Search Results (1,126)

Cancer and infectious diseases are major causes of global morbidity and mortality stressing the need to find novel drugs with promising dual anticancer and antimicrobial efficacy. Gold complexes have been studied for the past years due to their anticancer properties, with a few of them displaying antimicrobial properties, which support their pharmacological interest. Within this scope, we investigated six gold bisdithiolate complexes [Au (bdt)₂]⁻ (1), [Au (dcbdt)₂]⁻ (2), [Au (3-cbdt)₂]⁻ (3), [Au (4-cbdt)₂]⁻ (4), [Au (pdt)₂]⁻ (5) and [Au (dcdmp)₂]⁻ (6), and) against the ovarian cancer cell lines A2780 and A2780cisR, the Gram-positive bacteria Staphylococcus aureus Newman, the Gram-negative bacteria Escherichia coli ATCC25922 and Burkholderia contaminans IST408, and the pathogenic yeasts Candida glabrata CBS138 and Candida albicans SC5134. Complexes 2 and 6, with ligands containing aromatic pyrazine or phenyl rings, substituted with two cyanonitrile groups, showed after 24 h of incubation high anticancer activities against A2780 ovarian cancer cells (IC₅₀~5 µM), being also able to overcome cisplatin resistance in A2780cisR cells. Both complexes induced the formation of ROS, activated caspase-3/7, and induced necrosis (LDH release) in a dose-dependent way, in a greater extent in the case of 6. Among the bacterial and fungal strains tested, only complex 6 presented antimicrobial activity against S. aureus Newman, indicating that this complex is a potential novel anticancer and antibacterial agent. These results delve into the structure-activity relationship of the complexes, considering molecular alterations such as replacing a phenyl group for a pyrazine group, and the inclusion of one or two cyanonitrile appendage groups, and their effects on biological activity. Overall, both complexes were found to be promising leads for the development of future anticancer drugs against low sensitive or cisplatin resistant tumors. Full article

The demand for wild animal meat, popularly called “bushmeat”, serves as a driving force behind the emergence of infectious diseases, potentially transmitting a variety of pathogenic bacteria to humans through handling and consumption. This study investigated the microbial load and bacterial diversity in bushmeat sourced from a prominent bushmeat market in Kumasi, Ghana. Carcasses of 61 wild animals, including rodents (44), antelopes (14), and African civets (3), were sampled for microbiological analysis. These samples encompassed meat, intestines, and anal and oral swabs. The total aerobic bacteria plate count (TPC), Enterobacteriaceae count (EBC), and fungal counts were determined. Bacterial identification was conducted using MALDI-TOF biotyping. Fungal counts were the highest across all animal groups, with African civets having 11.8 ± 0.3 log₁₀ CFU/g and 11.9 ± 0.2 log₁₀ CFU/g in intestinal and meat samples, respectively. The highest total plate count (TPC) was observed in rodents, both in their intestines (10.9 ± 1.0 log₁₀ CFU/g) and meat (10.9 ± 1.9 log₁₀ CFU/g). In contrast, antelopes exhibited the lowest counts across all categories, particularly in EBC from intestinal samples (6.1 ± 1.5 log₁₀ CFU/g) and meat samples (5.6 ± 1.2 log₁₀ CFU/g). A comprehensive analysis yielded 524 bacterial isolates belonging to 20 genera, with Escherichia coli (18.1%) and Klebsiella spp. (15.5%) representing the most prevalent species. Notably, the detection of substantial microbial contamination in bushmeat underscores the imperative for a holistic One Health approach to enhance product quality and mitigate risks associated with its handling and consumption. Full article

