Type 2 diabetes mellitus (T2DM) patients are at increased risk of infections, such as malignant otitis externa and rhinocerebral mucormycosis, with the urinary tract being the most affected (for example, emphysematous pyelonephritis commonly caused by Escherichia coli). Hence, this study assessed the prevalence of bacteriuria and antibiogram patterns of bacteria isolates among T2DM patients visiting the Ejisu Government Hospital in the Ashanti Region, Ghana. In this cross-sectional study, 58 patients visiting the hospital for routine healthcare were conveniently recruited after obtaining informed consent. Data on sociodemographic characteristics and medical history were obtained using pretested structured questionnaires. Mid-stream urine was collected for bacteria isolation and identification using standard bacterial culture and biochemical tests. Bacteria cultures ≥ 105 CFU/mL were considered significant bacteriuria. The antibiotic sensitivity patterns of the bacteria isolates were evaluated using the Kirby-Bauer disc diffusion method. Bacteriuria was recorded among 15.5% (9/58) of the patients, mainly those with no previous history (77.8%) and no symptoms (55.6%) of urinary tract infections (UTIs). E. coli (55.6%) and Klebsiella spp. (44.6%) were primarily isolated from the T2DM patients. All the bacteria isolates (E. coli and Klebsiella spp.) demonstrated the highest resistance to co-trimoxazole and tetracycline (55.6%) and a complete susceptibility to amikacin and levofloxacin (100%). However, 60% of the E. coli isolates and 25% of the Klebsiella isolates were multidrug resistant (MDR; resistant to at least one antibiotic agent in three or more antimicrobial categories). The study shows that T2DM patients have bacteria in their urine which are resistant to most common antibiotics, even among those with no history of UTIs; hence, routine bacterial culture and antibiotic sensitivity testing among T2DM patients is recommended for better patient management to reduce the co-morbidities of UTIs.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, posing significant challenges and economic burdens on healthcare systems. Gut microbiota metabolites have shown promise in cancer treatment, but the specific active metabolites and their key targets remain unclear. This study employed a network pharmacology-based approach to identify potent metabolites of gut microbiota and their key targets. Active metabolites produced by gut microbiota were retrieved using the database gutMGene, and targets associated with these metabolites were identified using the Swiss Target Prediction tool. HCC-related targets were obtained from the GeneCards database, and overlapping targets were selected through a Venn diagram tool. An integrated metabolites-target-pathway network was analyzed to identify active inhibitors against HCC, including p-cresol glucuronide, secoisolariciresinol, glycocholic acid, enterodiol, and citric acid. Molecular docking tests were performed to validate the findings and assess the binding affinity of the metabolites with their target proteins. The study identified AKT1, EGFR, ALB, and TNF genes as potential therapeutic targets against hepatic cancer. The metabolites, p-cresol glucuronide, secoisolariciresinol, glycocholic acid, enterodiol, and citric acid, exhibited significant binding affinity with their respective target proteins. The study also revealed multiple signaling pathways and biological processes associated with the metabolites, demonstrating their preventive effect against HCC. This research utilizes a network pharmacology-based approach to identify potent metabolites of gut microbiota and their key targets for the treatment of HCC. The findings were validated through molecular docking tests, providing a foundation for future studies on anti-HCC metabolites and their mechanisms of action. Furthermore, this study offers insights into the development of novel anti-HCC drugs utilizing gut microbiota metabolites.
Fibrinolytic agents are essential in treating thrombosis, playing a critical role in improving survival rates in cardiovascular diseases. Microbial fibrinolytic proteases have emerged as promising alternatives due to their affordability, specificity, lower toxicity, and reduced side effects. Consequently, the search for microorganisms capable of producing these enzymes has gained significant economic importance in the pharmaceutical industry. This study reports and characterizes a novel fibrinolytic enzyme produced by Penicillium citrinum CFAM 521, a strain isolated from the Amazon region. The enzyme was purified using a polyethylene glycol (PEG)-phosphate salt aqueous two-phase system (ATPS). The effects of PEG molecular weight, PEG concentration, and phosphate concentration on the protease partition coefficient (K) were evaluated through a 22 full factorial design. The enzyme exhibited both fibrinolytic and fibrinogenolytic activities. After partitioning in a two-phase system with 10% (w/w) PEG and 15% (w/w) sodium phosphate, the fibrinolytic proteases were predominantly retained in the salt-rich bottom phase (K = 0.33). The enzyme has a molecular weight of 34 kDa, with optimal pH and temperature at 9°C and 37°C, respectively. Inhibitory analysis confirmed that it is a serine protease, and its activity was enhanced by the addition of Mn2+. Notably, the enzyme exhibited no hemolytic activity. Therefore, P. citrinum CFAM 521 represents a novel source of fibrinolytic enzymes, highlighting its potential as an alternative for the development of thrombolytic agents.
