Search Results (128)

Background: Burkholderia pseudomallei, the causative agent of melioidosis, infects diverse animal species and reflects environmental contamination. However, the global seroprevalence of B. pseudomallei in animals remains incompletely characterized. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261306404). PubMed, Embase, and Scopus were searched for observational studies reporting seroprevalence of B. pseudomallei in animals. Random-effects meta-analysis was performed to estimate the pooled prevalence with 95% confidence intervals (CIs). Subgroup analyses were conducted by animal group, geographic region, diagnostic method, and indirect hemagglutination assay (IHA) cut-off value. Risk of bias was assessed using the Joanna Briggs Institute checklist. Results: Twenty studies involving 78,914 animals were included. The pooled seroprevalence of B. pseudomallei was 11% (95% CI: 6–19%), with substantial heterogeneity (I² = 98.1%, p < 0.0001). Wildlife showed the highest prevalence (16%; 95% CI: 10–25%), followed by livestock (11%; 95% CI: 6–19%). Significant geographic variation was observed (p < 0.0001), with higher prevalence reported in North America (18%) and Southeast Asia (10%). Seroprevalence estimates varied according to diagnostic method and IHA cut-off values. Sensitivity analyses yielded similar pooled prevalence estimates after exclusion of small studies, supporting the stability of the overall findings despite persistent heterogeneity. Conclusions: Exposure to B. pseudomallei is widespread among animal populations and influenced by geographic and methodological factors. Standardized diagnostic approaches and expanded animal surveillance are needed to improve understanding of melioidosis epidemiology within a One Health framework. Full article

Mucormycosis is a devastating invasive fungal infection primarily caused by Mucor and Rhizopus species, presenting significant clinical challenges due to limited therapeutic options and emerging drug resistance in opportunistic yeasts such as Candida albicans. This study explores foliar endophytic fungi from Thai medicinal plants as potential reservoirs for novel bioactive metabolites targeting both fungal growth and virulence factors. We report the first isolation of Fusarium proliferatum as an endophyte from Lantana camara L. foliage (voucher number 01562), with its identity confirmed through morphological characterization and sequencing of the fungal ITS4/ITS5 regions. Antifungal susceptibility testing showed potent activity against a panel of environmental Mucorales, with minimum inhibitory concentrations (MICs) ranging from 0.3 to 1 mg/L. In dual-culture assays, F. proliferatum demonstrated significant mycelial inhibition rates of 93.30% to 93.67% against Mucor spp. and 88.67% to 93.67% against Rhizopus spp. Furthermore, the crude extract exhibited a potent anti-virulence effect by suppressing the C. albicans yeast-to-hyphal transition, achieving up to 68% germination inhibition in resistant strains. Liquid chromatography–mass spectrometry (LC-MS) analysis identified 51 secondary metabolites, including the cyclic peptide beauvericin and various polyketides and indole derivatives. These findings suggest that F. proliferatum utilizes metabolic mimicry and adaptive synergy with its host plant to produce a diverse chemical arsenal. This study positions foliar endophytes of L. camara as promising candidates for the development of dual-action therapeutics to combat invasive and resistant mycoses. Full article

