Publications by authors named "Paul Cos"

Antimicrobial peptides (AMPs) constitute a chemically and structurally heterogeneous family of molecules produced by a wide range of living organisms, including plants, fish, amphibians, mammals, and insects. Their expression is particularly high in hosts frequently exposed to microorganisms, where AMPs play a key role in innate immune responses. Insects represent one of the richest natural sources of AMPs.

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Respiratory syncytial virus (RSV) remains a major global health issue. Therapeutic options are limited, but new prophylactics, all targeting the fusion (F) glycoprotein, were recently licensed. Although F sequence variation is limited, it is unclear if and how this variability translates to phenotypical differences.

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Despite global efforts, antimicrobial resistance persists. Mechanisms like heterotolerance further undermine antibiotic effectiveness. Testing > 1000 clinical strains revealed widespread heterotolerance largely missed by conventional MIC-based diagnostics.

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Background: Efficient management of drug-resistant tuberculosis relies on fast diagnostics. To accelerate phenotypic drug susceptibility testing [pDST] for Mycobacterium tuberculosis [TB], we introduce TRACeR-TB, a test that infers drug resistance from antibiotic-specific mRNA biomarkers.

Methods: To develop TRACeR-TB, target genes were first identified through RNA sequencing experiments conducted on two drug-exposed, susceptible strains for four antitubercular drugs.

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Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5-6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions.

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Mycobacterium abscessus (Mab) infections are challenging to treat due to high intrinsic drug resistance, comparable to multidrug-resistant tuberculosis. Treatments are extremely ineffective and based on a multi-drug regimen, resulting in low patient compliance. Consequently, the scientific community is urged to identify new and effective drugs to treat these infections.

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Article Synopsis
  • * This study introduces an antibacterial hydrogel coating utilizing polymyxin B (PMB) to inhibit bacterial adhesion, with thorough characterization of its properties and effectiveness against bacteria demonstrated over at least 8 days.
  • * The coating meets international cytocompatibility standards and shows potential for prolonged PMB release, laying the groundwork for future peptide-releasing formulations aimed at preventing VAP.
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Article Synopsis
  • Mab is a highly resistant pathogen that presents a serious threat to individuals with cystic fibrosis and other chronic lung diseases, comparable to multidrug-resistant tuberculosis.
  • Current treatment options involve long multidrug therapies, which are often ineffective, leading to high rates of treatment failure and mortality, highlighting the urgent need for new drug development.
  • The research focuses on creating stable double-reporter strains of Mab to streamline drug screening, allowing for efficient identification of potential treatments through high-throughput methods while maintaining the pathogen's original characteristics.
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The synthesis of an extensive series of new squaramides with high potential in treating drug-resistant tuberculosis employing the Liebeskind-Srogl cross-coupling reaction is presented. Using the protocol given and various substrates, we assessed the scope and limitations of our methodology and prepared an extensive range of desired compounds. Moreover, H NMR spectra in solution show the presence of two rotational conformers (rotamers) in special cases.

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Bacterial pneumonia greatly contributes to the disease burden and mortality of lower respiratory tract infections among all age groups and risk profiles. Therefore, laboratory modelling of bacterial pneumonia remains important for elucidating the complex host-pathogen interactions and to determine drug efficacy and toxicity. In vitro cell culture enables for the creation of high-throughput, specific disease models in a tightly controlled environment.

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Unlabelled: The World Health Organization's goal to combat tuberculosis (TB) is hindered by the emergence of anti-microbial resistance, therefore necessitating the exploration of new drug targets. Multidrug regimens are indispensable in TB therapy as they provide synergetic bactericidal effects, shorten treatment duration, and reduce the risk of resistance development. The research within our European RespiriTB consortium explores energy metabolism to identify new drug candidates that synergize with bedaquiline, with the aim of discovering more efficient combination drug regimens.

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Respiratory Syncytial Virus (RSV) poses a significant global health concern as a major cause of lower respiratory tract infections (LRTIs). Over the last few years, substantial efforts have been directed towards developing vaccines and therapeutics to combat RSV, leading to a diverse landscape of vaccine candidates. Notably, two vaccines targeting the elderly and the first maternal vaccine have recently been approved.

