Rime Bioinformatics’ Post

Innate mechanism protects bacteria from last-resort antibiotic New research has shown that bacteria have an innate mechanism that protects them from the last-resort antibiotic polymyxin. A study by Dr. Anna Lena Jung of the Deutsches Zentrum für Lungenforschung (DZL) at the Philipps-Universität Marburg, Germany, investigated the behavior of #polymyxin against the bacterium #Klebsiella #pneumoniae, which is particularly dangerous for immunocompromised patients and is increasingly resistant to conventional antibiotics. The study by PhD student Marie Burt and colleagues revealed that Klebsiella pneumoniae releases more vesicles under the influence of polymyxin. These vesicles intercept the antibiotic and prevent it from attacking the bacterial membrane. Remarkably, these vesicles protect not only the producing bacteria, but also neighboring susceptible microbes such as Pseudomonas aeruginosa. The researchers found that the dose of polymyxin that reaches the lungs is often too low to be effective because higher doses would damage the kidneys. This allows the bacteria to activate their defense mechanism, making treatment more difficult. Mass spectrometry analysis showed that under antibiotic stress, bacteria change the composition of the vesicle shell to contain less lipid A, which is normally the main target of polymyxin. The increased release of vesicles still releases enough lipid A into the environment to scavenge the antibiotic. This mechanism only occurs in Klebsiella that have been tested as polymyxin susceptible prior to treatment. Bacteria with genetic polymyxin resistance alter the gene for lipid A so that polymyxin can no longer bind. Dr. Jung emphasizes the need for further research to develop new antimicrobial peptides that do not trigger stress-induced protective mechanisms in bacteria in the face of increasing antibiotic resistance. Read more about the findings on the DZL website by following the link below. #DZL #DZG #PulmonaryResearch #LungDisease #Science #AntibioticResistance #Polymyxin #Bacteria #KlebsiellaPneumoniae #Lung #Infectiousdiseases #Antibiotics 

Specific native microbiota #Klebsiella_oxytoca may be used as a live #antibiotic against known pathobiome #Salmonella_Typhimurium and the resulting specific disease states or possibly also against other #Salmonellas (#typhoid_fever). [ Mouse/In vitro ] [ Preclinical study ] NOTES: - The Klebsiella_oxytoca species complex is part of the human microbiome, especially during infancy and childhood.  - K. oxytoca species complex strains can produce #enterotoxins, namely, #tilimycin and #tilivalline, while also contributing to colonization resistance (CR).  - K. oxytoca provides CR against Salmonella_Typhimurium. - In vitro, the antimicrobial activity against various Salmonella strains depended on tilimycin production and was induced by various simple carbohydrates. - In vivo, CR against Salmonella depended on toxin production in germ-free mice, while it was largely toxin-independent in mice with residual microbiota. - #dulcitol utilization was essential for toxin-independent CR in gnotobiotic mice.

🌍🦠 Genomic Insights into Staphylococcus aureus and Atopic Dermatitis 🧬✨ Atopic dermatitis (AD) is the most common chronic inflammatory skin disease globally, and the interplay between AD and the skin microbiota plays a crucial role in its progression. Notably, Staphylococcus aureus is more prevalent in AD patients than in healthy individuals (HE), but the strain-specific differences remain unclear. Our latest research unveils key genomic and functional distinctions between S. aureus strains from AD and HE on both global and local scales: - Global Findings: AD-associated strains have reduced gene content diversity but increased functional variation. We identified two AD-dominant clusters:    - Cluster 1: Enriched with transposases.   - Cluster 2: Containing genes linked to adaptability and antibiotic resistance. - The lantibiotic operon, crucial for biosynthesizing lantibiotics, was acquired through horizontal gene transfer from environmental bacteria. - Local Analysis: Mirrored global trends but highlighted unique functional variations, with local strains exhibiting a strong focus on metal-related genes. This study provides foundational insights into how S. aureus adapts within the AD microenvironment, with implications for understanding antibiotic resistance and guiding future clinical microbiology practices. Another great paper together with Michael Schloter . This great collaboration connects Helmholtz Munich Universität Augsburg and Universitätsklinikum Augsburg. Read more details here https://lnkd.in/d29Jfgdn #AtopicDermatitis #StaphylococcusAureus #Microbiome #Genomics #AntibioticResistance #ClinicalMicrobiology #Research

