Broad-Spectrum Gramicidin S Derivatives with Potent Activity Against Multidrug-Resistant Gram-Negative ESKAPE Pathogens DOI Creative Commons

John T. Kalyvas,

Yifei Wang, Ornella Romeo

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(5), P. 423 - 423

Published: April 22, 2025

Background/Objectives: Multidrug-resistant Gram-negative ESKAPE pathogens, including E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii, pose a significant global health threat. Gramicidin S, potent cyclic antimicrobial peptide, is largely ineffective against these bacteria, its high haemolytic toxicity limits clinical usage. This study reports on several novel gramicidin S analogues with improved efficacy safety profiles multidrug-resistant bacteria. Methods: A total of 19 derivatives were synthesised using Fmoc-based solid-phase peptide synthesis targeted substitutions to enhance cationicity modulate hydrophobicity. Minimum inhibitory concentrations (MICs) determined standard Gram-positive strains. Haemolytic in vitro nephrotoxicity evaluated human red blood cells HEK-293 cells, respectively. All peptides characterised by RP-HPLC HRMS. Results: The selective incorporation DArg Trp significantly enhanced activity bacteria while reducing cytotoxicity. Peptide 8 the therapeutic index (TI) coli 10-fold (MIC: µg/mL; TI: 4.10) compared 32 0.38). 9 exhibited an 8-fold potency increase pneumoniae 25-fold TI improvement. aeruginosa over 7 showed 27-fold enhancement. active retained broad-spectrum S. aureus, MRSA. Conclusions: findings highlight critical role balancing hydrophobicity overcome species-specific resistance mechanisms. Our demonstrate reduced parent providing robust platform for development new antibiotics bacterial pathogens.

Language: Английский

Measuring water pollution effects on antimicrobial resistance through explainable artificial intelligence DOI Creative Commons
A. Monaco,

Mario Caruso,

Loredana Bellantuono

et al.

Environmental Pollution, Journal Year: 2025, Volume and Issue: unknown, P. 125620 - 125620

Published: Jan. 1, 2025

Language: Английский

Citations

1

Complete genome sequence of Pseudomonas aeruginosa YK01, a sequence type 16 isolated from a patient with keratitis DOI Creative Commons
Shuo Jiang,

Mengmin Ye,

Ke Liu

et al.

BMC Genomic Data, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 22, 2025

Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is frequently associated with multidrug resistance and global epidemic outbreaks, contributing significantly to morbidity mortality in hospitalized patients. However, P. aeruginosa belonging the sequence type (ST) 16 was rarely reported. Here, this report presents complete genome of YK01, ST16 isolate from patient keratitis. The reference YK01 expected provide valuable data for investigating its genomic population, enhancing understanding genetic basis species complex. A 6.3 Mb obtained by combining Illumina 150-bp short reads Nanopore long reads. assembly fully chromosomal size 6,183,266 bp, presenting GC content 66.7%, plasmid 46,067 59.0%. Predicted features include 5,709 CDS, 12 rRNAs, 63 tRNAs, 4 ncRNAs, 5,788 genes. To our knowledge, represents first ST16, providing crucial information further comparative analysis.

Language: Английский

Citations

1

Impact of Antimicrobial Resistance of Pseudomonas aeruginosa in Urine of Small Companion Animals in Global Context: Comprehensive Analysis DOI Creative Commons
Ana Pereira, Telma de Sousa, Catarina Silva

et al.

Veterinary Sciences, Journal Year: 2025, Volume and Issue: 12(2), P. 157 - 157

Published: Feb. 11, 2025

The isolation of multidrug-resistant (MDR) bacteria from the urinary tracts pets is increasingly common, particularly in animals with concurrent health conditions. Pseudomonas aeruginosa (PA) one most significant antimicrobial-resistant affecting cats and dogs within European Union (EU). This study aims to review prevalence antimicrobial resistance patterns PA isolated urine samples small globally. pathogen known for its opportunistic infections a concern veterinary medicine due inherent multiple antibiotics ability acquire additional mechanisms. seeks enhance educational initiatives regarding management emerging MDR bacteria.

Language: Английский

Citations

1

Current trends in the epidemiology of multidrug-resistant and beta-lactamase-producing Pseudomonas aeruginosa in Asia and Africa: a systematic review and meta-analysis DOI Creative Commons
Mohd Zulkifli Salleh, Nik Mohd Noor Nik Zuraina, Zakuan Zainy Deris

et al.

