The Evolution of Antimicrobial Resistance in Acinetobacter baumannii and New Strategies to Fight It

Antibiotics, Journal Year: 2025, Volume and Issue: 14(1), P. 85 - 85

Published: Jan. 14, 2025

Acinetobacter baumannii is considered one of the prioritized ESKAPE microorganisms for research and development novel treatments by World Health Organization, especially because its remarkable persistence drug resistance. In this review, we describe how can be acquired enzymatic degradation antibiotics, target site modification, altered membrane permeability, multidrug efflux pumps, their ability to form biofilms. Also, evolution resistance in A. baumannii, which mainly driven mobile genetic elements, reported, with particular reference plasmid-associated resistance, islands, insertion sequences. Finally, an overview existing, new, alternative therapies provided.

Language: Английский

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Prophylactic phage administration provides a time window for delayed treatment of vancomycin-resistant Enterococcus faecalis in a murine bacteremia model

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 24, 2025

Introduction Vancomycin-resistant Enterococcus faecalis (VRE) poses a significant challenge in clinical settings due to its resistance multiple antibiotics. Phage therapy offers promising alternative address this crisis. However, critical gaps remain regarding optimal dosing, therapeutic design, and treatment timing for phage targeting VRE-induced bacteremia. Methods The biological genomic characteristics of novel lytic specific VRE were investigated. Its vitro bactericidal antibiofilm activities evaluated, along with synergy antimicrobial agents. In safety protective efficacy assessed using mouse bacteremia model. impact on gut microbiota was examined through 16S rDNA gene sequencing. Results We isolated characterized phage, vB_EfaS-1017, vancomycin-resistant E. . This features circular, double-stranded DNA genome (40,766 bp), sharing 91.19% identity 79% coverage vB_EfaS_SRH2. vB_EfaS-1017 exhibited robust activity demonstrated levofloxacin. Safety assessments confirmed non-toxicity mammalian cells lack hemolytic activity. model, alone rescued 60% infected mice, while combining levofloxacin increased survival 80%. Prophylactic administration 24 hours prior infection failed prevent mortality. combination prophylactic delayed compared 100% mortality the group. Additionally, helped maintain or restore balance. Discussion These findings underscore potential phage-antibiotic combinations as superior strategy against infections. observed between phages antibiotics highlights approach overcoming bacterial improving outcomes. Furthermore, may provide time window effective treatment. Further preclinical research is essential refine protocols application.

Language: Английский

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Phage therapy: an alternative treatment modality for MDR bacterial infections

Infectious Diseases, Journal Year: 2024, Volume and Issue: 56(10), P. 785 - 817

Published: July 17, 2024

The increasing global incidence of multidrug-resistant (MDR) bacterial infections threatens public health and compromises various aspects modern medicine. Recognising the urgency this issue, World Health Organisation has prioritised development novel antimicrobials to combat ESKAPEE pathogens. Comprising

Language: Английский

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Phage vB_Kpn_HF0522: Isolation, Characterization, and Therapeutic Potential in Combatting K1 Klebsiella pneumoniae Infections

Infection and Drug Resistance, Journal Year: 2025, Volume and Issue: Volume 18, P. 803 - 818

Published: Feb. 1, 2025

Purpose: Klebsiella pneumoniae is a globally prevalent pathogen responsible for severe hospital- and community-acquired infections, presents significant challenges clinical management. Current therapeutic strategies are no longer able to meet the needs; therefore, there an urgent need develop novel strategies. This study aimed evaluate efficacy of phage therapy in treating bacterial infections. Methods: Isolated vB_Kpn_HF0522 morphology were observed using transmission electron microscopy. Analysis characteristics, including optimal multiplicity infection (MOI), one-step growth curve, host range, stability different environments, adsorption capacity. The genomic sequence was analyzed explore evolutionary relationships. effect on biofilms assessed crystal violet staining assay. Galleria mellonella ( G. ) model mouse models established practical application potential fitness cost phage-resistant bacteria. Results: Phage isolated from hospital sewage experimental studies. Genome analysis revealed that double-stranded linear DNA virus. Biological characterization demonstrated this specifically targets serotype K1 K. with (MOI) 0.01, effectively disrupting inhibiting growth. rate remained largely unchanged after resistance mutation, but mice infected mutant strain showed significantly higher survival rates than those wild-type strain. increased 12.5% 75%, inhibited incisional surgical site infections alleviated inflammatory response mice. Conclusion: These findings indicate has specific may serve as antimicrobial agent research anti-infective therapy. Keywords: vB_Kpn_HF0522, therapy, , resistance, infection, biofilm

Language: Английский

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Optimizing phage therapy for carbapenem-resistant Enterobacter cloacae bacteremia: insights into dose and timing

Antimicrobial Agents and Chemotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