Background/Objectives: Kaposi’s sarcoma (KS) is an angioproliferative malignancy caused by Kaposi’s sarcoma-associated herpesvirus (KSHV), characterized by aberrant angiogenesis, chronic inflammation, and endothelial cell transformation. Given the multi-factorial nature of KS pathogenesis, strategies that simultaneously modulate multiple mo-lecular targets are considered more promising than single-target approaches. However, effective multi-target therapeutic agents for KS remain limited, prompting this study to employ an integrative in silico pipeline. Methods: An integrative in silico pipeline combining compound screening, target predic-tion, network pharmacology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Ge-nomes (KEGG) enrichment, protein–protein interaction (PPI) analysis, molecular docking, and molecular dynamics (MD) simulations was employed. Streptomyces-derived metabolites were prioritized based on chemical diversity, annotation, and clinical prece-dent. Predicted targets were intersected with KS-associated genes, with hubs ranked by network topology. Docking and MD simulations evaluated binding affinity and stability. Results: Endostemonine I emerged as the top candidate, engaging nine of ten hub proteins, including EGFR, mTOR, PTGS2, SRC, PARP1, PPARγ, MAPK1, MAPK14, and ICAM1. Key nodes such as mTOR, PTGS2, PPARγ, and MAPK14 are central to KS-related an-gi-ogenesis, inflammation, and viral oncogenesis. GO and KEGG analyses revealed en-richment in kinase activity, cell adhesion, and PI3K–Akt/mTOR and MAPK signaling pathways. Docking indicated strong binding to mTOR, PTGS2, PARP1, PPARγ, and MAPK14, while MD simulations confirmed stable interactions for mTOR, PTGS2, PPARγ, and MAPK14. Conclusions: Collectively, these proteins represent high-confidence, druggable KS targets, with Endostemonine I as a promising multi-target scaffold. These findings highlight the therapeutic potential of Endostemonine I and warrant further validation through future in vitro and in vivo studies. Full article

Campylobacter is the primary bacterial cause of foodborne gastroenteritis globally. While international standards recommend a tiered approach for detection, emerging evidence suggests that selective protocols may introduce species-specific recovery biases. This systematic review and meta-analysis evaluated the diagnostic performance of established culture-based detection protocols across diverse food matrices. Following PRISMA 2020 guidelines, we searched multiple databases for studies reporting 2 × 2 diagnostic accuracy data through October 2024. Ten studies comprising 43 method comparisons and 4599 samples met the inclusion criteria. The overall pooled sensitivity was 95.8% (95% CI: 93.6–97.4%), and the specificity was 90.2% (95% CI: 86.8–92.9%). Even with a limited number of comparisons (n = 2), direct culture demonstrated high diagnostic sensitivity (99.1%) and significantly faster turnaround times. Crucially, selective enrichment exhibited a profound species-specific bias: C. jejuni showed 59.4 percent lower recovery than C. coli in Bolton broth, likely due to differential polymyxin B susceptibility. These findings highlight the importance of context-dependent method selection within the ISO 10272-1:2017 framework, suggesting that direct culture (Procedure C) should be prioritized for high-contamination matrices to ensure unbiased recovery of C. jejuni. Large-scale multicenter validation is warranted to confirm these exploratory findings for direct culture. Full article

Background/Objectives: Melioidosis, caused by Burkholderia pseudomallei, is a severe tropical infectious disease associated with high mortality in endemic regions. Early diagnosis remains challenging because conventional diagnostic methods, including culture, serological assays, and molecular techniques, have limitations in sensitivity, specificity, processing time, and accessibility in resource-limited settings. This review evaluates current diagnostic approaches and highlights the potential of short peptide biomarkers for improving melioidosis detection. Methods: A narrative literature review was conducted using four electronic databases (PubMed, Scopus, Web of Science, and Google Scholar) covering publications from 2000 to 2024. Relevant studies were identified using predefined keywords related to melioidosis diagnostics, biomarkers, and peptide-based approaches, and were screened based on relevance to diagnostic methods and peptide biomarker development in Burkholderia pseudomallei. Results: Several biomarkers have been investigated for melioidosis diagnostics, including capsular polysaccharide (CPS), type III secretion system 1 (TTS1), and other virulence-associated proteins such as Hcp1 and BPSS1187. Among these, CPS and TTS1 are highly conserved and specific targets widely used in molecular and antigen-based detection methods. Short peptide epitopes derived from these antigens demonstrate promising advantages over whole proteins, including improved stability, high specificity, easier synthesis, and reduced production costs. Advances in epitope prediction technologies and peptide-based biosensors have further expanded the potential applications of short peptides in rapid diagnostic platforms, including ELISA, lateral flow immunoassays, and biosensor-based detection systems. Conclusions: Short peptide–based biomarkers represent a promising strategy for developing rapid, sensitive, and cost-effective diagnostic tools for melioidosis, particularly in endemic and resource-limited settings. Full article

