Search Results (13,557)

The Mycoplasmataceae are a family of bacteria that typically cause respiratory, arthritic, and genitourinary disease in humans. Mycoplasma spp. of animal origin are also the causative agents of porcine wheezing disease, chronic respiratory disease and arthritis in chickens and other conditions. These diseases have a significant impact on public health and the economic development of livestock breeding. Clinical prevention and treatment of mycoplasma infections is primarily dependent on the use of antibiotics. However, inappropriate and excessive use of antimicrobials has enabled resistance development that has become a significant clinical concern. Mycoplasma are also robust biofilm producers, and this process is a major factor for the persistence of these infections, especially in conjunction with common antibiotic resistance mechanisms, including target gene mutations and the action of efflux pumps. A mycoplasma biofilm refers to a structured and stable microbial community formed by Mycoplasma spp. adhering to biological or non-biological surfaces under suitable conditions and secreting extracellular polymers (EPS) such as polysaccharides. This process allows the microorganisms to adapt to their surrounding environment and survive during the growth process. These biofilms render bacteria more resistant to antimicrobials than planktonic bacteria, resulting in biofilm-associated infections that are more challenging to eradicate and more likely to recur. The current study reviews progress from the fields of biofilm formation, structure and identification, correlations between biofilms and drug resistance and virulence as well as methods of biofilm prevention and control. Our aim was to provide a reference basis for the subsequent in-depth understanding of the research of mycoplasma biofilms. Full article

Combining antibiotics with propolis is an effective method to combat bacterial drug resistance. Nanoparticles are of interest in the antimicrobial field because of their higher drug stability, solubility, penetration power, and treatment efficacy. In this study, propolis nanoparticles (PNPs) were synthesized, and their antibacterial and anti-biofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) in combination with ampicillin sodium (AS) were analyzed. The PNPs had an average particle diameter of 118.0 nm, a polydispersity index of 0.129, and a zeta potential of −28.2 mV. The fractional inhibitory concentration indices of PNPs and AS against tested MRSA strains highlighted this synergy, ranging between 0.375 and 0.5. Crystal violet staining showed that combined PNPs and AS significantly inhibited biofilm formation and reduced existing biofilm biomass. We then discovered that PNPs inhibited bacterial adhesion, extracellular polysaccharide synthesis, and mecR1, mecA, blaZ, and icaADBC gene expression. These results indicated that PNPs exerted a synergistic antibacterial effect with AS by inhibiting mecR1, mecA, and blaZ gene expressions to reduce the drug resistance of MRSA. Meanwhile, PNPs weakened bacterial adhesion and aggregation by suppressing icaADBC gene expression, allowing antibiotics to penetrate the biofilm, and exhibiting significant synergistic anti-biofilm activity. In summary, PNPs are promising candidates for combating MRSA-related diseases. Full article

The global rise in antimicrobial resistance poses a major threat to public health, with multidrug-resistant bacterial infections expected to surpass cancer in mortality by 2050. As traditional antibiotic pipelines stagnate, novel therapeutic alternatives are critically needed. Antimicrobial peptides (AMPs), particularly those derived from marine organisms, have emerged as promising antimicrobial candidates due to their broad-spectrum activity, structural diversity, and distinctive mechanisms of action. Unlike conventional antibiotics, AMPs can disrupt microbial membranes, inhibit biofilm formation, and even modulate immune responses, making them highly effective against resistant bacteria. This review highlights the potential of marine AMPs as next-generation therapeutics, emphasizing their efficacy against multidrug-resistant pathogens and biofilm-associated infections. Furthermore, marine AMPs show promise in combating persister cells and disrupting quorum sensing pathways, offering new strategies for tackling chronic infections. Despite their potential, challenges such as production scalability and limited clinical validation remain; nevertheless, the use of new technologies and bioinformatic tools is accelerating the discovery and optimization of these peptides, paving the way for bypassing these challenges. This review consolidates current findings on marine AMPs, advocating for their continued exploration as viable tools in the fight against antimicrobial resistance. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Pseudomonas aeruginosa poses significant health threats due to its multidrug-resistant profile, particularly affecting immunocompromised individuals. The pathogen’s ability to produce virulence factors and antibiotic-resistant biofilms, orchestrated through quorum-sensing (QS) mechanisms, complicates conventional therapeutic interventions. This review aims to critically assess the potential of anti-QS strategies as alternatives to antibiotics against P. aeruginosa infections. Comprehensive literature searches were conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies addressing QS inhibition strategies published recently. Anti-QS strategies significantly attenuate bacterial virulence by disrupting QS-regulated genes involved in biofilm formation, motility, toxin secretion, and immune evasion. These interventions reduce the selective pressure for resistance and enhance antibiotic efficacy when used in combination therapies. Despite promising outcomes, practical application faces challenges, including specificity of inhibitors, pharmacokinetic limitations, potential cytotoxicity, and bacterial adaptability leading to resistance. Future perspectives should focus on multi-target QS inhibitors, advanced delivery systems, rigorous preclinical validations, and clinical translation frameworks. Addressing current limitations through multidisciplinary research can lead to clinically viable QS-targeted therapies, offering sustainable alternatives to traditional antibiotics and effectively managing antibiotic resistance. Full article