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e18986 - e18986

Published: Feb. 24, 2025

Pseudomonas aeruginosa continues to be a significant contributor high morbidity and mortality rates worldwide, particularly due its role in severe infections such as hospital-acquired conditions, including ventilator-associated pneumonia various sepsis syndromes. The global increase antimicrobial-resistant (AMR) P. strains has made these more difficult treat, by limiting the effective drug options available. This systematic review meta-analysis aim provide an updated summary of prevalence AMR over past 5 years. A search was performed across three major electronic databases—PubMed, ScienceDirect, Web Science—yielding 40 eligible studies published between 2018 2023. Using random-effects model, our estimated that overall Asia Africa years 22.9% (95% CI [14.4–31.4]). for multidrug-resistant (MDR) extensively drug-resistant (XDR) were found 46.0% [37.1–55.0]) 19.6% [4.3–34.9]), respectively. Furthermore, extended-spectrum β-lactamase- metallo-β-lactamase-producing 33.4% [23.6–43.2]) 16.0% [9.8–22.3]), Notably, resistance β-lactams used treating pseudomonal alarmingly high, with 84.4% 100.0% cephalosporins, 40% isolates showed penicillins. Our analysis identified lowest last-resort antimicrobials, 0.3% [0.0–1.3]) polymyxin B 5.8% [1.5–10.2]) colistin/polymyxin E. low polymyxins suggest antibiotics remain against MDR . However, findings also highlight critical public health threat posed , concerning β-lactam antibiotics. underscores need carefully planned intervention strategies, development new address growing challenge resistance. Developing robust antibiotic treatment protocols is essential better management control globally. Therefore, continued research international collaboration vital tackle this escalating challenge. study protocol registered International Prospective Register Systematic Reviews (PROSPERO), under registration number CRD42023412839.

Language: Английский

Citations

1

Activity of Antiseptics Against Pseudomonas aeruginosa and Its Adaptation Potential DOI Creative Commons
Tomasz M. Karpiński,

Marzena Korbecka-Paczkowska,

Mark Stasiewicz

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(1), P. 30 - 30

Published: Jan. 3, 2025

Background/Objectives: Pseudomonas aeruginosa rapidly acquires antibiotic resistance and demonstrates increasing tolerance to antiseptics. This study evaluated the activity of eight antiseptics against P. aeruginosa, assessed its ability develop adaptation these antiseptics, and, for first time, determined Karpinski Adaptation Index (KAI) this bacterium. Methods: The minimal inhibitory concentration (MIC), susceptibility antibiotics, bactericidal time according EN 1040:2005, potential, KAI strains were evaluated. Results: most effective based on MIC activity, octenidine dihydrochloride (OCT; mean 11.3 ± 4.5 µg/mL), polyhexamethylene biguanide (PHMB; 22.6 8.0 chlorhexidine digluconate (CHX; 26.6 14.4 µg/mL). Sodium hypochlorite (NaOCl) ethacridine lactate (ET) showed moderate while boric acid (BA), povidone-iodine (PVI), potassium permanganate (KMnO4) exhibited weakest activity. values NaOCl (95 15.4 µg/mL) KMnO4 (>10 mg/mL) close or exceeded clinical concentrations used in commercial products. OCT, CHX, PVI fastest effect within 1 min. Bactericidal times up 15 min PHMB, 60 ET, more than BA, NaOCl, KMnO4. lowest values, indicating a low risk, observed OCT (0.12), PHMB (0.19), BA (0.19). Moderate risk was noted (0.21), CHX (0.29), ET (0.47). highest signifying very high found (1.0) (≥1.0). Conclusions: Antiseptics like partially can be critical quick antibacterial action infected wounds, agents such as might reserved cases where prolonged contact are possible. Given rapid currently use, reconsideration their effectiveness treating skin mucous membrane infections is recommended.

Language: Английский

Citations

0

Exploring Antibacterial Properties of Marine Sponge-Derived Natural Compounds: A Systematic Review DOI Creative Commons
Cintia Cristina Santi Martignago, Camila de Souza Barbosa,

Homero Garcia Motta

et al.

