Celastrol boosts fluconazole efficacy against vaginal candidiasis: in vitro and in vivo evidence DOI Creative Commons
Fatma Al‐zahraa A. Yehia, Hisham A. Abbas,

Tarek M. Ibrahim

et al.

AMB Express, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 29, 2025

Candida albicans is a commensal fungus that naturally inhabits the vagina. However, overgrowth of C. can result in vulvovaginal candidiasis (VVC), one most prevalent fungal infections affecting women. The rapid emergence azole resistance albicans, addition to limited available antifungal agents, complicates treatment and emphasizes urgent need for novel therapeutic options. Efflux-mediated common mechanism fluconazole (FLZ)-resistant albicans. Combination therapy using natural compounds potential approach restore fluconazole's activity azole-resistant isolates via efflux pump inhibition. This study aimed evaluate ability celastrol, triterpene, retrieve FLZ against vitro vivo. Celastrol did not exhibit tested clinical isolates; however, sub-MIC celastrol inhibited rhodamine 6G (R6G) increased R6G accumulation inside celastrol-treated cells. Synergy was spotted between checkerboard assay. Quantification m-RNA levels efflux-mediated genes within demonstrated CDR1 overexpression. Upon treatment, significant decline ABC transporters transcript were detected. Moreover, molecular docking blocker successfully fits into target binding pockets. A negligible hemolytic effect human erythrocytes observed. In vivo model VVC, combination vaginal gel revealed drastic reduction burden with apparently normal tissue. promising findings strengthen its future use

Language: Английский

Biofilm Lifestyle in Recurrent Urinary Tract Infections DOI Creative Commons
Amr S. Abu Lila,

Azza A. H. Rajab,

Marwa H. Abdallah

et al.

Life, Journal Year: 2023, Volume and Issue: 13(1), P. 148 - 148

Published: Jan. 4, 2023

Urinary tract infections (UTIs) represent one of the most common that are frequently encountered in health care facilities. One main mechanisms used by bacteria allows them to survive hostile environments is biofilm formation. Biofilms closed bacterial communities offer protection and safe hiding, allowing evade host defenses hide from reach antibiotics. Inside communities, show an increased rate horizontal gene transfer exchange resistance virulence genes. Additionally, communication within orchestrate expression genes, which further cements infestation increases invasiveness infection. These facts stress necessity continuously updating our information understanding etiology, pathogenesis, eradication methods this growing public concern. This review seeks understand role formation recurrent urinary tact outlining underlying different uropathogens, addition shedding light on some strategies.

Language: Английский

Citations

64

Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens DOI Open Access
Simona Cavalu, Samar S. Elbaramawi, Ahmed G. Eissa

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13088 - 13088

Published: Oct. 28, 2022

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation biofilms. Quorum sensing (QS) orchestrates virulence and controls biofilm. Targeting promising approach overcome increment antibiotics. In a previous detailed in silico study, anti-QS activities twenty-two β-adrenoreceptor blockers were screened supposing atenolol as candidate. current study aims evaluate anti-QS, anti-biofilm anti-virulence blocker against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, Proteus mirabilis. An was conducted binding affinity S. marcescens SmaR QS receptor, P. aeruginosa QscR mirabilis MrpH adhesin. activity evaluated tested strains vitro vivo. present finding shows considerable ability compete proteins significantly downregulated expression QS- virulence-encoding genes. Atenolol showed significant reduction biofilm formation, enzyme production, motility. Furthermore, diminished capacity for killing protected mice. conclusion, has potential can be used adjuvant treatment aggressive infections.

