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Antibiotics (Basel, Switzerland) Jun 2024() is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs...
() is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug library containing 3048 marketed and pharmacopeial drugs or compounds was screened at 20 μM against type strain 19977 in 7H9 medium, and 62 hits with potential antimicrobial activity against were identified. Among them, bithionol, a clinically approved antiparasitic agent, showed excellent antibacterial activity and inhibited the growth of three different subtypes of from 0.625 μM to 2.5 μM. We confirmed the bactericidal activity of bithionol by the MBC/MIC ratio being ≤4 and the time-kill curve study and also electron microscopy study. Interestingly, it was found that at 128 μg/mL, bithionol could completely eliminate biofilms after 48h, demonstrating an outstanding antibiofilm capability compared to commonly used antibiotics. Additionally, bithionol could eliminate 99.9% of biofilm bacteria at 64 μg/mL, 99% at 32 μg/mL, and 90% at 16 μg/mL. Therefore, bithionol may be a potential candidate for the treatment of infections due to its significant antimicrobial and antibiofilm activities.
PubMed: 38927195
DOI: 10.3390/antibiotics13060529 -
Antibiotics (Basel, Switzerland) Jun 2024The prevalence of carbapenem-resistant has dramatically increased over the last decade, and antibiotics alone are not enough to eradicate infections caused by this...
The prevalence of carbapenem-resistant has dramatically increased over the last decade, and antibiotics alone are not enough to eradicate infections caused by this opportunistic pathogen. Phage therapy is a fresh treatment that can be administered under compassionate use, particularly against chronic cases. However, it is necessary to thoroughly characterize the virus before therapeutic application. Our work describes the discovery of the novel sequenced bacteriophage, vB_PaeP-F1Pa, containing an integrase, performs a phylogenetical analysis, describes its stability at a physiological pH and temperature, latent period (40 min), and burst size (394 ± 166 particles per bacterial cell), and demonstrates its ability to infect MDR and XDR strains. Moreover, this novel bacteriophage was able to inhibit the growth of bacteria inside preformed biofilms. The present study offers a road map to analyze essential areas for successful phage therapy against MDR and XDR infections, and shows that a phage containing an integrase is also able to show good in vitro results, indicating that it is very important to perform a genomic analysis before any clinical use, in order to prevent adverse effects in patients.
PubMed: 38927189
DOI: 10.3390/antibiotics13060523 -
Antibiotics (Basel, Switzerland) Jun 2024, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand...
, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand currently available antifungals. Direct current (DC) has demonstrated a promising antimicrobial effect and synergistic effect with antimicrobials against various infections. Here, we first found DC exerted a killing effect on planktonic and biofilm cells. Moreover, DC showed a synergistic effect with fluconazole (FLC) and amphotericin B (AMB). Notably, near-to-complete eradication of AMB-tolerant biofilm persisters was achieved upon DC treatment. Next, the mechanism of action of DC was explored through mapping the genes and proteomic profiles of DC-treated . The multi-omics analysis, quantitative real-time PCR and assay of reactive oxygen species (ROS) demonstrated DC exerted an antifungal effect on by increasing cellular oxidative stress. As revealed by multiple analyses (e.g., protein assay based on absorbance at 280 nm and rhodamine 6G assay), DC was able to enhance membrane permeability, inhibit drug efflux and increase cellular FLC/AMB concentration of , thereby mediating its synergism with the antifungals. Furthermore, DC inhibited superoxide dismutase 2 (SOD2) expression and manganese-containing SOD (Mn SOD) activity, leading to ROS production and enhanced killing of biofilm persisters. The current findings demonstrate that the adjunctive use of DC in combination with antifungals is a promising strategy for effective control of infections and management of antifungal resistance/tolerance in biofilms.
PubMed: 38927187
DOI: 10.3390/antibiotics13060521 -
Antibiotics (Basel, Switzerland) May 2024Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial... (Review)
Review
Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial communities, comprising bacteria and fungi, exhibit resilience against antibiotics and host immune responses. Bacterial species such as , , , and commonly form biofilms on medical devices, exacerbating infection risks. Neonates and children, particularly those in intensive care units, are highly susceptible to biofilm-associated infections due to the prolonged use of invasive devices, such as central lines and endotracheal tubes. Enteral feeding tubes, crucial for neonatal nutritional support, also serve as potential sites for biofilm formation, contributing to recurrent microbial contamination. Moreover, species, including , present emerging challenges in neonatal care, with multi-drug resistant strains posing treatment complexities. Current antimicrobial therapies, while important in managing infections, often fall short in eradicating biofilms, necessitating alternative strategies. The aim of this review is to summarize current knowledge regarding antibiofilm strategies in neonates and in children. Novel approaches focusing on biofilm inhibition and dispersal show promise, including surface modifications, matrix-degrading enzymes, and quorum-sensing inhibitors. Prudent use of medical devices and exploration of innovative antibiofilm therapies are imperative in mitigating neonatal and pediatric biofilm infections.
