Search Results (2,379)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. 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

Canine visceral leishmaniasis (CVL) is a major zoonosis that poses a growing challenge to public health services, as successful disease management requires sensitive, specific, and rapid diagnostic methods capable of identifying infected animals even at a subclinical level. The objective of this study was to evaluate the performance of the recombinant chimeric protein rMELEISH3 as an antigen in ELISA assays for the robust diagnosis of CVL. The protein was expressed in a bacterial system, purified by affinity chromatography, and evaluated through a series of serological assays using serum samples from dogs infected with Leishmania infantum. ROC curve analysis revealed a diagnostic sensitivity of 96.4%, a specificity of 100%, and an area under the curve of 0.996, indicating excellent discriminatory power. Furthermore, rMELEISH3 was recognized by antibodies present in the serum of dogs with low parasite loads, reinforcing the diagnostic potential of the assay in asymptomatic cases. It is concluded that the use of the recombinant antigen rMELEISH3 could significantly contribute to the improvement of CVL surveillance and control programs in endemic areas of Brazil and other countries, by offering a safe, reproducible and effective alternative to the methods currently recommended for the serological diagnosis of the disease. Full article

Biofilms are a spontaneously formed slimy matrix of extracellular polymeric substances (EPS) enveloping miniature bacterial colonies, which aid in pathogen colonization, shielding the bacteria from antibiotics, as well as imparting them resistance towards the same. Biofilms employ a robust communication mechanism called quorum sensing that serves to keep their population density constant. What is most significant about biofilms is that they contribute to the development of bacterial virulence by providing protection to pathogenic species, allowing them to colonize the host, and also inhibiting the activities of antimicrobials on them. They grow on animate surfaces (such as on teeth and intestinal mucosa, etc.) and inanimate objects (like catheters, contact lenses, pacemakers, endotracheal devices, intrauterine devices, and stents, etc.) alike. It has been reported that as much as 80% of human infections involve biofilms. Serious implications of biofilms include the necessity of greater concentrations of antibiotics to treat common human infections, even contributing to antimicrobial resistance (AMR), since bacteria embedded within biofilms are protected from the action of potential antibiotics. This review explores various contemporary strategies for controlling biofilms, focusing on their modes of action, mechanisms of drug resistance, and innovative approaches to find a solution in this regard. This review interestingly targets the extracellular polymeric matrix as a highly effective strategy to counteract the potential harm of biofilms since it plays a critical role in biofilm formation and significantly contributes to antimicrobial resistance. Full article

Phage therapy, long overshadowed by antibiotics in Western medicine, has a well-established history in some Eastern European countries and is now being revitalized as a promising strategy against antimicrobial resistance (AMR). This resurgence of phage therapy is driven by the urgent need for innovative countermeasures to AMR, which will cause an estimated 10 million deaths annually by 2050. However, the emergence of phage-resistant variants presents challenges similar to AMR, thus necessitating a deeper understanding of phage resistance mechanisms and control strategies. The highest priority must be to prevent the emergence of phage resistance. Although phage cocktails targeting multiple receptors have demonstrated a certain level of phage resistance suppression, they cannot completely suppress resistance in clinical settings. This highlights the need for strategies beyond simple resistance suppression. Notably, recent studies examining fitness trade-offs associated with phage resistance have opened new avenues in phage therapy that offer the potential of restoring antibiotic susceptibility and attenuating pathogen virulence despite phage resistance. Thus, controlling phage resistance may rely on both its suppression and strategic redirection. This review summarizes key concepts in the control of phage resistance and explores evolutionary engineering as a means of optimizing phage therapy, with a particular focus on Pseudomonas infections. Harnessing evolutionary dynamics by intentionally breaking the spontaneous evolutionary trajectories of target bacterial pathogens could potentially reshape bacterial adaptation by acquisition of phage resistance, unlocking potential in the application of phage therapy. Full article