Hi everyone! I just finished reading an interesting scientific article. Each day I'll share information about research. #science #lifesciences #biology Tesfamariam M, Vij R, Trümper V, Hube B, Brunke S. 2024. Shining a light on Candida-induced epithelial damage with a luciferase reporter. mSphere9:e00509-24. https://lnkd.in/eHPsgcZF Fungal pathogens, such as 𝘊𝘢𝘯𝘥𝘪𝘥𝘢 𝘢𝘭𝘣𝘪𝘤𝘢𝘯𝘴, are a widespread public health issue due to their potential to cause severe damage to host cell systems. This study presents a cost-effective and time-efficient assay to assess the level of epithelial cell damage. The developed assay uses the NanoLuc (Nluc) luciferase reporter, which is introduced into mammalian cell lines through lentiviral transduction. The expression of the luciferase gene is then measured to indicate the severity of cell damage caused by 𝘊. 𝘢𝘭𝘣𝘪𝘤𝘢𝘯𝘴. Key findings showed that the Nluc assay was comparable to the LDH cytotoxicity assay in terms of sensitivity. Additionally, the Nluc assay overcomes temperature and pH limitations of the LDH assay. Future directions for this assay include its application in testing new antibiotics and exploring the underlying cellular mechanisms that contribute to epithelial cell damage.

The battle against Staphylococcus aureus using natural compounds from Ganoderma mushrooms Background: Staphylococcus aureus is a nosocomial pathogen responsible for many serious infectious diseases in humans. Finding the anti- S. aureus agents is a time-consuming and costly process. Recently, computational methods have provided a better understanding of the interactions between herbal medicine drug targets to help clinical practitioners rationally design herbal formulae. Methods: In this study, molecular docking simulation was applied to screen a list of natural secondary metabolites from Ganoderma sp. on the protein target S. aureus sortase A. Molecular dynamics models were used to assess the stability of protein–ligand complexes during the first 100 ns. To validate the computational results, 2 Ganoderma species, G. multiplicatum VNKKK1901 and G. sinense VNKKK1902, were tested for antibacterial activity against S. aureus using the disk diffusion method. Results: The results showed that, among the selected compounds, ganosinensin B and ganosinoside A generated the highest binding energy on S. aureus sortase A, and demonstrated strong and stable binding capacity to proteins. In addition, the extracts of G. sinense VNKKK1902 and G. multiplicatum VNKKK1901 were bactericidal, with minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) ratios of 2. Conclusion: Our findings provide the first scientific report on the antibacterial activity of Ganoderma sp., which contain 2 promising compounds, ganosinensin B and ganosinoside A, as potential hits for developing novel drugs capable of supporting treatment of S. aureus infection. https://lnkd.in/eK5Q5msn

 Phage Therapy: Phage Therapy offers a beacon of hope, with its ability to tackle global challenges such as antibiotic resistance and clean fuel production. This captivating and rapidly evolving field holds significant promise in managing the escalating issue of antibiotic-resistant bacterial infections.   Phage therapy research involves: ●      Understanding how phages interact with bacteria, ●      finding new phages ●      changing them to work better against bacteria.   Scientists are actively testing phage therapy in people, ensuring its safety and efficacy. They're also exploring innovative ways to deliver phages to patients and using phages in agriculture to combat infections in animals and plants. Furthermore, researchers are investigating how phages can dismantle biofilms, which are clusters of bacteria that are resistant to antibiotics. In essence, the aim is to conquer antibiotic resistance and establish phage therapy as a viable treatment option.   Phage therapy, a century-old practice of using bacteriophage viruses to combat bacterial infections, has a rich history. Despite gaining increasing support from researchers and doctors in the past 15 years, primarily due to the surge of antibiotic resistance, it continues to face developmental challenges. Bacteriophages, commonly known as phages, are viruses that invade bacteria, and they're everywhere bacteria are found. They're the most common biological commodities on Earth, with billions of them in ecosystems. Humans have known about phages since the early 20th century when scientists like Frederick Twort and Félix d'Hérelle first discovered them. Hérelle even isolated them from dysentery patients' feces in 1917.   While phage therapy shows promise in the treatment of bacterial infections, it is crucial to consider regulatory and material factors to enhance its accessibility and effectiveness. Continued research and development are necessary to harness its potential fully.

