Search Results (461)

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

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

Enterococcus spp. are opportunistic and nosocomial pathogens. Intensive pig farms have been recently described as important hotspots for antibiotic resistance and reservoirs of potentially pathogenic enterococci, including other species than the most known E. faecalis and E. faecium. Here, we identified Linezolid-resistant non-E. faecalis and E. faecium (NFF) Enterococcus strains isolated from different production stages (suckling piglets, weaning pigs, and fatteners) across six intensive pig farms. The transferability of the linezolid-resistance determinants was assessed by bacterial conjugation and strains were also characterized for biofilm production, hemolytic and gelatinase activity. Among 64 identified NFF Enterococcus strains, 27 were resistant to at least three different antibiotic classes and 8/27 specifically to Linezolid. E. gallinarum and E. casseliflavus both transferred their Linezolid resistance determinants to the main pathogenic species E. faecium. Remarkably, this is the first report of the optrA gene transfer from E. casseliflavus to E. faecium by conjugation, which can greatly contribute to the spread of antibiotic resistance genes among pathogenic enterococcal species. The “weaning pigs” stage exhibited a significantly higher number of antibiotic-resistant enterococci than the “fatteners”. These findings highlight the importance of monitoring pig farms as hotspots for the spread of antibiotic-resistant enterococci, especially in the early stages of production. Furthermore, they underscore the significant role of NFF Enterococcus species as carriers of antibiotic resistance genes, even to last-resort antibiotics, which may be transferable to the major enterococcal species. Full article

Genomic islands (GIs) including integrative and conjugative elements (ICEs), prophages, and integrative plasmids are central drivers of horizontal gene transfer in bacterial plant pathogens. These elements often carry cargo genes encoding virulence factors, antibiotic and metal resistance determinants, and metabolic functions that enhance environmental adaptability. In plant-pathogenic species such as Pseudomonas syringae, GIs contribute to host specificity, immune evasion, and the emergence of novel pathogenic variants. ICEclc and its homologs represent integrative and mobilizable elements whose tightly regulated excision and transfer are driven by a specialized transcriptional cascade, while ICEs in P. syringae highlight the ecological impact of cargo genes on pathogen virulence and fitness. Pathogenicity islands further modulate virulence gene expression in response to in planta stimuli. Beyond P. syringae, GIs in genera such as Erwinia, Pectobacterium, and Ralstonia underpin critical traits like toxin biosynthesis, secretion system acquisition, and topoisomerase-mediated stability. Leveraging high-throughput genomics and structural biology will be essential to dissect GI regulation and develop targeted interventions to curb disease spread. This review synthesizes the current understanding of GIs in plant-pathogenic gammaproteobacteria and outlines future research priorities for translating mechanistic insights into sustainable disease control strategies. Full article

Background/Objectives: The number needed to vaccinate (NNV) is a metric commonly used to evaluate the public health impact of a vaccine as it represents the number of individuals that must be vaccinated to prevent one case of disease. Traditional calculations may underestimate vaccine benefits by neglecting indirect effects and duration of protection (DOP), resulting in NNV overestimation. This study evaluated the NNV for the pediatric 20-valent pneumococcal conjugate (PCV20) US immunization program, as compared to PCV13, with a unique approach to NNV. Methods: A multi-cohort, population-based Markov model accounting for indirect effects was employed to calculate the NNV of PCV20 to avert a case of pneumococcal disease, invasive pneumococcal disease (IPD), hospitalized non-bacteremic pneumonia (NBP), ambulatory NBP, and otitis media (OM), as well as to prevent antibiotic-resistant cases and antibiotic prescriptions. Results: The mean NNV over a 25-year time horizon to prevent one case of pneumococcal disease was 6, with NNVs of 854 for IPD, 106 for hospitalized NBP, 25 for outpatient NBP, and 9 for OM, 11 for a course of antibiotic, and 4 for resistant disease. The mean NNV per year decreased over time, reflecting the DOP and increasing indirect effects over time. Conclusions: This study presents a novel approach to NNVs and shows that relatively few vaccinations are required to prevent disease. The decrease in NNV over time highlights the necessity of including DOP and indirect effects in NNV calculations, ensuring a more realistic assessment of a vaccine’s impact. Full article