Background: Various predisposing factors contribute to the emergence and dissemination of the multidrug-resistant (MDR) phenotype in Escherichia coli and Klebsiella pneumoniae. Understanding these factors is crucial for guiding appropriate antimicrobial therapy and infection control strategies. This study investigated the predisposing factors contributing to the MDR characteristics of E. coli and K. pneumoniae isolated in a community hospital in northeastern Thailand. Methods: This case–control study utilized retrospective data from bacterial culture, as well as demographic, clinical, and antibiotic susceptibility records collected during 5 years (January 2016–December 2020). E. coli and K. pneumoniae isolates were analyzed from various clinical samples, including blood, urine, pus, sputum, and other body fluids. Data were analyzed using descriptive statistics and univariate logistic regression. Results: In total, 660 clinical isolates were analyzed (421 E. coli and 239 K. pneumoniae). Blood was the most common source of the detection of E. coli (63.0%) and sputum was the most common source of K. pneumoniae (51.0%). The median ages of patients were 67 and 63 years for E. coli and K. pneumoniae, respectively. E. coli cases were significantly associated with prior antibiotic use (OR = 1.79, 95% CI: 1.17–2.74 p = 0.008). MDR was observed in 50.1% of E. coli and 29.7% of K. pneumoniae (p < 0.001). E. coli compared to K. pneumoniae had lower resistance to third-gen cephalosporins (64.9% versus 95.8%) and carbapenems (8.0% versus 6.9%). ICU admission was the only factor significantly associated with MDR E. coli (OR = 2.40, 95% CI: 1.11–5.20 p = 0.026). No significant differences were observed in gender, age, or comorbidities between MDR cases. Antibiotic usage patterns also differed, with E. coli more likely to receive third-gen cephalosporins compared to carbapenems (OR = 3.02, 95% CI:1.18–7.74 p = 0.021). Conclusions: The use of third-generation cephalosporin may drive MDR E. coli more than K. pneumoniae. Prior antibiotic exposure was linked to E. coli bloodstream infections, while MDR E. coli showed greater clinical severity. These findings highlighted the need for improved antibiotic stewardship in rural hospitals. Full article

Glanders is a highly contagious and often fatal zoonotic disease of equids caused by Burkholderia mallei, a pathogen of significant concern due to its potential for bioterrorism. In Brazil, glanders remains endemic, particularly among working equids in the Northeast region. Diagnostic confirmation typically involves serology, culture, and polymerase chain reaction (PCR), although false-negative PCR results have been increasingly reported. This study aimed to evaluate the diagnostic performance and analytical sensitivity of four B. mallei-specific PCR primer sets using samples from 30 seropositive equids. Microbiological cultures were obtained from various organs and swabs, followed by PCR targeting four genomic regions: fliP-IS407A(a), fliP-IS407A(b), Burk457, and Bm17. All animals were confirmed positive for B. mallei via culture, but PCR detection rates varied significantly across primer sets. The fliP-IS407A(b) primer set showed the highest sensitivity, detecting 86% of samples, while the WOAH-recommended fliP-IS407A(a) set had the lowest performance (13.4%). Analytical sensitivity assays confirmed that fliP-IS407A(b) and Bm17 primers detected DNA concentrations as low as 0.007 ng, outperforming the others. These findings suggest that certain widely used primer sets may lack sufficient sensitivity for reliable detection of B. mallei, especially in chronically infected animals with low bacterial loads. The study underscores the need for ongoing validation of molecular diagnostics to improve the detection and control of glanders in endemic regions. Full article

Triatoma pallidipennis, the main vector of Chagas disease in central Mexico, hosts a diverse and complex gut bacterial community shaped by environmental and physiological factors. To gain insight into these microbes’ dynamics, we characterised the gut bacterial communities of wild and insectary insects under different feeding and Trypanosoma cruzi infection conditions, using 16S rRNA gene sequencing. We identified 91 bacterial genera across 8 phyla, with Proteobacteria dominating most samples. Wild insects showed greater bacterial diversity, led by Acinetobacter and Pseudomonas, while insectary insects exhibited lower diversity and were dominated by Arsenophonus. The origin of the insects, whether they were reared in the insectary (laboratory) or collected from wild populations, was the principal factor structuring the gut microbiota, followed by feeding and T. cruzi infection. A stable core microbiota of 12 bacterial genera was present across all conditions, suggesting key functional roles in host physiology. Co-occurrence and functional enrichment analyses revealed that feeding and infection induced condition-specific microbial interactions and metabolic pathways. Our findings highlight the ecological plasticity of the triatomine gut microbiota and its potential role in modulating vector competence, providing a foundation for future microbiota-based control strategies. Full article

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine storms, while excessive/persistent activity in late-phase immunosuppression drives immune paralysis and secondary infection susceptibility. This review explores advances in targeting Treg immunoregulation across bacterial, viral, and fungal sepsis, where pathogenic type critically influenced the types of immunoresponses, shaping Treg heterogeneity in terms of phenotype, survival, and function. Understanding this multifaceted Treg biology offers novel therapeutic avenues, highlighting the need to decipher functional heterogeneity and develop precisely timed, pathogen-tailored immunomodulation to safely harness beneficial Treg roles while mitigating detrimental immunosuppression. Full article