Mycoplasmas are known respiratory pathogens in tortoises, but few studies exist in snakes. To better understand the correlation with clinical signs and co-infections, samples from mycoplasma-positive snakes with and without clinical respiratory disease were analyzed. Oral swabs from 15 snakes (pythons n = 12, boas n = 3) were examined using polymerase chain reaction (PCR) and third-generation sequencing (TGS). Additionally, mycoplasma isolation assays were performed. Pathogens detected by PCR included Mycoplasmas (15/15, 100%), serpentoviruses (9/15, 60%), and Chlamydia sp. (2/15, 13%); those detected by TGS included Mycoplasmas (14/15, 93%), serpentoviruses (10/15, 67%), Chlamydia sp. (1/15, 7%), and 15 different bacterial species. Sequencing of the mycoplasma PCR products revealed a close genetic relationship to Mycoplasmopsis agassizii. TGS identified genetically distinct mycoplasmas and three different serpentoviruses. While mycoplasmas could not be successfully propagated, Brucella intermedia comb. nov. was identified in eight cultures. Respiratory disease in snakes is often multifactorial, involving various pathogens and environmental influences. This study demonstrates that comprehensive diagnostics are essential for understanding disease processes in snakes and improving the detection of diverse pathogens. Further research is needed to improve laboratory diagnostics for infectious diseases in reptiles and to better understand the roles of various pathogens in respiratory diseases in snakes. Full article

Background: Infectious proctitis remains an underrecognized entity, although sexually transmitted diseases, especially bacterial infections, exhibit a marked increase in their incidence. Methods: Here, we report a case of a 44-year-old man who presented to the emergency department with lower abdominal and rectal pain, tenesmus, fever and night sweats for the past 6 days. Results: The computed tomography initially revealed a high suspicion of metastatic rectal cancer. The endoscopic findings showed a 5 cm rectal mass, suggestive of malignancy. The histologic examination showed, however, no signs of malignancy and lacked the classical features of an inflammatory bowel disease, so an infectious proctitis was further suspected. The patient reported to have had unprotected receptive anal intercourse, was tested positive for Treponema pallidum serology and received three doses of intramuscular benzathine penicillin G. A control rectosigmoidoscopy, imaging at 3 months and histological evaluation after antibiotic treatment showed a complete resolution of inflammation. Conclusions: Syphilitic proctitis may mimic various conditions such as rectal cancer or inflammatory bowel disease and requires a high degree of suspicion. Clinicians need to be aware of infectious proctitis in high-risk populations, while an appropriate thorough medical history may guide the initial diagnostic steps. 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

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article

Background: The objective of this study is to investigate the prevalence and epidemiological changes of major sexually transmitted infections (STIs) in Korea over the past decade. Methods: From 2010 to 2021, patients diagnosed with STIs based on ICD-10 codes were analyzed using Korean Health insurance data. The analysis included the number of patients, prevalence, and age-specific prevalence (in 5-year intervals) over this period. We examined changes in disease patterns over time by analyzing the annual trends and age-specific prevalence of bacterial STIs such as chlamydia, mycoplasma, gonorrhea, and syphilis; viral STIs such as genital herpes, human papillomavirus (HPV), and human immunodeficiency virus (HIV); and other infections including scabies, pubic lice, and trichomoniasis. Results: In 2010, the STI with the highest prevalence due to an infectious pathogen was trichomoniasis (256.65/100,000), while latent syphilis had the lowest prevalence (5.29/100,000). In 2021, the STI with the highest prevalence was genital herpes (254.54 per 100,000 persons), and latent syphilis continued to have the lowest prevalence. Bacterial STIs showed a decreasing trend. Viral STIs showed a continuous increase throughout the study period, with anogenital warts (AGW) having the highest rate of increase. Other infections showed a decreasing trend. HIV and AGW in men showed a rapid increase. Gender differences varied depending on the disease. Conclusions: While bacterial STIs have gradually declined, viral STIs have continued to increase during last decade. The characteristics of each pathogen vary according to age and gender, necessitating the establishment of risk groups for each pathogen and the development of prevention policies accordingly. Full article