Background: The early diagnosis of pulmonary tuberculosis (PTB) remains a global challenge. While serum adenosine deaminase (ADA) has been associated with tuberculosis-related immune activation, its consistency across different regions and laboratory methods remains unclear. This study aims to evaluate group-level differences in serum ADA levels and identify factors influencing these variations. Methods: A systematic search was conducted across PubMed, Embase, and Scopus up to February 2026. A meta-analysis using a random-effects model was performed to calculate the pooled standardized mean difference (SMD), reflecting group-level differences in serum ADA levels between PTB patients and control groups. Results: Thirty-four studies were included. Serum ADA levels were significantly higher in PTB patients compared to healthy controls (SMD = 3.15, 95% CI: [2.51–3.79], p < 0.0001) and other respiratory diseases (SMD = 2.06, 95% CI: [1.38–2.74], p < 0.0001). Subgroup analyses revealed that geographical region and ADA measurement methods did not significantly account for the observed high heterogeneity (I² > 95%), indicating that ADA elevation was consistently observed across studies. Conclusions: Serum ADA levels were significantly elevated in patients with PTB, indicating a consistent biological association with disease status. However, given the high heterogeneity and the absence of diagnostic accuracy measures (e.g., sensitivity and specificity), these findings should not be interpreted as evidence of clinical diagnostic performance. Further diagnostic test accuracy studies are required to establish its clinical utility. Full article

Background: Procalcitonin (PCT) is a biomarker of bacterial infection and sepsis severity, but its role in melioidosis remains unclear. This study aimed to synthesize available evidence on serum PCT levels in culture-confirmed melioidosis and explore associations with disease severity and mortality. Methods: We conducted a systematic review following PRISMA guidelines and registered the protocol with PROSPERO (CRD420251166979). PubMed, Embase, and Scopus were searched up to 30 October 2025. Observational studies reporting serum PCT levels in microbiologically confirmed melioidosis were included. Study quality was assessed using the Newcastle–Ottawa Scale (NOS) for observational studies. Random-effects models were used to calculate pooled mean PCT levels, with heterogeneity assessed by I². Sensitivity analyses were performed to explore the influence of historical and small-sample studies. Results: Seven studies comprising 284 patients with culture-confirmed melioidosis were included. The pooled mean PCT level was 14.46 ng/mL (95% CI: 4.59–24.33), with substantial heterogeneity (I² = 87.7%). Sensitivity analyses excluding the oldest study and the smallest sample size reduced heterogeneity but retained consistently elevated PCT levels across cohorts. Higher PCT concentrations were consistently observed among patients with septic shock, bacteremia, and fatal outcomes, although variability in definitions precluded quantitative synthesis of prognostic effect sizes. These findings were based on heterogeneous study-level comparisons and could not be synthesized quantitatively. Conclusions: PCT is markedly elevated in melioidosis and reflects the severity of systemic infection, supporting its potential role as an adjunctive biomarker for early risk stratification. However, substantial heterogeneity and limited sample sizes prevent the establishment of a melioidosis-specific prognostic threshold. Standardized, prospective, multicenter studies are required to clarify the independent prognostic value of PCT in melioidosis management. This study establishes a pooled estimate of serum PCT levels in melioidosis and demonstrates that these values are comparable to those observed in severe bacterial sepsis, supporting its interpretation as a marker of systemic inflammatory burden rather than a disease-specific biomarker. Full article