PubMed: 38927176
DOI: 10.3390/antibiotics13060509 -
Antibiotics (Basel, Switzerland) May 2024Slow-growing nontuberculous mycobacteria (NTMs) are highly prevalent and routinely cause opportunistic intracellular infectious disease in immunocompromised hosts.
OBJECTIVES
Slow-growing nontuberculous mycobacteria (NTMs) are highly prevalent and routinely cause opportunistic intracellular infectious disease in immunocompromised hosts.
METHODS
The activity of the triple combination of antibiotics, clarithromycin (CLR), rifabutin (RFB), and clofazimine (CFZ), was evaluated and compared with the activity of single antibiotics as well as with double combinations in an in vitro biofilm assay and an in vivo murine model of subsp. () lung infection.
RESULTS
Treatment of 1-week-old biofilms with the triple combination exerted the strongest effect of all (0.12 ± 0.5 × 10 CFU/mL) in reducing bacterial growth as compared to the untreated (5.20 ± 0.5 × 10/mL) or any other combination (≥0.75 ± 0.6 × 10/mL) by 7 days. The treatment of mice intranasally infected with with either CLR and CFZ or the triple combination provided the greatest reduction in CLR-sensitive bacterial counts in both the lung and spleen compared to any single antibiotic or remaining double combination by 4 weeks posttreatment. After 4 weeks of treatment with the triple combination, there were no resistant colonies detected in mice infected with a CLR-resistant strain. No clear relationships between treatment and spleen or lung organ weights were apparent after triple combination treatment.
CONCLUSIONS
The biofilm assay data and mouse disease model efficacy results support the further investigation of the triple-antibiotic combination.
PubMed: 38927142
DOI: 10.3390/antibiotics13060475 -
Biomolecules Jun 2024Leucine residues are commonly found in the hydrophobic face of antimicrobial peptides (AMPs) and are crucial for membrane permeabilization, leading to the cell death of...
Leucine residues are commonly found in the hydrophobic face of antimicrobial peptides (AMPs) and are crucial for membrane permeabilization, leading to the cell death of invading pathogens. Melittin, which contains four leucine residues, demonstrates broad-spectrum antimicrobial properties but also significant cytotoxicity against mammalian cells. To enhance the cell selectivity of melittin, this study synthesized five analogs by replacing leucine with its structural isomer, 6-aminohexanoic acid. Among these analogs, Mel-LX3 exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Importantly, Mel-LX3 displayed significantly reduced hemolytic and cytotoxic effects compared to melittin. Mechanistic studies, including membrane depolarization, SYTOX green uptake, FACScan analysis, and inner/outer membrane permeation assays, demonstrated that Mel-LX3 effectively permeabilized bacterial membranes similar to melittin. Notably, Mel-LX3 showed robust antibacterial activity against methicillin-resistant (MRSA) and multidrug-resistant (MDRPA). Furthermore, Mel-LX3 effectively inhibited biofilm formation and eradicated existing biofilms of MDRPA. With its improved selective antimicrobial and antibiofilm activities, Mel-LX3 emerges as a promising candidate for the development of novel antimicrobial agents. We propose that the substitution of leucine with 6-aminohexanoic acid in AMPs represents a significant strategy for combating resistant bacteria.
Topics: Melitten; Biofilms; Pseudomonas aeruginosa; Microbial Sensitivity Tests; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Humans; Hemolysis; Aminocaproic Acid; Gram-Negative Bacteria; Animals
PubMed: 38927102
DOI: 10.3390/biom14060699 -
Biomolecules May 2024This study utilized phytochemical screening to conduct the qualitative analysis of plant extracts, aiming to identify various classes of secondary metabolites. Moreover,...
This study utilized phytochemical screening to conduct the qualitative analysis of plant extracts, aiming to identify various classes of secondary metabolites. Moreover, the antibacterial activity of different types of and extracts was determined. To achieve the aim of this study, aqueous, ethanolic, and enzymatic extracts were prepared and screened for phytochemical capacity and antioxidant activities. The determination of the antibacterial activity included phenotypic screening of antibiotic susceptibility pattern of oral and food pathogenic bacterial strains, determination of the minimum inhibitory concentration and minimum bactericidal concentration-via microdilution broth test and in vitro valuation of antibacterial efficacies-of the anti-biofilm properties of the studied herbal extractions. Results: Our study evaluated the phytochemical composition and the antioxidant, antibacterial, and anti-biofilm properties of and extracts. The analyzed samples contained bioactive compounds, such as phenolics and flavonoids, contributing to the observed strong antioxidant effect. Furthermore, they exhibited notable activity against oral biofilm formation and demonstrated significant antibacterial efficacy against dental caries' microorganisms as well as food pathogens. Despite methodological variations, all extracts showed significant antioxidant capacity and promising antibacterial activity against various pathogens, including resistant strains, while also inhibiting biofilm formation. Although limited to two plant species and facing methodological constraints, this study lays the groundwork for future research, indicating the therapeutic potential of and extracts. Further exploration is needed to report on underlying mechanisms and validate efficacy through clinical trials.