The rapid and accurate detection of pathogenic bacteria and viruses is critical for infectious disease control and public health protection. While conventional methods (e.g., culture, microscopy, serology, and PCR) are widely used, they are often limited by lengthy processing times, high costs, and specialized equipment requirements. In recent years, metal nanocluster (MNC)-based biosensors have emerged as powerful diagnostic platforms due to their unique optical, catalytic, and electrochemical properties. This systematic review comprehensively surveys advancements in MNC-based biosensors for bacterial and viral pathogen detection, focusing on optical (colorimetric and fluorescence) and electrochemical platforms. Three key aspects are emphasized: (1) detection mechanisms, (2) nanocluster types and properties, and (3) applications in clinical diagnostics, environmental monitoring, and food safety. The literature demonstrates that MNC-based biosensors provide high sensitivity, specificity, portability, and cost-efficiency. Moreover, the integration of nanotechnology with biosensing platforms enables real-time and point-of-care diagnostics. This review also discusses the limitations and future directions of the technology, emphasizing the need for enhanced stability, multiplex detection capability, and clinical validation. The findings offer valuable insights for developing next-generation biosensors with improved functionality and broader applicability in microbial diagnostics. Full article

Cancer remains one of the leading causes of death globally, highlighting the urgent need for novel anticancer therapies with higher efficacy and reduced toxicity. Similarly, the rise in multidrug-resistant pathogens and emerging infectious diseases underscores the critical demand for new antimicrobial agents that target resistant infections through unique mechanisms. This study used computational approaches to investigate twenty quinolone–triazole and conazole–triazole hybrid derivatives as antimicrobial and anticancer agents (1–20) with nine reference drugs. By studying their interactions with 6 bacterial DNA gyrase and 10 cancer-inducing target proteins (E. faecalis, M. tuberculosis, S. aureus, E. coli, M. smegmatis, P. aeruginosa and EGFR, MPO, VEGFR, CDK6, MMP1, Bcl-2, LSD1, HDAC6, Aromatase, ALOX15) and comparing them with established drugs such as ampicillin, cefatrizine, fluconazole, gemcitabine, itraconazole, ribavirin, rufinamide, streptomycin, and tazobactam, compounds 15 and 16 emerged as noteworthy antimicrobial and anticancer agents, respectively. In molecular dynamics simulations, compounds 15 and 16 had the strongest binding at −10.6 kcal mol⁻¹ and −12.0 kcal mol⁻¹ with the crucial 5CDQ and 2Z3Y proteins, respectively, exceeded drug-likeness criteria, and displayed extraordinary stability within the enzyme’s pocket over varied temperatures (300–320 K). In addition, we used density functional theory (DFT) to calculate dipole moments and molecular orbital characteristics and analyze the thermodynamic stability of putative antimicrobial and anticancer derivatives. This finding reveals a well-defined, possibly therapeutic relationship, supported by theoretical and future in vitro and in vivo studies. Compounds 15 and 16, thus, emerged as intriguing contenders in the fight against infectious diseases and cancer. Full article

This study reports an improved diastereoselective synthesis of substituted spiro[chromane-2,4′-pyrimidin]-2′(3′H)-ones via the acid-catalyzed condensation of 6-styryl-4-aryldihydropyrimidin-2-ones with resorcinol, 2-methylresorcinol, and pyrogallol. The optimized method allows for the isolation of diastereomerically pure products, with stereoselectivity controlled by varying acid catalysts (e.g., methanesulfonic acid vs. toluenesulfonic acid) and solvent conditions. The synthesized compounds were evaluated for antimicrobial and antioxidant activities. Notably, the (2S*,4R*,6′R*)-diastereomers exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains with minimal inhibition concentration down to 2 µg/mL, while derivatives containing vicinal bisphenol moieties demonstrated potent antioxidant activity, with IC₅₀ values (12.5 µg/mL) comparable to ascorbic acid. Pharmacokinetic analysis of selected hit compounds revealed favorable drug-like properties, including high gastrointestinal absorption and blood-brain barrier permeability. These findings highlight the potential of spirochromane-pyrimidine hybrids as promising candidates for further development in the treatment of infectious diseases and oxidative stress-related pathologies. Full article