Burkholderia pseudomallei, the causative agent of melioidosis, presents significant challenges in both treatment and environmental decontamination. Bacteriophages, or phages, are increasingly being explored as potential diagnostic, therapeutic, and biocontrol agents against this bacterial pathogen. Our recent investigation has shown that most B. pseudomallei genomes contained prophage(s) associated with specific tRNA gene loci, prompting us to explore these detectable prophages as sources of temperate phages for further applications. Transcriptomic profiling of B. pseudomallei Bp82, a model strain that possesses three different prophages, revealed high expression levels of the integrase and certain transcriptional regulatory genes within its prophages during normal exponential growth. Using one of its temperate phages, namely φBP82.2, a P2-like phage, as a model, we investigated the lysogenic–lytic control mechanisms. Mutagenesis of the integrase gene, phiBP82.2_gp51, did not improve killing activity compared to the wildtype phage. In contrast, deletion of phiBP82.2_gp38, a putative transcriptional regulatory gene, and two downstream hypothetical protein genes, phiBP82.2_gp36 and phiBP82.2_gp37, resulted in significant lytic improvement. We conclude that these genes play a crucial role in the lysogenic–lytic switch of φBP82.2, suggesting a new avenue for engineering temperate phages for future applications. Full article

Burkholderia pseudomallei is a saprophytic environmental bacterium and the causative agent of melioidosis, a serious opportunistic infection in tropical regions, including northern Australia. Infection occurs following environmental exposure via percutaneous inoculation, ingestion, or inhalation; however, the environmental reservoirs and transmission pathways responsible for human disease remain poorly defined. Groundwater has been implicated as a potential source of infection, but the factors influencing the persistence and mobility of B. pseudomallei in surface waters in North Queensland are not well understood. Water samples were collected from a groundwater-connected seasonal creek in Townsville, North Queensland, over a 12-month period encompassing wet and dry seasons. Samples were cultured on Ashdown agar and confirmed as B. pseudomallei by qPCR. Multi-locus sequence typing (MLST) was performed using targeted allele sequencing on the Oxford Nanopore MinION platform. Eighteen of 59 water samples were culture-positive for B. pseudomallei. Detection occurred exclusively in turbid, flowing water following ≥30 mm of rainfall and was observed in both wet and dry seasons. MLST of 48 isolates identified 18 sequence types, including 12 novel types. Six sequence types matched previously reported Townsville clinical isolates. These findings indicate that groundwater from a connected urban creek may function as a mobile reservoir for clinically relevant B. pseudomallei strains under specific hydrological and climatic conditions, highlighting rainfall-driven processes as key drivers of environmental exposure risk. Full article

Background: Melioidosis is a potentially fatal infectious disease caused by Burkholderia pseudomallei and is highly prevalent in tropical regions. Diabetes mellitus (DM) is the most common comorbidity among patients with melioidosis and is a well-established risk factor for acquiring the infection. However, the impact of diabetes on disease severity and mortality remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies to evaluate the association between diabetes mellitus and severe clinical outcomes in patients with melioidosis. PubMed, Embase, and Scopus were searched from database inception to 6 January 2026. Outcomes of interest included bacteremia, septic shock, intensive care unit (ICU) admission, and mortality. Pooled odds ratios with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed using the I² statistic. The review was registered in PROSPERO (CRD420251237028). Results: Twelve studies comprising patients from Southeast Asia, Australia, and South Asia were included. Diabetes prevalence among patients with melioidosis ranged from 31% to 76%. Meta-analysis showed no significant association between diabetes mellitus and bacteremia (OR 1.48, 95% CI 0.97–2.27), ICU admission (OR 1.31, 95% CI 0.43–3.99), septic shock (OR 0.67, 95% CI 0.39–1.16), or mortality (OR 0.82, 95% CI 0.66–1.03). Subgroup analysis revealed lower mortality among patients with diabetes in Southeast Asia (OR 0.74, 95% CI 0.61–0.91), while no significant association was observed in Australia. Heterogeneity varied across outcomes and regions. Conclusions: Although diabetes mellitus is a major risk factor for acquiring melioidosis, our findings suggest that it is not consistently associated with increased disease severity or mortality once infection occurs. These results should be interpreted cautiously given the limited number of included studies, heterogeneity across outcomes, and potential residual confounding. Further prospective studies are required to better define the underlying biological and healthcare-related mechanisms. Full article