Language: Английский

Citations

38

Diminishing the Pathogenesis of the Food-Borne Pathogen Serratia marcescens by Low Doses of Sodium Citrate DOI Creative Commons
Maan T. Khayat, Samar S. Elbaramawi, Shaimaa I. Nazeih

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(4), P. 504 - 504

Published: March 26, 2023

Protecting food from bacterial contamination is crucial for ensuring its safety and avoiding foodborne illness. Serratia marcescens one of the contaminants that can form biofilms pigments spoil product could cause infections illness to consumer. Food preservation essential diminish such or at least reduce their pathogenesis; however, it should not affect odor, taste, consistency must be safe. Sodium citrate a well-known safe additive current study aims evaluate anti-virulence anti-biofilm activity low concentrations against S. marcescens. The antibiofilm activities sodium were evaluated phenotypically genotypically. results showed significant effect on decreasing biofilm formation other virulence factors, as motility production prodigiosin, protease, hemolysins. This owed downregulating virulence-encoding genes. An in vivo investigation was conducted mice histopathological examination isolated tissues liver kidney confirmed citrate. In addition, an silico docking binding ability quorum sensing (QS) receptors regulates virulence. marked virtual compete QS proteins, which explain citrate's effect. conclusion, used prevent by bacteria.

Language: Английский

Citations

30

Drug repositioning: doxazosin attenuates the virulence factors and biofilm formation in Gram-negative bacteria DOI
Mahmoud A. Elfaky, Samar S. Elbaramawi, Ahmed G. Eissa

et al.

Applied Microbiology and Biotechnology, Journal Year: 2023, Volume and Issue: 107(11), P. 3763 - 3778

Published: April 20, 2023

Language: Английский

Citations

29

Prevalence of different virulence factors and their association with antimicrobial resistance among Pseudomonas aeruginosa clinical isolates from Egypt DOI Creative Commons
Eva A. Edward,

Marwa R. El Shehawy,

Alaa Abouelfetouh

et al.

BMC Microbiology, Journal Year: 2023, Volume and Issue: 23(1)

Published: June 3, 2023

Abstract Background Emergence of multi-drug resistant Pseudomonas aeruginosa, coupled with the pathogen’s versatile virulence factors, lead to high morbidity and mortality rates. The current study investigated potential association between antibiotic resistance production factors among P. aeruginosa clinical isolates collected from Alexandria Main University Hospital in Egypt. We also evaluated phenotypic detection reflect as detected by genes presence. role alginate formation biofilms effect ambroxol, a mucolytic agent, on inhibition biofilm were investigated. Results A phenotype was 79.8% isolates. most predominant factor (89.4%), while DNase least (10.6%). Pigment significantly associated ceftazidime susceptibility, phospholipase C linked sensitivity cefepime, intermediate meropenem. Among tested genes, lasB algD showed highest prevalence rates (93.3% 91.3%, respectively), toxA plcN ones (46.2% 53.8%, respectively). Significant exoS aztreonam plcH piperacillin-tazobactam susceptibility observed. There significant correlation alkaline protease , ; pigment presence gelatinase existence . Ambroxol anti-biofilm activity (5% 92%). Quantitative reverse transcriptase polymerase chain reaction that not an essential matrix component biofilms. Conclusions High isolates’ commonly used antimicrobials would increase infections. displayed action could be suggested alternative treatment option, yet vivo studies are required confirm these findings. recommend active surveillance antimicrobial determinant for better understanding coregulatory mechanisms.

Language: Английский

Citations

27

What’s old is new again: Insights into diabetic foot microbiome DOI Open Access

Azza A. H. Rajab,

Wael A. H. Hegazy

World Journal of Diabetes, Journal Year: 2023, Volume and Issue: 14(6), P. 680 - 704

Published: June 14, 2023

Diabetes is a chronic disease that considered one of the most stubborn global health problems continues to defy efforts scientists and physicians. The prevalence diabetes in population grow alarming levels year after year, causing an increase incidence complications care costs all over world. One major complication high susceptibility infections especially lower limbs due immunocompromised state diabetic patients, which definitive factor cases. Diabetic foot continue be common patients are associated with risk serious such as bone infection, limb amputations, life-threatening systemic infections. In this review, we discussed circumstances infection well some commonly isolated pathogens from related virulence behavior. addition, shed light on different treatment strategies aim at eradicating infection.