The escalating threat of infectious diseases necessitates the development of diagnostic technologies that are not only rapid and sensitive but also deployable at the point of care. Electrochemical impedance spectroscopy (EIS) has emerged as a leading technique for the label-free detection of pathogens, offering a unique combination of sensitivity, non-invasiveness, and adaptability. This review provides a comprehensive overview of the design and application of EIS-based biosensors tailored for pathogen detection, focusing on critical components such as biorecognition elements, electrode materials, nanomaterial integration, and surface immobilization strategies. Special emphasis is placed on the mechanisms of signal generation under Faradaic and non-Faradaic modes and how these underpin performance characteristics such as the limit of detection, specificity, and response time. The application spectrum spans bacterial, viral, fungal, and parasitic pathogens, with case studies highlighting detection in complex matrices such as blood, saliva, food, and environmental water. Furthermore, integration with microfluidics and point-of-care systems is explored as a pathway toward real-world deployment. Emerging strategies for multiplexed detection and the utilization of novel nanomaterials underscore the dynamic evolution of the field. Key challenges—including non-specific binding, matrix effects, the inherently low ΔR_ct/decade sensitivity of impedance transduction, and long-term stability—are critically evaluated alongside recent breakthroughs. This synthesis aims to support the future development of robust, scalable, and user-friendly EIS-based pathogen biosensors with the potential to transform diagnostics across healthcare, food safety, and environmental monitoring. Full article

The transmission of infectious diseases via the use of public restrooms has been previously documented. The goal of this study was to compare bacterial contamination in public vs. household restrooms and, using quantitative microbial risk assessment (QMRA), to assess the probability of infection from fomite contact with selected high-touch sites within the restrooms. Fomite surfaces in four public and four household restrooms were sampled over a period of two months. The public restrooms were in an office building occupied by 80 individuals and were considered moderate usage. The toilet seat, toilet flush handle, countertops, and floor were sampled for heterotrophic, coliform, and Escherichia coli bacteria. The highest numbers of heterotrophic bacteria and coliforms were detected on the countertops, followed by the floor. The greatest numbers of E. coli were recovered from the countertops in the household restroom, but the greatest numbers in the public restroom were recovered from the toilet flush handle. Numbers of heterotrophic bacteria and coliforms were 10 to 100 times greater in household restrooms than in public restrooms. The QMRA suggested that the greatest risk of acquiring a norovirus infection involved the touching of the countertops in household restrooms and the toilet flush handles in public restrooms. Full article

Fungal prosthetic joint infection (fPJI) is one of the orthopaedic pathologies where there is no clear evidence, guidelines or algorithm to guide the surgeon in its management. This is in addition to the difficulty with which these infections are diagnosed, isolated and treated. Fungi form notorious biofilms that are difficult to eradicate once formed and that display resistance to antimicrobial agents. These biofilms have been shown to act synergistically with biofilms of bacteria, further adding to medical treatment resistance. We have reviewed the literature for reports that describe the results of different methods in surgically treating fPJI. We found that surgical management with two stages remains the gold standard for treatment of fPJI, as is the case for bacterial PJI (bPJI). We have investigated medical treatment, debridement with implant retention (DAIR) and staged revisions and whether a reasonable recommendation can be made based on the best knowledge and practice available. From the data on bPJI, there exists a role for conservative management of acute PJI with debridement, antibiotics and implant retention (DAIR). While fPJI and bPJI both represent infections, the differences in our ability to detect these infections clinically, culture the pathogens and treat them with proper antimicrobial agents, along with the difference in the reported results of the surgical treatment, make us believe that these two types of infections should not be treated in the same manner. With all this in mind, we reviewed several reports in the literature on fPJI to determine the efficacy of current treatment modalities, including DAIR, which followed current guidelines for PJI. Data show an overall treatment success rate of 64.4% [range 17.4–100%]. Subgroup analysis revealed a success rate of 11.6% [range 0–28.7%] in patients treated with DAIR. There is no doubt that DAIR should not be encouraged as it consistently has a bad record. Although there are not enough studies or numbers of patients to show an evidence-based preference over one- or two-staged revisions, the two-stage revision of fPJI consistently shows better results and should be considered as the gold standard of management in cases of revision fPJI. This should also be coupled with proper expertise, follow-ups and recommended lengths of medical treatment, which should not be less than six months. From the review of these data, we have developed reasonable recommendations for the management of fPJI. These recommendations center on staged surgical debridement along with medical management. Medical treatment should be for at least 6 months under the guidance of an infectious disease team and based on intraoperative cultures. In the case of local antimicrobial treatment reported in the literature, many patients with fPJI were found to have a polymicrobial infection. As a result, it is our recommendation that antifungals as well as antibacterials should be incorporated into the cement spacer mix of these cases. Fungal PJI remains an exceedingly difficult pathology to treat and should be managed by experienced surgeons in a well-equipped institution. Full article