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(1), P. 43 - 43

Published: Jan. 16, 2025

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring natural products, particularly those of marine origin, promising candidates for antimicrobial drugs. Marine sponges, particular, are interest because their production secondary metabolites (SM), which serve chemical defenses against predators pathogens. These exhibit a wide range therapeutic properties, including activity. systematic review examines recent advancements identifying new sponge-derived compounds with activity, specifically targeting Pseudomonas aeruginosa, prevalent Gram-negative pathogen highest incidence rates clinical settings. selection criteria focused on reported Minimum Inhibitory Concentration (MIC) values. identified SM include alkaloids, sesterterpenoids, nitrogenous diterpene, bromotyrosine-derived derivatives. structural features active selected may provide foundational framework developing new, highly bioactive agents.

Language: Английский

Citations

0

Phage treatment of multidrug-resistant bacterial infections in humans, animals, and plants: The current status and future prospects DOI Creative Commons

Omor Faruk,

Zilhas Ahmed Jewel,

Sanjoy Bairagi

et al.

Infectious Medicine, Journal Year: 2025, Volume and Issue: 4(1), P. 100168 - 100168

Published: Feb. 6, 2025

Phages, including the viruses that lyse bacterial pathogens, offer unique therapeutic advantages, their capacity to antibiotic-resistant bacteria and disrupt biofilms without harming host microbiota. The lack of new effective antibiotics growing limitations existing have refocused attention on phage therapy as an option in complex clinical cases such burn wounds, cystic fibrosis, pneumonia. This review describes preclinical studies which has been both human veterinary medicine, agricultural context. In addition, critical challenges, narrow range bacteriophages, possibility resistance, regulatory constraints widespread use therapy, are addressed. Future directions include optimizing through strategies ranging from cocktails broadening genetic modification, using phages vaccines or biocontrol agents. future, if can be efficiently delivered, maintained a stable state, phage-antibiotic synergy achieved, will much needed treatment options. However, successful implementation within current standards practice also require considerable development infrastructure greater public acceptance. closing, this highlights promise backup substitute for antibiotics. It proposes role significant adjunct to, even replacement for, treating multidrug-resistant infections.

Language: Английский

Citations

0

Comparison between the effect of gentamicin and purified Lactobacillus salivarius exopolysaccharides on the biofilm formation and Pseudomonas aeruginosa Rh1I gene expression DOI

H. Ayaat,

Ibtesam Ghadban Auda,

Likaa Hamied Mahdi

et al.

Gene Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102164 - 102164

Published: Feb. 1, 2025

Language: Английский

Citations

0

Proteome-Wide Identification of Druggable Targets and Inhibitors for Multidrug-Resistant Pseudomonas aeruginosa Using an Integrative Subtractive Proteomics and Virtual Screening Approach DOI Creative Commons
Divya Vemula, Vasundhra Bhandari

Heliyon, Journal Year: 2025, Volume and Issue: 11(4), P. e42584 - e42584

Published: Feb. 1, 2025

Pseudomonas aeruginosa, a versatile and antibiotic-resistant gram-negative pathogen, poses critical threat to both immunocompromised immunocompetent populations, underscoring the urgent need for new therapeutic targets. This study applies an extensive subtractive proteomics approach identify viable drug targets within core proteome of P. aeruginosa PAO1, analyzing total 5563 proteins. Through rigorous, multi-stage process, we excluded human homologs, identified essential proteins, mapped functional pathways, determined subcellular localization, assessed virulence resistance factors. comprehensive analysis led identification three novel, druggable integral aeruginosa's pathogenicity multidrug resistance: preprotein translocase subunit SecD, chemotaxis-specific methyl esterase, imidazole glycerol phosphate synthase HisF2. Following this, inverse virtual screening 464,867 compounds from VITAS-M library, performed using Schrödinger's Glide module, initially pinpointed 15 potent hits with favorable binding affinities pharmacokinetic profiles as confirmed by QikProp analysis. Subsequent molecular dynamics, MMPBSA DFT calculations refined these promising candidates: STK417467 HisF2, STL321396 methylesterase, STL243336 SecD. These show strong potential inhibitors could be developed further agents against multidrug-resistant infections. provides robust computational framework discovery candidate inhibitors, marking significant step toward effective treatments resistant

Language: Английский

Citations

0

Broad-Spectrum Gramicidin S Derivatives with Potent Activity Against Multidrug-Resistant Gram-Negative Eskape Pathogens DOI
Andrew D. Abell,

John T. Kalyvas,

Yifei Wang

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0