase in healthcare costs. In addition, the group of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. (ESKAPE) pathogens debilitating (community nosocomial) are classed as priority 1 AMR pathogens. This systematic report therefore aimed at providing detailed coverage new targets for novel antimicrobials development against MDR ESKAPE mitigate future spread improve public indices. The prevalent bacterial show high quinolones, lactams, cephalosporins, carbapenems other antibiotic groups, ability form biofilms linked various quorum sensing systems (QSSs) boost their virulence. These QS pathways have become viable drug design efforts development. Also, since antibiotics discovery has waned past decade, emergence advanced computational modelling technologies design, repurposing may yet bridge gap. As such, this work we provided comprehensive overview using relevant, included data findings on pathogens, QSSs target agents' development, contributions tools heart advancements roles bioprospecting developing 'druggable' candidates therapies anti-biofilm, anti-quorum activities AMR, biofilm QS-related pathogenicity factors.
Язык: Английский
Процитировано
6Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14
Опубликована: Апрель 4, 2024
Pseudomonas aeruginosa belongs to the critical pathogens that represent a global public health problem due their high rate of resistance as listed by WHO. P. can result in many nosocomial infections especially individuals with compromised immune systems. Attenuating virulence factors interference quorum sensing (QS) systems is promising approach treat -resistant infections. Thymoquinone natural compound isolated from Nigella sativa (black seed) essential oil. In this study, minimum inhibitory concentration thymoquinone was detected followed investigating antibiofilm and antivirulence activities subinhibitory against PAO1. The effect on expression QS genes assessed quantitative real-time PCR, protective pathogenesis PAO1 mice mouse survival test. significantly inhibited biofilm, pyocyanin, protease activity, swarming motility. At molecular level, markedly downregulated lasI , l asR rhlI rhlR . Moreover, could protect pathologic effects increasing 20% 100%. conclusion, agent be used an adjunct therapeutic antibiotics attenuate pathogenicity
Язык: Английский
Процитировано
6International Microbiology, Год журнала: 2024, Номер unknown
Опубликована: Май 20, 2024
Язык: Английский
Процитировано
6Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Май 21, 2024
Background P. aeruginosa , a significant bacterium, can cause severe illness and resistance to antibiotics. Quorum sensing (QS) systems regulate virulence factors production. Targeting QS could reduce bacteria pathogenicity prevent antibiotic resistance. Cruciferous vegetables contain sulforaphane, known for its anti-inflammatory, antioxidant, anticancer, antimicrobial properties. Aim We aimed examine the inhibitory influences of at sub-inhibitory concentration (¼ minimum concentration, MIC), on in . Materials methods The sulforaphane’s anti-virulence actions concentrations were explored vitro vivo A sub-MIC sulforaphane was combined with anti-pseudomonal drugs, results this combination assessed. virtual affinity receptors studied, effect expression genes quantified. Results Sulforaphane significantly decreased biofilm formation, motility, ability withstand oxidative stress, synthesis extracellular enzymes such as proteases, hemolysins, elastase, well other like pyocyanin. In addition, lessened severity infection mice. reduced antipseudomonal antibiotics’ MICs when used together, resulting synergistic effects. observed impacts attributed inhibit via suppressing genes’ expression. Conclusion shows promise potent anti-QS agent that be alongside conventional antimicrobials manage infections effectively. Furthermore, study paves way further investigation similar structures pharmacophores candidates.
Язык: Английский
Процитировано
6Antibiotics, Год журнала: 2022, Номер 11(11), С. 1585 - 1585
Опубликована: Ноя. 9, 2022
Salmonella enterica is a Gram-negative orofecal transmitted pathogen that causes wide diversity of local and systemic illnesses. utilizes several interplayed systems to regulate its invasion pathogenesis: namely, quorum sensing (QS) type three secretion system (T3SS). In addition, S. could sense the adrenergic hormones in surroundings enhance virulence. The current study aimed evaluate ability α-adrenoreceptor antagonist prazosin mitigate virulence serovar Typhimurium. effect on biofilm formation expression sdiA, qseC, qseE, T3SS-type II encoding genes was evaluated. Furthermore, intracellular replication inside macrophage anti-virulence activity evaluated vivo against typhimurium. finding showed marked compete SdiA QseC downregulate their genes. Prazosin significantly downregulated factors diminished formation, macrophages, protected mice. To sum up, significant inhibitory activities QS, T3SS, bacterial espionage, which documents considered activities.
Язык: Английский
Процитировано
25Microorganisms, Год журнала: 2023, Номер 11(10), С. 2420 - 2420
Опубликована: Сен. 28, 2023
The problem of antibiotic resistance is a global critical public health concern. In light the threat returning to pre-antibiotic era, new alternative approaches are required such as quorum-sensing (QS) disruption and virulence inhibition, both which apply no discernible selective pressure on bacteria, therefore mitigating potential for development resistant strains. Bearing in mind significant role QS orchestrating bacterial virulence, disrupting becomes essential effectively diminishing virulence. This study aimed assess use sub-inhibitory concentration (0.25 mg/mL) glyceryl trinitrate (GTN) inhibit Serratia marcescens Pseudomonas aeruginosa. GTN could decrease expression genes tested bacteria manner. Histopathological revealed ability alleviate congestion hepatic renal tissues infected mice reduce leukocyte infiltration. recommends topical treat infection caused by P. aeruginosa S. combination with antibiotics.
Язык: Английский
Процитировано
15Pathogens, Год журнала: 2023, Номер 12(5), С. 746 - 746
Опубликована: Май 22, 2023
The current antibiotic crisis and the global phenomena of bacterial resistance, inherited non-inherited, tolerance—associated with biofilm formation—are prompting dire predictions a post-antibiotic era in near future. These refer to increases morbidity mortality rates as consequence infections multidrug-resistant or pandrug-resistant microbial strains. In this context, we aimed highlight status resistance phenomenon significance virulence properties/fitness for human health review main strategies alternative complementary therapy, some them being already clinically applied clinical trials, others only foreseen research phase.
Язык: Английский
Процитировано
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