Background: Alcohol is associated with increased mortality and morbidity globally. Pulmonary infections with opportunistic pathogens can occur in healthy humans; however, binge alcohol intoxication (≥0.08% BAC) is a major risk factor. We have previously shown that a single dose of alcohol comparable to binge alcohol intoxication increases infection by reducing alveolar macrophage function in vivo. Sulforaphane (SFN), a phytonutrient, is a potent inducer of antioxidant production through the induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of the nuclear factor kappa-light-chain-enhancer (NF-kB) pathway. The aim of this study was to test the therapeutic potential of SFN given as a pretreatment to prevent alcohol-induced phagocytic dysfunction. Methods: Intracellular phagocytic killing was measured via colony-forming units (CFU) and cytokine expression via ELISA. G. mellonella survival was used to determine the therapeutic potential of SFN in vivo. Results: Dose–response curves indicated that SFN concentrations of less than 20 µM were not cytotoxic in either MH-S (murine) or THP-1 (human) cells. Live infection assay results showed that MH-S and THP-1 cells pretreated with SFN (5 µM) and challenged with 0.2% (v/v) alcohol for 3 or 8 h prior to live B. thailandensis or S. epidermidis infection improved intracellular pathogen killing between 12- and 20-fold compared to macrophages treated with alcohol alone. ELISA analysis indicated that SFN significantly reduced levels of Tumor necrosis factor-alpha (TNF-α) expression at 3 and 8 h compared to controls. Additionally, a Galleria mellonella larvae model demonstrated greater survivability in the prophylaxis group compared to larvae exposed to either Gram-positive or Gram-negative pathogens, as well as in groups that received alcohol prior to pathogen inoculation. Conclusions: Taken together, SFN-induced cytoprotection was extended beyond in vitro cell culture to include an in vivo G. mellonella model demonstrating protection against Gram-positive and negative opportunistic pathogens. These data demonstrate that SFN may be an effective pretreatment option to prevent alcohol-mediated innate immune dysfunction and restore macrophage phagocytic killing. Full article

Melioidosis is increasingly recognised in tropical and subtropical regions worldwide as a serious and potentially fatal bacterial infection affecting humans and animals, acquired from the environment. Until now, human cases of melioidosis had not been reported in Southern Africa. Over a four-year period, we identified three human and two animal cases of melioidosis in South Africa and Namibia. Burkholderia pseudomallei isolates were investigated by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and whole-genome sequencing (WGS). Phylogenetic analysis demonstrated substantial diversity, suggesting long-term cryptic persistence of the bacterium in the Southern African region. Limited awareness of the disease and inadequate diagnostic capacity likely contribute to its apparent rarity in the region. These findings underscore the urgent need for increased surveillance, improved diagnostics, and greater awareness of melioidosis in Southern Africa to better understand its true epidemiological burden and prevent future cases. Full article