This study explores the potential of biodegradable Bioglass 45S5 formulations as a dual-function approach for preventing and treating Staphylococcus aureus infections in orthopaedic surgery while addressing the growing concern of antimicrobial resistance (AMR). The research focuses on the development and characterisation of antibiotic-loaded BG45S5 formulations, assessing parameters such as drug loading efficiency, release kinetics, antimicrobial efficacy, and dissolution behaviour. Key findings indicate that the F2l-BG45S5-T-T-1.5 and F2l-BG45S5-T-V-1.5 formulations demonstrated controlled antibiotic release for up to seven days, with size distributions of D(10): 7.11 ± 0.806 µm, 4.96 ± 0.007 µm; D(50): 25.34 ± 1.730 µm, 25.20.7 ± 0.425 µm; and D(90): 53.7 ± 7.95 µm, 56.10 ± 0.579 µm, respectively. These formulations facilitated hydroxyapatite formation on their surfaces, indicative of osteogenic potential. The antimicrobial assessments revealed zones of inhibition against methicillin-susceptible Staphylococcus aureus (MSSA, ATCC-6538) measuring 20.3 ± 1.44 mm and 24.6 ± 1.32 mm, while for methicillin-resistant Staphylococcus aureus (MRSA, ATCC-43300), the inhibition zones were 21.6 ± 1.89 mm and 22 ± 0.28 mm, respectively. Time-kill assay results showed complete bacterial eradication within eight hours. Additionally, biocompatibility testing via MTT assay confirmed cell viability of >75%. In conclusion, these findings highlight the promise of antibiotic-loaded BG45S5 as a multifunctional biomaterial capable of both combating bone infections and supporting bone regeneration. These promising results suggest that in vivo studies should be undertaken to expedite these materials into clinical applications. Full article

This study elucidates how the quorum-sensing (QS) signal 3OC12-HSL exacerbates enterotoxigenic E. coli (ETEC) pathogenicity and intestinal barrier dysfunction. In vitro, 3OC12-HSL enhanced ETEC C83902 growth (66.7% CFU increase at 8 h) and dysregulated stress/growth genes (e.g., eight-fold rmf upregulation under static conditions). In synthetic gut microbiota, 3OC12-HSL selectively augmented E. coli colonization (37.6% 16S rDNA increase at 12 h). Murine studies revealed 3OC12-HSL reduced jejunal villus height (381.5 μm vs. 543.2 μm in controls), elevated serum LPS, D-lactate, and DAO, and altered microbial composition (Firmicutes/Bacteroidetes imbalance). The lactonase AiiA reversed these effects by degrading 3OC12-HSL. It abrogated bacterial growth stimulation (in vitro CFU restored to baseline), normalized microbiota diversity (Shannon index recovered to control levels), suppressed pro-inflammatory cytokines (IL-6/TNF-α reduction), and restored intestinal integrity (villus length: 472.5 μm, 20.5% increase vs. ETEC-infected mice). Our findings establish AiiA as a potent quorum-quenching agent that counteracts ETEC virulence via targeted signal inactivation, highlighting its translational value. Full article

Objectives: Burkholderia cepacia complex (Bcc), a Gram-negative organism, is a well-recognized cause of hospital outbreaks, often linked to a contaminated shared source, such as multidose medications. In this study, we report an outbreak of Bcc infections in a tertiary care hospital, associated with the intrinsic contamination of a prepared solution used in interventional radiology (IR) procedures. Additionally, we provide a detailed explanation of the interventions implemented to control and interrupt the outbreak. Methods: Records from the infection control committee from 1 January 2023 to 31 October 2024 were screened to identify cases with Bcc growth in cultured blood, urine, or respiratory samples. Clinical and laboratory data were collected in March 2025. Bacterial identification was performed using conventional methods and MALDI-TOF (Bruker Daltonics, Bremen, Germany). Controls were matched to cases by ward, date of initial growth, and duration of hospitalization. Demographic and clinical data of these patients were systematically collected and analyzed. Microbiological cultures were obtained from environmental objects of concern and certain medications. Results: A total of 82 Burkholderia species were identified. We enrolled 77 cases and 77 matched controls. The source of contamination was identified in ready-to-use intravenous medications (remifentanil and magnesium preparations) in the IR department. These preparations were compounded in advance by the team and were used repeatedly. Although the outbreak originated from contaminated IV medications used in IR, secondary transmission likely affected 28 non-IR patients via fomites, shared environments, and possible lapses in isolation precautions. The mortality rate among the cases was 16.9%. Infection with Bcc was associated with prolonged intensive care unit stays (p = 0.018) and an extended overall hospitalization duration (p < 0.001); however, it was not associated with increased mortality. The enforcement of contact precautions and comprehensive environmental decontamination successfully reduced the incidence of the Bcc outbreak. No pathogens were detected in cultures obtained after the disinfection. Conclusions: The hospital transmission of Bcc is likely driven by cross-contamination, invasive medical procedures, and the administration of contaminated medications. Implementing stringent infection control measures such as staff retraining, updated policies on medication use, enhanced environmental decontamination, and strict adherence to isolation precautions has proven effective in curbing the spread of virulent and transmissible Bcc. Full article