Background/Objectives: Campylobacteriosis in human populations is an ongoing issue in both developed and developing countries. Poultry production is recognized as a reservoir for antimicrobial resistance and main source of human Campylobacter infection. Methods: In this study, sixty-five Campylobacter isolates were cultured from fecal samples collected from 17 flocks of broiler chickens in Alberta, Canada over two years (2015–2016). Susceptibility assays and PCR assays were performed to characterize resistance phenotypes and resistance genes. Conjugation assays were used to examine the mobility of AMR phenotypes. Results: Campylobacter jejuni was the predominant species recovered during both years of sampling. There were no Campylobacter coli isolates found in 2015; however, approximately 33% (8/24) of isolates collected in 2016 were Campylobacter coli. The two most frequent antimicrobial resistance patterns in C. jejuni collected in 2015 were tetracycline (39%) and azithromycin/clindamycin/erythromycin/telithromycin resistance (29%). One isolate collected in 2015 has resistance pattern ciprofloxacin/nalidixic acid/tetracycline. The tetO gene was detected in all tetracycline resistant isolates from 2015. The cmeB gene was detected in all species isolates with resistance to azithromycin/clindamycin/erythromycin/telithromycin, and from two isolates with tetracycline resistance. Alignment of the nucleotide sequences of the cmeB gene from C. jejuni isolates with different resistance patterns revealed several single nucleotide polymorphisms. A variety of multi-drug resistance patterns were observed through conjugation experiments. Conclusions: These data suggest that poultry production may serve as a potential reservoir for and source of transmission of multi-drug resistant Campylobacter jejuni and supports the need for continued surveillance. Full article

A significant issue in healthcare is the growing prevalence of antibiotic-resistant strains. Therefore, it is necessary to develop strategies for discovering new antibacterial compounds, either by identifying natural products or by designing semisynthetic or synthetic compounds with this property. In this context, a great deal of research has recently been carried out on antimicrobial peptides (AMPs), which are natural, amphipathic, low-molecular-weight molecules that act by altering the cell surface and/or interfering with cellular activities essential for life. Progress is also being made in developing strategies to enhance the activity of these compounds through their association with other molecules. In addition to identifying AMPs, it is essential to ensure that they maintain their integrity after passing through the digestive tract and exhibit adequate activity against their targets. Significant advances are being made in relation to analyzing various types of conjugates and carrier systems, such as nanoparticles, vesicles, hydrogels, and carbon nanotubes, among others. In this work, we review the current knowledge of different types of AMPs, their mechanisms of action, and strategies to improve performance. Full article

The invention of antibacterial agents (antibiotics) was a significant event in the history of the human race, and this invention changed the way in which infectious diseases were cured; as a result, many lives have been saved. Recently, antibiotic resistance has developed as a result of excessive use of antibiotics, and it has become a major threat to world health. ARGs are spread across biomes and taxa of bacteria via lateral or horizontal gene transfer (HGT), especially via conjugation, transformation, and transduction. This review concerns transduction, whereby bacteriophages or phages facilitate gene transfer in bacteria. Bacteriophages are just as common and many times more numerous than their bacterial prey, and these phages are much more influential in controlling the population of bacteria. It is estimated that 25% of overall genes of Escherichia coli have been copied by other species of bacteria due to the HGT process. Transduction may take place via a generalized or specialized mechanism, with phages being ubiquitous in nature. Phage and virus-like particle (VLP) metagenomics have uncovered the emergence of ARGs and mobile genetic elements (MGEs) of bacterial origins. These genes, when transferred to bacteria through transduction, confer resistance to antibiotics. ARGs are spread through phage-based transduction between the environment and bacteria related to people or animals, and it is vital that we further understand and tackle this mechanism in order to combat antimicrobial resistance. Full article

Developing advanced antimicrobial agents is critically imperative to address antibiotic-resistant infection crises. MXenes have emerged as a potential nanomedicine for antibacterial applications, but they suffer from suboptimal photothermal conversion efficiency and inherent cytotoxicity. Herein, we report the synthesis of MXene (Ti₃C₂)-based nanohybrids and hybrid membranes through firstly interfacial conjugation of self-assembled β-lactoglobulin nanofibers (β-LGNFs)-inspired copper sulfide nanoparticles (CuS NPs) onto MXene nanosheets, and subsequent vacuum filtration of the created β-LGNF-CuS/MXene nanohybrids. The constructed β-LGNF-CuS/MXene nanohybrids exhibit excellent photothermal conversion performances and satisfactory biocompatibility and minimal cytotoxicity toward mammalian cells, ascribing to the introduction of highly biocompatible β-LGNFs into the hybrid system. In addition, the fabricated β-LGNF-CuS/MXene hybrid membranes demonstrate high efficiency in antibacterial application through the synergistic photothermal and material-related antibacterial effects of both MXene and CuS NPs. Therefore, the ideas and findings shown in this study are useful for inspiring researchers to design and fabricate functional and biocompatible 2D material-based hybrid membranes for antimicrobial applications. Full article