Background: Melioidosis, caused by Burkholderia pseudomallei, is a severe and often underdiagnosed infection endemic to South Asia, Southeast Asia, and northern Australia. While pneumonia and sepsis are the classical presentations, the disease is increasingly recognized for its diverse and atypical clinical manifestations. Objective: The objective is to improve diagnostic accuracy and increase clinical awareness in both endemic and non-endemic settings by reviewing and classifying atypical presentations of melioidosis that have been documented in the literature. Methods: A narrative, case-based review was conducted using 238 published case reports and series from endemic and transitional regions during the period from 2000 to 2025. Cases with non-respiratory presentations or anatomical locations not commonly linked to melioidosis were classified as atypical. Clinical syndromes were used to classify the extracted cases, and common patterns in presentation, diagnosis, and outcome were examined. Results: One hundred and sixty published articles were included after a full text review. The most frequent atypical presentations included neurological involvement (e.g., brain abscess, encephalomyelitis), musculoskeletal infections (osteomyelitis, myositis), thyroid abscess, tubo-ovarian abscess, and dermatologic manifestations such as erythema nodosum. Imported and pediatric cases were also found. Numerous cases were misidentified as cancer, fungal infections, or tuberculosis. Among risk factors, diabetes mellitus was the most prevalent. Non-specific symptoms, a lack of laboratory capacity, and incorrect pathogen identification frequently resulted in delays in diagnosis. Conclusions: In endemic areas, melioidosis should be taken into account when making a differential diagnosis of a variety of clinical syndromes, especially in patients who have diabetes or have had relevant environmental exposure. Poor outcomes and diagnostic delays are greatly exacerbated by atypical presentations. Improving diagnostic capabilities and raising awareness are crucial to lessening the worldwide burden of this often ignored but potentially deadly infection. Full article

Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in Sarawak, Malaysian Borneo, where it is represented by a unique gentamicin-susceptible population. Despite trimethoprim-sulfamethoxazole (co-trimoxazole) being the cornerstone of eradication therapy, emerging reports of elevated minimum inhibitory concentrations (MICs) among Sarawak isolates have raised concerns over its clinical efficacy. We performed a retrospective and comprehensive antibiotic susceptibility assessment of clinical B. pseudomallei isolates from hospitals across Sarawak. Susceptibility to trimethoprim-sulfamethoxazole was determined using disk diffusion and the E-test, interpreted by both CLSI and EUCAST guidelines. Resistance to the individual components, trimethoprim and sulfamethoxazole, was characterized by broth microdilution. The results demonstrated a high prevalence of trimethoprim-sulfamethoxazole susceptibility, with 96.3% of isolates susceptible by CLSI criteria and 97.6% by EUCAST criteria. Interestingly, broth microdilution revealed that resistance to trimethoprim and sulfamethoxazole individually did not confer resistance to the synergistic combination. Our analysis validated CLSI guidelines as the most reliable standard for antimicrobial resistance surveillance in this region. This study provides evidence that trimethoprim-sulfamethoxazole remains effective for melioidosis treatment in Sarawak, offering crucial reassurance to clinicians. The paradoxical finding of susceptibility to the drug combination despite resistance to its individual components underscores the critical importance of the synergistic activity of trimethoprim-sulfamethoxazole and highlights the need for further investigation into the molecular basis of resistance in this distinct B. pseudomallei population. Full article

Burkholderia pseudomallei complex and B. cepacia complex are two evolutionary distinct clades of pathogens causing human disease. Most vaccine efforts have focused on the former group largely due to their biothreat status and global disease burden. It has been proposed that a vaccine could be developed that simultaneously protects against both groups of Burkholderia by specifically targeting conserved antigens. Only a few studies have set out to identify which antigens may be optimal targets for such a vaccine. We have previously assessed the ability of three highly conserved B. pseudomallei antigens, namely OmpA1, OmpA2, and Pal, coupled to gold nanoparticle vaccines, to protect mice against a homotypic B. pseudomallei challenge. Here, we have expanded our study by demonstrating that antibodies to each of these proteins show varying levels of reactivity to homologues in B. cepacia complex, with OmpA2 antibodies exhibiting the highest cross-reactivity. Remarkably, some nanovaccine immunized mice, particularly those that received OmpA2, produced antibodies that bind Pseudomonas aeruginosa, which harbors distantly related homologous proteins. T cells elicited to Pal and OmpA2 responded to stimulation with B. cepacia complex-derived homologues. Our study supports incorporation of these antigens, particularly OmpA2, for the development of a pan-Burkholderia vaccine. Full article