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Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections in the young, the elderly, and in immunodeficient patients. As such, the virus represents an important cause of morbidity and mortality worldwide. Development of monoclonal antibodies against RSV has resulted in a commercial prophylaxis, palivizumab (Synagis), and different antibodies that have improved our understanding of the structure of the viral proteins.

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Mycobacterial ATP synthase is a validated therapeutic target for combating drug-resistant tuberculosis. Inhibition of this enzyme has been featured as an efficient strategy for the development of new antimycobacterial agents against drug-resistant pathogens. In this study, we synthesised and explored two distinct series of squaric acid analogues designed to inhibit mycobacterial ATP synthase.

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As effector molecules of the innate immune system, antimicrobial peptides (AMPs) have gathered substantial interest as a potential future generation of antibiotics. Here, we demonstrate the anti- activity and lipopolysaccharide (LPS)-binding ability of HC1 and HC10, two cecropin peptides from the black soldier fly (). Both peptides are active against a wide range of strains, including drug-resistant clinical isolates.

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The investigation of natural alternatives to conventional fungicides is of imminent need. (Britton & P. Wilson) Bisse is a Cuban endemic plant species belonging to the Myrtaceae family.

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Dry eye disease (DED) is a challenge in ophthalmology. Rat models represent valuable tools to study the pathophysiology and to develop novel treatments. A major challenge in DED research is detecting multiple biomarkers in a low tear volume sample.

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The respiratory syncytial virus (RSV) represents the leading cause of viral lower respiratory tract infections (LRTI) in children worldwide and is associated with significant morbidity and mortality rates. The clinical picture of an RSV infection differs substantially between patients, and the role of viral co-infections is poorly investigated. During two consecutive winter seasons from October 2018 until February 2020, we prospectively included children up to 2 years old presenting with an acute LRTI, both ambulatory and hospitalized.

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Clinicians are increasingly confronted with the limitations of antibiotics to clear bacterial infections in patients. It has long been assumed that only antibiotic resistance plays a pivotal role in this phenomenon. Indeed, the worldwide emergence of antibiotic resistance is considered one of the major health threats of the 21st century.

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Article Synopsis
  • * Peptide nucleic acids offer a novel method for targeting pathogens through antisense strategies, providing a fresh approach to developing effective antibacterial agents.
  • * Due to the resilience of biofilms against conventional antibiotics, alternative treatment methods and efficient drug delivery systems, including in vivo models and nanosystems, are crucial for combating various types of bacterial infections.
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Fosmidomycin is a natural antibiotic with potent IspC (DXR, 1-deoxy-d-xylulose-5-phosphate reductoisomerase) inhibitory activity. This enzyme catalyzes the first committed step of the non-mevalonate isoprenoid biosynthesis pathway, which is essential in most bacteria, including A. baumanii and M.

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Streptococcus pneumoniae is an important human pathogen, being one of the most common causes of community-acquired pneumonia and otitis media. Antibiotic resistance in S. pneumoniae is an emerging problem, as it depletes our arsenal of effective drugs.

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Oxidative stress is an important component of many diseases including cancer, along with inflammatory and neurodegenerative processes. Natural antioxidants have emerged as promising substances to protect the human body against reactive oxygen and nitrogen species. The present study evaluates the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.

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In the search for new anti-mycobacterial agents, we revealed the importance of imidazo-[2,1-]-thiazole and benzo-[]-imidazo-[2,1-]-thiazole carboxamide derivatives. We designed, ADMET predicted and synthesized four series of novel imidazo-[2,1-]-thiazole and benzo-[]-imidazo-[2,1-]-thiazole carboxamide analogues in combination with piperazine and various 1,2,3 triazoles. All the synthesized derivatives were characterized by H NMR, C NMR, HPLC and MS spectral analysis and evaluated for antitubercular activity.

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The increase in antibiotic resistance demands innovative strategies to combat microorganisms. The current study evaluated the antibacterial and antivirulence effects of ethanol extracts from Persea americana seeds obtained by the Soxhlet (SE) and maceration (MaE) methods. The UHPLC-DAD-QTOF analysis showed mainly the presence of polyphenols and neolignan.

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