Antimicrobial peptides (AMPs) represent a powerful support to conventional antibiotics in addressing the global challenge of antimicrobial resistance (AMR). Their broad-spectrum antimicrobial activity and unique mechanisms of action enable diverse potential applications, including combating multidrug-resistant pathogens, immune modulation, and cancer therapy. Their clinical implementation is hindered by challenges such as toxicity, instability, and high production costs. Recent advances in AMP design, optimization, and delivery mechanisms such as nanoparticle conjugation and rational engineering have enhanced their efficacy, stability, and specificity. Integrating AMPs into precision medicine and combining them with existing therapies promises to overcome current limitations. With ongoing advancements, AMPs have the potential to redefine infection management and possibly other medical problems. Full article

Background/Objectives: The increased use of antibiotics is raising concerns about environmental contamination and antibiotic resistance, exemplified by the case of cotrimoxazole, a widely prescribed combination of sulfamethoxazole and trimethoprim. After oral administration and absorption, both drugs are excreted in their parent and metabolized forms, which is a factor that is commonly considered in environmental studies. Many studies, however, rely on pharmacokinetic data from drug developers, who mostly investigate drug metabolism in healthy male volunteers rather than in actual patient populations. Methods: We investigated the real-world metabolism and urinary excretion of cotrimoxazole in an LC-SWATH/MS-based pharmacometabolomics study of 149 kidney transplant recipients who took part in the TransplantLines Biobank and Cohort Study (NCT0327284). Results: Our study confirmed (as “putatively characterized compound classes”) the presence of all the expected metabolites, and we (putatively) identified several previously unreported metabolites, including glucuronide conjugates of both drugs and two isoxazole ring-opened variants of sulfamethoxazole. The relative metabolite profiles furthermore indicated that the active drug trimethoprim accounted for 75% of the total signal intensity. For sulfamethoxazole, its acetylated metabolite was the main metabolite (59%), followed by the active parent drug (17%) and its glucuronide (7%). Alongside trimethoprim, these substances could serve as analytical targets for environmental cotrimoxazole monitoring, given their abundance (all three substances), activity (parent drug), and/or back-transformation potential (both conjugated metabolites). The isoxazole ring-opened variants (2–3%) may also warrant attention, considering their (presumed) absolute excreted quantities and potential pharmacological activity. Conclusions: This study underscores the value of pharmacometabolomics in elucidating real-world metabolite profiles, and it provides novel insights into cotrimoxazole metabolism and excretion, with implications for environmental and clinical monitoring. Full article

Background/Objectives: Clostridioides difficile is a “One Health” pathogen and a cause of antibiotics-associated diarrhea and pseudomembranous colitis. Mobile genetic elements (MGEs) have been documented in the genomes of clinical C. difficile strains; however, the presence of MGEs in environmental strains remains poorly characterized. Thus, the present study was conducted with the objective of identifying the prevalence of MGEs, including mobilizable transposons (MTns), conjugative transposons (CTns), plasmids, and insertion sequences, in whole genome sequences (WGSs) of environmental C. difficile isolates. Methods: The analysis of MGEs was conducted using 166 WGSs obtained from C. difficile strains isolated from various environmental sources contaminated with feces. The MGEs were identified using bioinformatic tools. Results: A total of 48.2% (80/166) of the studied genomes were identified to harbor nine transposons, including Tn916, Tn6194-like, Tn5397, Tn6215, Tn4001, Tn6073, Tn6110, Tn6107, or Tn5801-like. The majority of MTns and CTns could be found within C. difficile sequence types ST11, ST3, and ST35. The results demonstrated close genetic relatedness among the studied genomes, the array of antimicrobial resistance (AMR) genes, such as tetM, ermB, and aac(6′)-aph(2″), and the presence of CTns. Furthermore, the analysis revealed that 24.7% (41/166) of the genome sequences of isolates were associated with various predominant plasmid groups, including pCD6, pCD-ECE4-6, pCD-WTSI1-4, pCDBI1, and pCd1_3, which belonged to 16 different sequence types. Furthermore, several plasmids were identified as harboring the prophage phiCDHM19. Conclusions: The results of the current study suggest that the identified plasmids are abundant and may encode functions that are relevant to C. difficile physiology. The genomes of C. difficile strains examined contain closely related CTns, suggesting that horizontal transfer of AMR is important in this species or other bacterial species. Further research is required to ascertain the effect of these genetic elements and their transferability on the biology of C. difficile. Full article

Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack of studies on the prevalence of Streptococcus pneumoniae (S. pneumoniae) serotypes among vaccinated children. This research aimed to explore and compare the prevalence of nasopharyngeal pneumococcal carriage, serotype distribution, and antibiotic resistance patterns in healthy PCV13-vaccinated and -unvaccinated children. Methods: From August 2023 to November 2024, a multi-center, cross-sectional observational study was conducted in Tehran, Iran. This study included 204 nasopharyngeal samples collected from children aged from 18 to 59 months, involving both cases of children vaccinated with PCV13 and unvaccinated populations. S. pneumoniae was identified through a combination of culture methods and biochemical tests, confirmed by real-time PCR. Serotyping was achieved using cpsB sequencing, and the minimum inhibitory concentration method was employed to assess antibiotic resistance. Results: This study revealed similar S. pneumoniae carriage rates between PCV13-vaccinated and -unvaccinated Iranian children (20.6% vs. 21.6%). Serotypes 23F and 19F were prevalent in unvaccinated children, while 15B/15C was more prevalent in PCV13-vaccinated children. The included S. pneumoniae serotypes in PCV13 were detected more in the unvaccinated group. PCV13-vaccinated children exhibited no penicillin-resistant pneumococcal isolates, although four isolates were non-susceptible in unvaccinated children. Both groups showed substantial resistance to erythromycin and SXT. Previous respiratory infections, daycare attendance, residence in Tehran, and a history of antibiotic consumption increased the risk of pneumococcal carriage. Conclusions: PCV13 vaccination influences pneumococcal serotype distribution and antimicrobial susceptibility, although there was no significant difference regarding carriage rates between vaccinated and unvaccinated groups. These findings highlight the critical importance of vaccination in reducing invasive serotypes and antimicrobial resistance in children under five years old, emphasizing the importance of national PCV vaccination programs alongside continuous serotype surveillance. Full article

The therapeutic use of silver nanoparticles (AgNPs) has been increasing, especially in phototherapy strategies. The plasmonic properties of AgNPs have contributed to their excellent results as phototherapeutic agents, namely for photodynamic therapy (PDT), photothermal therapy (PTT), and photodynamic inactivation of microorganisms. Moreover, the capacity of these nanostructures to release silver ions (Ag⁺) and enhance the production of reactive oxygen species (ROS) has been explored in combination with light to treat several diseases. Moreover, synthesis, functionalization, and conjugation strategies with targeting agents have been widely studied to optimize selectivity and maximize the therapeutic efficacy of these nanoplatforms. In this work, we reviewed the recent advancements (2019–2024) in the use of AgNPs for phototherapy applications, with an emphasis on evaluating therapeutic efficacy and specific targeting. According to the literature, in oncology, AgNPs have been predominately employed in PTT-based strategies, demonstrating significant tumor cell death and preservation of healthy tissues, in both in vitro and in vivo studies. Concurrently, AgNP-mediated PDT has emerged as a promising approach for the eradication of bacteria and fungi, particularly those commonly associated with antibiotic resistance. The compiled data indicate that AgNPs represent an innovative and effective therapeutic alternative, with a strong potential for clinical translation, in both cancer treatment and the management of hard-to-treat infections. Full article

Global concerns about environmental pollution, poor waste management, and the rise in antimicrobial resistance due to uncontrolled antibiotic use have driven researchers to seek alternative, multifaceted solutions. Plants, animals, microorganisms, and their processing wastes serve as valuable sources of natural biopolymers and bioactive compounds. Through nanotechnology, these can be assembled into formulations with enhanced antimicrobial properties, high safety, and low toxicity. This review explores polysaccharides, including chitosan, alginate, starch, pectin, cellulose, hemicellulose, gums, carrageenan, dextran, pullulan, and hyaluronic acid, used in nanotechnology, highlighting their advantages and limitations as nanocarriers. Addressing the global urgency for alternative antimicrobials, we examined natural compounds derived from plants, microorganisms, and animals, such as phytochemicals, bacteriocins, animal antimicrobial peptides, and proteins. Focusing on their protection and retained activity, this review discusses polysaccharide-based nanoformulations with natural antimicrobials, including nanoparticles, nanoemulsions, nanocapsules, nanoplexes, and nanogels. Special emphasis is placed on strategies and formulations for the encapsulation, entrapment, and conjugation of natural compounds using polysaccharides as protective carriers and delivery systems, including a brief discussion on their future applications, prospects, and challenges in scaling up. Full article