New Research: Bacteriophage as a novel therapeutic approach for killing multidrug-resistant Escherichia coli ST131 clone https://lnkd.in/gvHi9Vdw #FrontiersIn #Microbiology

𝗦𝗲𝗮𝗿𝗰𝗵𝗶𝗻𝗴 𝗳𝗼𝗿 𝘁𝗵𝗲 𝗺𝗶𝗰𝗿𝗼𝗯𝗶𝗮𝗹 𝘁𝗿𝗲𝗮𝘀𝘂𝗿𝗲: Most antibiotics used in human medicine originate from natural products derived from bacteria and other microbes. Novel microorganisms are therefore a promising source of new active compounds - also for the treatment of diseases such as cancer or viral infections. A team from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) has now been able to isolate a completely new family of bacteria that has particularly high potential for the production of active substances. 𝗡𝗲𝘄 𝗳𝗮𝗺𝗶𝗹𝘆 𝗼𝗳 𝗯𝗮𝗰𝘁𝗲𝗿𝗶𝗮 𝘄𝗶𝘁𝗵 𝗵𝗶𝗴𝗵 𝗽𝗵𝗮𝗿𝗺𝗮𝗰𝗲𝘂𝘁𝗶𝗰𝗮𝗹 𝗽𝗼𝘁𝗲𝗻𝘁𝗶𝗮𝗹 𝗱𝗶𝘀𝗰𝗼𝘃𝗲𝗿𝗲𝗱: https://lnkd.in/dJ-hrDa3 Chantal Bader, Johanna Löhr, Judith Boldt, Boyke B., F.P. Jake Haeckl, Thomas Pietschmann, Helmholtz-Zentrum für Infektionsforschung, Universität des Saarlandes, Susanne Thiele, Charlotte Schwenner (geb. Wermser)

🔬 **Innovative Advance in Tackling Drug-Resistant Fungal Strains** 🔬 The alarming rise of drug-resistant Candida parapsilosis poses a significant challenge for healthcare facilities worldwide. A research team led by Dr. Amelia Barber and Dr. Grit Walther has developed a breakthrough molecular detection method to identify and track resistant strains of this fungus effectively. Published in *The Lancet Microbe*, their study presents a detailed genomic analysis of a persistent outbreak across healthcare facilities in Berlin. It highlights how a single strain caused multiple invasive infections, underscoring the pathogen's global spread and significant threat due to its resistance to conventional antifungal treatments. The newly developed Multilocus Sequence Typing (MLST) offers a rapid, cost-effective alternative to whole genome sequencing, enabling swift response to outbreaks. This innovation is crucial for resource-limited centers, enhancing global efforts to curb the spread of drug-resistant fungi. #HealthcareInnovation #InfectionControl #PublicHealth #Microbiology #DrugResistance

🚀 Exciting Research Publication! 🔬 We are thrilled to share GCIR-MIT latest research on innovative solutions to combat antibiotic resistance, a growing global health threat. 🌍💊 This study reveals the potential of host-acting compounds in the fight against drug-resistant infections. They explored the effects of #bosutinib, an FDA-approved chemotherapeutic for chronic myelogenous leukemia, on enhancing the immune response to bacterial infections. 🦠 🔍 Key findings: Enhanced #macrophage activity: bosutinib stimulates murine and human macrophages to kill bacteria more effectively, despite having no direct antibiotic activity. Effective in #WoundInfections: in murine models with #vancomycin-resistant #Enterococcus faecalis wound infections, bosutinib reduced bacterial load by approximately 10-fold through intraperitoneal injection or topical application - effects dependent on macrophage presence. Mechanistic insights: - Upregulation of bacterial uptake markers: bosutinib increases the expression of Dectin-1 and CD14 on macrophages, promoting bacterial uptake and actin remodeling. - Increased reactive oxygen species: it elevates intracellular reactive oxygen species levels, enhancing bacterial killing. - NF-κB activation: bosutinib activates NF-κB, protecting infected macrophages from apoptosis. - Synergistic effects: other Src kinase inhibitors like DMAT and tirbanibulin similarly enhance macrophage bacterial clearance. Additionally, cotreatment with mitoxantrone shows an additive effect on bacterial clearance both in vitro and in vivo. 📈 Implications: Bosutinib can stimulate macrophage-mediated bacterial clearance through multiple mechanisms, offering a promising strategy to boost innate immunity and combat drug-resistant bacterial infections. 🔗 Read the full article here: https://lnkd.in/dTXV3cFN 🔗 And a summary here: https://lnkd.in/dRvZzcEJ #AntibioticResistance #InnateImmunity #Immunomodulation #Phagocytosis #SrcKinasesTargeting Authors: Professors Kimberly Kline, Faculté de médecine - UNIGE, University of Geneva & Jianzhu Chen, Massachusetts Institute of Technology. This project is a collaboration supported by the Singapore-MIT Alliance for Research & Technology Centre - Antimicrobial Resistance Interdisciplinary Group: https://lnkd.in/d3ieb2-A