Widespread antibiotic residues are accumulating in the environment, potentially causing adverse effects for humans, animals, and the ecosystem, including an increase in antibiotic-resistant bacteria, resulting in worldwide concern. There are various commonly used physical, chemical, and biological treatments for the degradation of antibiotics. However, the elimination of toxic end products generated by physicochemical methods and the need for industrial applications pose significant challenges. Hence, environmentally sustainable, green, and readily available approaches for the transformation and degradation of these antibiotic compounds are being sought. Herein, we review the impact of sustainable fungal laccase-based bioremediation strategies. Fungal laccase enzyme is considered one of the most active enzymes for biotransformation and biodegradation of antibiotic residue in vitro. For industrial applications, the low laccase yields in natural and genetically modified hosts may constitute a bottleneck. Methods to screen for high-laccase-producing sources, optimizing cultivation conditions, and identifying key genes and metabolites involved in extracellular laccase activity are reviewed. These include advanced transcriptomics, proteomics, and metagenomics technologies, as well as diverse laccase-immobilization technologies with different inert carrier/support materials improving enzyme performance whilst shifting from experimental assays to in situ monitoring of residual toxicity. Still, more basic and applied research on laccase-mediated bioremediation of pharmaceuticals, especially antibiotics that are recalcitrant and prevalent, is needed. Full article

Antibiotic resistance is considered to be one of the most complex health obstacles of our time. Methicillin-resistant Staphylococcus aureus (MRSA) represents a global health challenge due to its broad treatment resistance capacity, resulting in high mortality rates. The shikimate pathway (SP) is responsible for the biosynthesis of chorismate from glycolysis and pentose phosphate pathway intermediates. This pathway plays a crucial role in producing aromatic amino acids, folates, ubiquinone, and other secondary metabolites in bacteria. Notably, SP is absent in humans, which makes it a specific and potential therapeutic target to explore for discovering new antibiotics against MRSA. The present study characterized in vitro and in silico natural products as inhibitors of the shikimate dehydrogenase from methicillin-resistant S. aureus (SaSDH). The results showed that, from the set of compounds studied, phloridzin, rutin, and caffeic acid were the most potent inhibitors of SaSDH, with IC₅₀ values of 140, 160, and 240 µM, respectively. Furthermore, phloridzin showed a mixed-type inhibition mechanism, whilst rutin and caffeic acid showed non-competitive mechanisms. The structural characterization of the SaSDH–inhibitor complex indicated that these compounds interacted with amino acids from the catalytic site and formed stable complexes. In biological activity studies against MRSA, caffeic acid showed an MIC of 2.2 mg/mL. Taken together, these data encourage using these compounds as a starting point for developing new antibiotics based on natural products against MRSA. Full article

Antibiotic misuse accelerates resistance dissemination via plasmid conjugation, but quorum sensing (QS) regulatory mechanisms remain undefined. Using Escherichia coli (E. coli) MG1655 conjugation models (RP4-7/EC600 plasmids), we demonstrate that long-chain acyl-homoserine lactones (C10/C12-HSL) enhance transfer frequency by up to 7.7-fold (200 μM C12-HSL; p < 0.001), while quorum-quenching by sub-inhibitory vanillin suppressed this effect by 95% (p < 0.0001). C12-HSL compromised membrane integrity via ompF upregulation (4-fold; p < 0.01) and conjugative pore assembly (trbBp upregulated by 1.38-fold; p < 0.05), coinciding with ROS accumulation (1.5-fold; p < 0.0001) and SOS response activation (recA upregulated by 1.68-fold; p < 0.001). Crucially, rpoS and rmf deletion mutants reduced conjugation by 65.5% and 55.8%, respectively (p < 0.001), exhibiting attenuated membrane permeability (≤65.5% reduced NPN influx; p < 0.0001), suppressed ROS (≤54% downregulated; p < 0.0001), and abolished transcriptional induction of conjugation/stress genes. Reciprocal RpoS–RMF (ribosomal hibernation factor) crosstalk was essential for AHL responsiveness, with deletions mutually suppressing expression (≤65.9% downregulated; p < 0.05). We establish a hierarchical mechanism wherein long-chain AHLs drive resistance dissemination through integrated membrane restructuring, stress adaptation, and RpoS–RMF-mediated genetic plasticity, positioning QS signaling as a viable target for curbing resistance spread. Full article