Prion diseases are classically attributed to the accumulation of protease-resistant prion protein (PrP^Sc); however, recent evidence suggests that alternative misfolded prion conformers and systemic inflammatory factors may also contribute to neurodegeneration. This study investigated whether recombinant moPrP^Res, generated by incubating wild-type mouse PrP^C with bacterial lipopolysaccharide (LPS), can induce prion-like disease in FVB/N female mice, whether LPS alone causes neurodegeneration, and how LPS modulates disease progression in mice inoculated with the Rocky Mountain Laboratory (RML) strain of prions. Wild-type female FVB/N mice were randomized into six subcutaneous treatment groups: saline, LPS, moPrP^Res, moPrP^Res + LPS, RML, and RML + LPS. Animals were monitored longitudinally for survival, body weight, and clinical signs. Brain tissues were analyzed histologically and immunohistochemically for vacuolar degeneration, PrP^Sc accumulation, reactive astrogliosis, and amyloid-β plaque deposition. Recombinant moPrP^Res induced a progressive spongiform encephalopathy characterized by widespread vacuolation and astrogliosis, yet with no detectable PrP^Sc by Western blot or immunohistochemistry. LPS alone triggered a distinct neurodegenerative phenotype, including cerebellar amyloid-β plaque accumulation and terminal-stage spongiosis, with approximately 40% mortality by the end of the study. Co-administration of moPrP^Res and LPS resulted in variable regional pathology and intermediate survival (50% at 750 days post-inoculation). Interestingly, RML + LPS co-treatment led to earlier clinical onset and mortality compared to RML alone; however, vacuolation levels were not significantly elevated and, in some brain regions, were reduced. These results demonstrate that chronic endotoxemia and non-infectious misfolded PrP conformers can independently or synergistically induce key neuropathological hallmarks of prion disease, even in the absence of classical PrP^Sc. Targeting inflammatory signaling and toxic prion intermediates may offer novel therapeutic strategies for prion and prion-like disorders. Full article

Background: Bacterial resistance to antimicrobial drugs is a critical phenomenon that is hampering clinical treatments, raising the need for promising compounds that can be explored as pharmaceutical products. This study investigated the antimicrobial potential of α-Ag₂WO₄–alpha phase, orthorhombic structure silver tungstate nanoparticles (STN), against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, alone and combined to clinically relevant antimicrobial drugs. Methods: We used classical methods (MIC/checkerboard) to investigate the antimicrobial activity of STN. We characterized STN using X-ray diffraction, photoluminescence and scanning electron microscopy. We also performed cytotoxicity tests on BGM cells and anti-inflammatory tests in vitro. Results: STN was effective at 128 µg/mL for S. aureus and at 256 µg/mL for E. coli, but was not effective against P. aeruginosa. When combined with antimicrobials, STN decreased their MIC values, and its anti-inflammatory potential was confirmed. CC₅₀ of STN was of 16.23 ± 1.09 μg/mL against BGM cells. Conclusions: Our data open doors for further studies in animal models to investigate the effects on STN in infectious diseases. Full article