The COVID-19 pandemic has intensified the issue of multidrug-resistant (MDR) infections, particularly in intensive care units (ICUs). This study documents the first known case of coinfection with two extensively drug-resistant (XDR) bacterial isolates in a critically ill patient with COVID-19 in Saudi Arabia. Both XDR isolates were recovered from blood and were resistant to all tested antimicrobial agents except colistin. Whole genome sequencing (WGS) revealed that the K. pneumoniae isolate KP-JZ107 had sequence type 11 (ST11) and core genome MLST (cgMLST 304742), while the A. baumannii isolate AB-JZ67 had ST2 and cgMLST 785. KP-JZ107 was found to possess the virulence plasmid KpVP-type-1, carbapenemase genes bla NDM and bla KPC , and numerous antimicrobial-resistant genes (ARGs). The AB-JZ67 isolate had several biofilm-related genes, including biofilm-associated protein (BAP), csuE, and pgaB, and multiple ARGs, including bla ADC-25, bla OXA-23, and bla OXA-66. Our findings suggest that the coexistence of KP-JZ107 and AB-JZ67 isolates may indicate their widespread presence in ICUs, requiring comprehensive surveillance studies across all hospitals.
Plastics are used widely in almost every field of life, but their synthetic and persistent nature makes them harmful for the environment. The aim of this research was to evaluate the degradation abilities of Aspergillus niger, Candida albicans, and Acremonium sclerotigenum on microplastics (MPs). MP pieces of 4 ± 1 mm, including polyethylene, polyethylene terephthalate, and polystyrene, were incubated with fungal inoculums for 30 days. The degradation of treated MPs was determined by biofilm formation, weight loss, scanning electron microscopy (SEM), and Fourier transform analyses. The results indicated that the polyethylene MPs treated with Aspergillus niger exhibited the highest level of biofilm formation (optical density 1.595) and percentage weight loss (16%). In the case of polyethylene terephthalate and polystyrene MPs, Acremonium sclerotigenum and co-culture showed weight loss of 6% and 10%, respectively. Candida albicans was observed to be the least effective in biodegradation analyses. SEM observation revealed the surface modifications as holes, pits, cracks, and increased roughness in treated MPs. Fourier transform infrared (FTIR) spectroscopy showed that the chemical structure of each polymer exhibited some variations. The study concluded that the fungal strains play an important role in the biodegradation of plastics and can be utilized to mitigate environmental pollution.
Toxigenic fungi are capable of producing toxic metabolites, called mycotoxins. But the presence of silent and lowly expressed genes represents the main challenge for the discovery of novel mycotoxins, especially their lesser-known forms, commonly referred to as "emerging mycotoxins." Epigenetic modifiers (EMs) are compounds that are able to alter the production of metabolites through the induction of silent biosynthetic pathways leading to an enhanced chemical diversity. The aim of this study was to assess the effects of different chemical modulators on the metabolic profiles of the well-known toxigenic fungal species, Fusarium verticillioides. Four EMs, 5-azacytidine, sodium butyrate, nicotinamide (NIC), and sodium valproate (SV), were used. Following their addition to Fusarium verticillioides cultures, the metabolic profiles were analyzed by using UHPLC-HRMS/MS under targeted and untargeted metabolomics approaches. Metabolites were putatively annotated through the use of MS-DIAL and MS-FINDER. Our results show that the treatment with SV induced the most important alteration of the secondary metabolic profile of F. verticillioides, by promoting the expression of cryptic genes. Among the 50 most discriminating metabolites across five culture conditions, 12 were fusarins or fusarin analogs. In contrast, SB and NIC had little impact on these metabolites. The study highlights SV's ability to alter gene expression by inhibiting DNA deacetylation in fungal strains. This research could have significant implications for agriculture and food industry, especially in regions facing major mycotoxin challenges.