Language: Английский

Citations

27

Synergistic Benefits: Exploring the Anti-Virulence Effects of Metformin/Vildagliptin Antidiabetic Combination against Pseudomonas aeruginosa via Controlling Quorum Sensing Systems DOI Creative Commons
Maan T. Khayat, Hisham A. Abbas, Tarek S. Ibrahim

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1442 - 1442

Published: May 14, 2023

The repurposing of drugs is one the most competent strategies for discovering new antimicrobial agents. Vildagliptin a dipeptidyl peptidase-4 inhibitor (DPI-4) that used effectively in combination with metformin to control blood glucose levels diabetic patients. This study was designed evaluate anti-virulence activities this against clinically important pathogens, Pseudomonas aeruginosa. current findings show significant ability vildagliptin-metformin diminish biofilm formation, bacterial motility, and production virulent extracellular enzymes pyocyanin pigment. Furthermore, drug significantly increased susceptibility P. aeruginosa oxidative stress, indicating immunity enhancement eradication cells. In compliance vitro findings, histopathological photomicrographs mice showed considerable protective effect metformin-vildagliptin aeruginosa, revealing relief inflammation due aeruginosa-induced pathogenesis. mainly employs quorum sensing (QS) systems its huge arsenal virulence factors. can be interrupted by anti-QS both vildagliptin, as exhibited affinity QS receptors. Additionally, downregulated expression main three QS-encoding genes These at very low concentrations (10, 1.25 mg/mL, respectively) compared (850, 50 diabetes.

Language: Английский

Citations

25

Utilization of zein nano-based system for promoting antibiofilm and anti-virulence activities of curcumin against Pseudomonas aeruginosa DOI Creative Commons
Shaimaa M. Badr-Eldin, Hibah M. Aldawsari, Osama A. A. Ahmed

et al.

Nanotechnology Reviews, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 1, 2024

Abstract Bacterial biofilms contribute to increased pathogenesis and bacterial resistance. Biofilms can enhance pathogenicity by shielding bacteria from the immune system antibiotics, they are associated with persistent infections. Additionally, antibiotic resistance mechanisms within make them challenging treat, emphasizing need for strategies be addressed. Mitigating virulence is a promising strategy that could ease their eradication host immunity without stressing induce The merits of this augmented when using safe anti-virulence candidates in proper formulations. current study aimed evaluate antibiofilm efficacy curcumin–zein nanoparticles against Pseudomonas aeruginosa . In vitro investigations were performed assess effect on biofilm formation, motility, production factors, including proteases, hemolysins, pyocyanin, comparison bulk curcumin. Furthermore, expression genes encode quorum sensing (QS) systems regulate was assessed. An silico done affinity curcumin QS receptors. an vivo protection assay inhibitory our preparation diminishing P. aeruginosa’s capacity pathogenesis. results showed significant activities compared These attributed curcumin’s interfering its virulence. conclusion, acquires anti-QS, anti-virulence, vastly enhanced upon loading zein nanoparticles.

Language: Английский

Citations

11

Biofilm Resilience: Molecular Mechanisms Driving Antibiotic Resistance in Clinical Contexts DOI Creative Commons
Ahmad Almatroudi

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

Citations

1

Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities DOI Creative Commons
Abrar K. Thabit, Khalid Eljaaly, Ayat Zawawi

et al.

Microorganisms, Journal Year: 2022, Volume and Issue: 10(10), P. 1976 - 1976

Published: Oct. 6, 2022

The targeting of bacterial virulence is proposed as a promising approach to overcoming the resistance development antibiotics. Salmonella enterica one most important gut pathogens that cause wide diversity local and systemic illnesses. controlled by interplayed systems namely Quorum sensing (QS) type three secretion system (T3SS). Furthermore, spy on host cell via adrenergic hormones enhancing its virulence. current study explores possible anti-virulence activities β-adrenoreceptor blocker atenolol against S. serovar Typhimurium in vitro, silico, vivo. present findings revealed significant ability diminish typhimurium biofilm formation, invasion into HeLa cells, intracellular replication inside macrophages. Atenolol significantly downregulated encoding genes T3SS-type II, QS receptor Lux analogs sdiA, norepinephrine membranal sensors qseC qseE. Moreover, protected mice typhimurium. For testing mechanisms for activities, an silico molecular docking was conducted assess binding SdiA QseC. showed compete targets. In conclusion, candidate alleviate pathogenesis T3SS besides diminishing eavesdropping cells.

Language: Английский

Citations

29