Increased antimicrobial resistance requires effective ways to overcome the global challenge of bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). From the emergence of MRSA to its continued evolution, it is important to explore this pathogen from fresh perspectives and develop corresponding coping strategies to counter its growing threat. New coping strategies are continuously emerging, including but not limited to enhancing penetration capabilities or targeting their virulence. This review summarizes the epidemiological characteristics, drug resistance mechanisms, and therapeutic strategies of MRSA that have emerged over the past fifteen years. The focus of this paper is to explore the promising applications and current limitations of novel MRSA control strategies. This review serves as a key resource for treating MRSA infections and discussing novel strategies to overcome bacterial drug resistance. Full article

Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in the case of antibiotic resistance. Objectives: In this study, we examined the effects of aPDT using the photosensitizers (PSs), methylene blue (MB) or Photodithazine (PDZ), both alone and in combination with the antibiotics ciprofloxacin (CIP), gentamicin (GEN), and ceftriaxone (CEF), against the Gram-negative bacterium Klebsiella pneumoniae. Methods: A standard suspension of K. pneumoniae was subjected to PDT with varying doses of MB and PDZ solutions, using a 75 mW/cm² LED emitting at 660 nm with an energy of 15 J/cm². The MICs of CIP, GEN, and CEF were determined using the broth dilution method. We also tested the photosensitizers MB or PDZ as potentiating agents for synergistic combinations with antibiotics CIP, GEN, and CEF against K. pneumoniae. Results: The results showed that MB was more effective in inhibiting survival and killing K. pneumoniae compared to PDZ. The tested antibiotics CIP, GEN, and CEF suppressed bacterial growth (as shown by reduced MIC values) and effectively killed K. pneumoniae (reduced Log CFU/mL). While antibiotic treatment or aPDT alone showed a moderate effect (1 Log₁₀ to 2 Log₁₀ CFU reduction) on killing K. pneumoniae, the combination therapy significantly increased bacterial death, resulting in a ≥3 Log₁₀ to 6 Log₁₀ CFU reduction. Conclusions: Our study indicates that pre-treating bacteria with PDT makes them more susceptible to antibiotics and could serve as an alternative for treating local infections caused by resistant bacteria or even reduce the required antibiotic dosage. This work explores numerous possible combinations of PDT and antibiotics, emphasizing their interdependence in controlling infections and the unique properties each PS-antibiotic combination offers. Clinical application for the combination is a promising reality since both are individually already adopted in clinical use. Full article

Vibrio parahaemolyticus (V. parahaemolyticus) is a preeminent seafood-borne pathogen, imposing significant economic burdens on global aquaculture. The escalating prevalence of multidrug-resistant strains has accentuated the critical urgency for developing sustainable biocontrol strategies. In this study, a bacteriophage designated vB_VPAP_XY75 (XY75) was isolated and biologically characterized to establish an effective control against V. parahaemolyticus. XY75 exhibited remarkable specificity toward V. parahaemolyticus, effectively lysing 46.2% of the target strains while showing no lytic activity against non-target bacterial species. Morphological characterization confirmed its taxonomic assignment to the Myoviridae family, featuring an icosahedral head (40 ± 2 nm) and contractile tail (60 ± 2 nm). XY75 demonstrated strong environmental tolerance, remaining stable at pH 4–11 and temperatures as high as 50 °C. At an optimal multiplicity of infection (MOI = 0.01), XY75 achieved a peak titer of 8.1 × 10¹⁰ PFU/mL, a 5 min latent period, and burst size of 118 PFU/cell. Critically, XY75 reduced V. parahaemolyticus in salmon by more than 5.98 log CFU/g (99.9%) within 6 h at 4 °C, demonstrating exceptional cold tolerance and lytic activity. Genomic analysis confirmed that no virulence or antibiotic resistance genes were present. These results establish XY75 as a safe and efficacious biocontrol candidate for seafood preservation, with particular utility under refrigerated storage conditions. Full article