Aims/Introduction: Phage display method is a crucial tool to find novel clinically valuable diabetes-associated autoantigens and identify known autoantigen epitopes that are associated with diabetes and could provide scientific support and guidance for the artificial construction and synthesis of Type I diabetes mellitus (T1DM) novel biomarkers. Materials and Methods: The phage display system was used for the "biopanning" of T1DM serum. Following the sequencing of the phage DNAs, the homologous sequences of the above fusion heptapeptide were further investigated by BLAST to track the origin of the polypeptide sequences. The antibody spectrum revealed new T1DM-associated epitopes and antibodies. Results: A total of 1200 phage DNA were sequenced and 9 conserved polypeptide sequences were collected. It was confirmed that the zinc transporter and islet amyloid protease were among them. The conserved polypeptide sequence 8 and another three distinctive polypeptide sequences derived from Proteus were discovered. Furthermore, we expressed recombinant proteins with homologous polypeptide sequences for the human islet amyloid polypeptide (IAPP) and polypeptide precursor human zinc transporter 8 (ZNT8). Through clinical sample detection for the serum from T1DM (n = 100) and T2DM (n = 200) patients, results demonstrate the importance and relevance of these polypeptides in the recognition and classification of various forms of diabetes. Conclusion: Human pancreatic and concurrent bacterial-derived protein antigens and their epitopes were identified in this research by the phage display system, which is crucial for distinguishing different types of diabetes.
Aflatoxins, primary foodborne mycotoxins, come from Aspergillus flavus and Aspergillus parasiticus fungi. They pose significant health risks to humans and animals, creating a major challenge in the dairy sector. The objective of this study is to evaluate the knowledge, attitudes, and practices (KAP) of dairy farmers regarding aflatoxin contamination in milk and feeds. Conducted as a cross-sectional study in Bahir Dar city between November 2019 and February 2020, this investigation randomly selected 106 dairy farms for data collection. Face-to-face interviews, facilitated by a semistructured questionnaire, were employed. Findings indicate that 59.4% of respondents displayed good knowledge, while a substantial 94.3% exhibited a favorable attitude. Intriguingly, only 1.9% implemented good practices. Notably, the educational background of dairy farmers emerged as a significant factor influencing their KAP (p < 0.05). Conversely, various sociodemographic factors did not yield a significant impact on the KAP of dairy farmers. Despite a robust knowledge base and favorable attitudes towards aflatoxin among dairy farmers, the study highlights a significant gap in the implementation of recommended practices. This finding emphasizes the necessity for increased efforts to cultivate and reinforce good practices. Collaborative initiatives involving diverse stakeholders are crucial to reducing aflatoxin contamination in the dairy industry.
Vaginal infections are a public health problem associated with serious health complications due to the exacerbated inflammation they generate. Vaginal inflammation may also occur in some noninfectious processes, such as noninfectious vaginitis and cytolytic vaginosis. Immune system cells respond to infections through various mechanisms, such as the formation of extracellular traps (ETs), which are DNA networks associated with effector proteins. Many pathogens induce ETs formation in vitro, as occurs in some natural infections. A recent report indicates that human vaginal infections in vivo generate ETs. Therefore, in this study, we aimed to identify ETs in samples from 40 donors who were diagnosed with infectious (i.e., bacterial vaginosis, candidiasis and trichomoniasis) and noninfectious (i.e., noninfectious vaginitis and cytolytic vaginosis) vaginal inflammation. We were able to observe ETs by identifying the LL-37 peptide, which is associated with DNA networks. In seven vaginal swabs from the control group (formed by 19 donors without vaginal infection symptoms), we detected at least one pathogen per sample and observed ETs; thus, these donors were considered asymptomatic. The remaining 12 donors were confirmed to be healthy, as their exudates did not present any tested pathogens, sign of inflammation or ETs. ETs in vaginal inflammatory processes can worsen inflammation but may also help control infection.