ABSTRACT The increase in multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) infections, particularly those resistant to carbapenems, underscores the urgent need for alternative therapies. Phage therapy, with its specific bactericidal action, offers a promising solution. However, there remains shortage of well-characterized ECC-targeting phages, and dosing timing optimization ECC-specific phage cocktails is largely unexplored. In this study, we isolated characterized three novel lytic phages diverse genome sizes host ranges. Notably, ФEBU8 demonstrated broad-spectrum activity, lysing both species Acinetobacter baumannii . ФECL22 displayed stability across wide temperature range (4–50°C), pH tolerance (6–10), burst size 19 PFU/cell, OmpA identified as receptor. Our formulated cocktail, comprising ФEBU8, ФECL22, ФECL30, effectively rescued mice E. bacteremia dose-dependent manner, mid-dose regimen showing strong efficacy. Immediate administration achieved full survival, whereas combined prophylactic therapeutic (“−24 + 6”) also resulted 100% survival. These findings highlight critical roles optimizing therapy carbapenem-resistant use providing valuable window delayed treatment strategy combating severe bacterial infections.

Language: Английский

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Characterization of a novel lytic phage vB_AbaM_AB4P2 encoding depolymerase and its application in eliminating biofilms formed by Acinetobacter baumannii

BMC Microbiology, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 8, 2025

Acinetobacter baumannii strains are a primary cause of hospital-acquired infections. This bacterium frequently causes biofilm-related infections, notably ventilator-associated pneumonia and catheter-related which exhibit remarkable resistance to antibiotic treatment, posing severe challenge in the prevention A. Therefore, strategies eliminate biofilm catheters becoming increasingly important. Phages capable lysing bacteria have certain effect on ablation biofilms. Sewage treatment plant water was collected for isolation phages. The morphological, host range, one-step growth, temperature pH stability, bactericidal activity, sequencing genomic analysis were performed characterize isolated phage. three-dimensional structure tail fiber protein predicted by AlphaFold3. efficacy phage clearing biofilms from 24-well plates PVC also evaluated. In this study, lytic vB_AbaM_AB4P2 sewage water, showing clear plaque with halo zone. One-step growth assays unveiled 20-minute latent period burst size 61 forming unit/cell (PFU/cell). At same time, AB4P2 exhibited stability at 3–11 temperatures 30–70 °C. Its dsDNA genome is composed 45,680 bp G + C content 46.13%. Genomic phylogenetic situated as new species Caudoviricetes class. possesses pectin lyase-like domain that linked depolymerase playing crucial role disrupting Additionally, it encodes lysis cassette comprising endolysin, holin Rz-like spanin, yet lacks any genes responsible virulence factors. Phage can completely inhibit 16 h. plate polyvinyl chloride (PVC) catheter model experiments, achieved significant rate effectively killed live bacterial cells biofilm. had good environmental strong ability destroy formed baumannii. It exhibits promising potential development an alternative disinfectant against hospital. Not applicable.

Language: Английский

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Recent insights on phage therapy against multidrug-resistant Acinetobacter baumannii

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

Published: March 12, 2025

Abstract Acinetobacter baumannii is a prevalent clinical pathogen commonly found to be multidrug-resistant (MDR), causing serious life-threatening infections, particularly hospital-acquired infections with limited therapeutic options. The MDR phenotype developed against this critical increasingly globally, reaching pan-drug-resistant conferring non-susceptibility all antimicrobials used in its treatment according the standard guidelines. Therefore, it develop innovative approaches, such as phage therapy, considering rise drug-resistant A. infections. In review, we highlight and discuss up-to-date antimicrobial resistance of , use phages, their limitations, future perspectives treating addition, combination phages antimicrobials, preclinical studies including pharmacokinetics pharmacodynamics properties have been discussed.

Language: Английский

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Phage Therapy: An Alternative Approach to Combat Multi-drug Resistant Infections in Cystic Fibrosis

Published: June 21, 2024

In this review we aim to address the current status of phage therapy in management multidrug-resistant infections, from compassionate use cases ongoing clinical trials, as well challenges approach presents particular context CF patients.

Language: Английский

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Phage Therapy: An Alternative Approach to Combating Multidrug-Resistant Bacterial Infections in Cystic Fibrosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8321 - 8321

Published: July 30, 2024

Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections a variety of pathogens that difficult eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus. These still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure antibiotics combination favors development spread multi-resistant bacteria; thus, alternative strategies is crucial counter antimicrobial resistance. In this context, phage therapy, i.e., use phages, viruses specifically infect bacteria, has become promising strategy. review, we aim address current status management multidrug-resistant infections, from compassionate cases ongoing clinical trials, well challenges approach presents particular context patients.

Language: Английский

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Phage-Based Therapy in Combination with Antibiotics: A Promising Alternative against Multidrug-Resistant Gram-Negative Pathogens

Pathogens, Journal Year: 2024, Volume and Issue: 13(10), P. 896 - 896

Published: Oct. 14, 2024

The continued rise in antimicrobial resistance poses a serious threat to public health worldwide. use of phages that can have bactericidal activity without disrupting the normal flora represents promising alternative treatment method. This practice has been successfully applied for decades, mainly Eastern Europe, and recently used as an emergency therapy compassionate care United States. Here, we provide comprehensive review pre-clinical clinical applications phage concerning three major Gram-negative pathogens:

Language: Английский

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