Bee products, in particular honey, propolis and bee venom, are of growing scientific interest due to their broad spectrum of antimicrobial activity. In the face of increasing antibiotic resistance and the limitations of conventional therapies, natural bee-derived substances offer a promising alternative or support for the treatment of infections. This paper summarizes the current state of knowledge on the chemical composition, biological properties and antimicrobial activity of key bee products. The main mechanisms of action of honey, propolis and bee venom are presented, and their potential applications in the prevention and treatment of bacterial, viral and fungal infections are discussed. Data on their synergy with conventional drugs and prospects for use in medicine and pharmacology are also included. The available findings suggest that, with appropriate standardization and further preclinical and clinical analyses, bee products could become an effective support for the treatment of infections, especially those caused by pathogens resistant to standard therapies. Full article

Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article

Antibiotic-resistant Pseudomonas aeruginosa presents a critical global health challenge, particularly in hospital-acquired infections. Bacteriophages offer a promising therapeutic avenue due to their ability to target and lyse resistant strains. This study characterizes Pseudomonas phage Banzai, a newly isolated Pbunavirus (family Lindbergviridae) with lytic activity against multiple P. aeruginosa isolates, including multidrug-resistant strains. Genomic analysis revealed a 66,189 bp genome, lacking antibiotic resistance or virulence factors, and suggested a headful packaging mechanism and the presence of a bidirectional component in the replication. In vivo experiments using Galleria mellonella showed therapeutic potential, significantly improving larval survival (87% at 24 h). Host range analysis revealed activity against 13 of 30 P. aeruginosa isolates, including members of O1, O3, O5 and O6 in silico predicted serogroups. Phylogenomic analyses place phage Banzai within the genus Pbunavirus, sharing 94.8% intergenomic similarity with its closest relatives, supporting its classification as a novel species. These findings highlight phage Banzai as a potential candidate for phage therapy, demonstrating genomic stability, a strictly lytic lifestyle, and in vivo efficacy. Full article

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the food chain, thereby diminishing the efficacy of antibiotics in treating bacterial infections. Current research explores the potential of essential oils from derived medicinal plants as alternative phytobiotics. This review examines modern encapsulation strategies that incorporate essential oils into natural-origin matrices to improve their stability and control their release both in vitro and in vivo. We discuss a range of encapsulation approaches utilizing polysaccharides, gums, proteins, and lipid-based carriers. This review highlights the increasing demand for antibiotic alternatives in animal nutrition driven by regulatory restrictions, and the potential benefits of essential oils in enhancing feed palatability and stabilizing the intestinal microbiome in monogastric animals and ruminants. Additionally, we address the economic viability and encapsulation efficiency of different matrix formulations. Full article

Biofilms are structured communities of microorganisms encased in a self-produced extracellular matrix, and they represent one of the most widespread forms of microbial life on Earth. Their presence poses serious challenges in both environmental and clinical settings. In natural and industrial systems, biofilms contribute to water contamination, pipeline corrosion, and biofouling. Clinically, biofilm-associated infections are responsible for approximately 80% of all microbial infections, including endocarditis, osteomyelitis, cystic fibrosis, and chronic sinusitis. A particularly critical concern is their colonization of medical devices, where biofilms can lead to chronic infections, implant failure, and increased mortality. Implantable devices, such as orthopedic implants, cardiac pacemakers, cochlear implants, urinary catheters, and hernia meshes, are highly susceptible to microbial attachment and biofilm development. These infections are often recalcitrant to conventional antibiotics and frequently necessitate surgical revision. In the United States, over 500,000 biofilm-related implant infections occur annually, with prosthetic joint infections alone projected to incur revision surgery costs exceeding USD 500 million per year—a figure expected to rise to USD 1.62 billion by 2030. To address these challenges, surface modification of medical devices has emerged as a promising strategy to prevent bacterial adhesion and biofilm formation. This review focuses on recent advances in chemical surface functionalization using non-antibiotic agents, such as enzymes, chelating agents, quorum sensing quenching factors, biosurfactants, oxidizing compounds and nanoparticles, designed to enhance antifouling and mature biofilm eradication properties. These approaches aim not only to prevent device-associated infections but also to reduce dependence on antibiotics and mitigate the development of antimicrobial resistance. Full article