Topics: Origanum; Salvia; Plant Extracts; Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Antioxidants; Dental Caries; Phytochemicals; Bacteria; Humans; Food Microbiology; Flavonoids
PubMed: 38927023
DOI: 10.3390/biom14060619 -
BMC Microbiology Jun 2024Multi-drug-resistant Staphylococcus aureus infections necessitate novel antibiotic development. D-3263, a transient receptor potential melastatin member 8 (TRPM8)...
Multi-drug-resistant Staphylococcus aureus infections necessitate novel antibiotic development. D-3263, a transient receptor potential melastatin member 8 (TRPM8) agonist, has potential antineoplastic properties. Here, we reported the antibacterial and antibiofilm activities of D-3263. Minimum inhibitory concentrations (MICs) against S. aureus, Enterococcus faecalis and E. faecium were ≤ 50 µM. D-3263 exhibited bactericidal effects against clinical methicillin-resistant S. aureus (MRSA) and E. faecalis strains at 4× MIC. Subinhibitory D-3263 concentrations effectively inhibited S. aureus and E. faecalis biofilms, with higher concentrations also clearing mature biofilms. Proteomic analysis revealed differential expression of 29 proteins under 1/2 × MIC D-3263, influencing amino acid biosynthesis and carbohydrate metabolism. Additionally, D-3263 enhanced membrane permeability of S. aureus and E. faecalis. Bacterial membrane phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) dose-dependently increased D-3263 MICs. Overall, our data suggested that D-3263 exhibited potent antibacterial and antibiofilm activities against S. aureus by targeting the cell membrane.
Topics: Biofilms; Anti-Bacterial Agents; Microbial Sensitivity Tests; Staphylococcus aureus; Enterococcus faecalis; Methicillin-Resistant Staphylococcus aureus; Bacterial Proteins; Proteomics; Humans; Cell Membrane; Cell Membrane Permeability
PubMed: 38926818
DOI: 10.1186/s12866-024-03377-3 -
Korean Journal of Orthodontics Jun 2024The clinical application of aligners is accompanied by the ageing of the polymer appliances and the attachments used, which may result in inefficiency in reaching the... (Review)
Review
The clinical application of aligners is accompanied by the ageing of the polymer appliances and the attachments used, which may result in inefficiency in reaching the predicted range of tooth movement, and release of compounds and microplastics in the oral cavity as a result of the friction, wear and attrition of the aligner and composite attachment. The purpose of this review is to present the mechanism and effects of ageing; describe the hydrolytic degradation of aligners and enzymatic degradation of composite attachments; examine the ageing pattern of aligners , under actual clinical scenarios; and identify a link to the discrepancy between predicted and actual clinical outcome. Lastly, strategies to deal with three potentially critical issues associated with the use of aligners, namely the necessity of weekly renewal, the dissimilar mechanical properties of aligner and attachment resulting in wear and plastic deformation of the aligner, and the development of integuments and biofilms with microbial colonization of the appliance, are discussed.
PubMed: 38926752
DOI: 10.4041/kjod24.085 -
European Respiratory Review : An... Apr 2024Lower respiratory tract infections (LRTIs) present a significant global health burden, exacerbated by the rise in antimicrobial resistance (AMR). The persistence and... (Review)
Review
Lower respiratory tract infections (LRTIs) present a significant global health burden, exacerbated by the rise in antimicrobial resistance (AMR). The persistence and evolution of multidrug-resistant bacteria intensifies the urgency for alternative treatments. This review explores bacteriophage (phage) therapy as an innovative solution to combat bacterial LRTIs. Phages, abundant in nature, demonstrate specificity towards bacteria, minimal eukaryotic toxicity, and the ability to penetrate and disrupt bacterial biofilms, offering a targeted approach to infection control. The article synthesises evidence from systematic literature reviews spanning 2000-2023, and studies, case reports and ongoing clinical trials. It highlights the synergistic potential of phage therapy with antibiotics, the immunophage synergy in animal models, and the pharmacodynamics and pharmacokinetics critical for clinical application. Despite promising results, the article acknowledges that phage therapy is at a nascent stage in clinical settings, the challenges of phage-resistant bacteria, and the lack of comprehensive cost-effectiveness studies. It stresses the need for further research to optimise phage therapy protocols and navigate the complexities of phage-host interactions, particularly in vulnerable populations such as the elderly and immunocompromised. We call for regulatory adjustments to facilitate the exploration of the long-term effects of phage therapy, aiming to incorporate this old-yet-new therapy into mainstream clinical practice to tackle the looming AMR crisis.
Topics: Humans; Phage Therapy; Respiratory Tract Infections; Animals; Anti-Bacterial Agents; Bacteriophages; Treatment Outcome; Bacterial Infections; Bacteria; Host-Pathogen Interactions
PubMed: 38925791
DOI: 10.1183/16000617.0029-2024