Novel metabolite madeirone and neomarinone extracted from Streptomyces aculeoletus as marine antibiofilm and antifouling agents.

Introduction: Biofouling poses a significant economic threat to various marine industries, leading to financial losses that can reach billions of euros annually. This study highlights the urgent need for effective alternatives to traditional antifouling agents, particularly following the global ban on organotin compounds. Material and methods: Streptomyces aculeolatus PTM-346 was isolated from sediment samples on the shores of the Madeira Archipelago, Portugal. The crude extract was fractionated using silica flash chromatography and preparative HPLC, resulting in two isolated marinone compounds: madeirone (1), a novel marinone derivative discovered in this study, and neomarinone (2). The antifouling activities of these compounds were tested against five marine bacterial species and the larvae of the mussel Mytilus galloprovincialis. Additionally, in silico and in vivo environmental toxicity evaluations of madeirone (1) and neomarinone (2) were conducted. Results: Madeirone (1) demonstrated significant antibiofilm efficacy, inhibiting Phaeobacter inhibens by up to 66%, Marinobacter hydrocarbonoclasticus by up to 60%, and Cobetia marina by up to 40%. Neomarinone (2) also exhibited substantial antibiofilm activity, with inhibition rates of up to 41% against P. inhibens, 40% against Pseudo-oceanicola batsensis, 56% against M. hydrocarbonoclasticus, 46% against C. marina, and 40% against Micrococcus luteus. The growth inhibition activity at the same concentrations of these compounds remained below 20% for the respective bacteria, highlighting their effectiveness as potent antibiofilm agents without significantly affecting bacterial viability. Additionally, both compounds showed potent effects against the settlement of Mytilus galloprovincialis larvae, with EC50 values of 1.76 µg/mL and 0.12 µg/mL for compounds (1) and (2), respectively, without impairing the viability of the targeted macrofouling species. In silico toxicity predictions and in vivo toxicity assays both support their potential for further development as antifouling agents. Conclusion: The newly discovered metabolite madeirone (1) and neomarinone (2) effectively inhibit both micro- and macrofouling. This distinct capability sets them apart from existing commercial antifouling agents and positions them as promising candidates for biofouling prevention. Consequently, these compounds represent a viable and environmentally friendly alternative for incorporation into paints, primers, varnishes, and sealants, offering significant advantages over traditional copper-based compounds.

Hyponatremia in Cancer Patients Hospitalized in a Palliative Care Department: A Cross-Sectional Analysis.

INTRODUCTION: Hyponatremia is frequent in cancer patients, as many studies carried out in these patients have shown. However, there are only a few studies carried out at the end of life and in palliative care. The aim of this study was to determine the prevalence of hyponatremia in cancer patients in the palliative care department of an oncology center and its association with survival. MATERIAL AND METHODS: The study included the first 300 patients hospitalized in the palliative care department in 2017. Survival was measured from the day of hospitalization until death. RESULTS: Serum sodium was measured in 170 (59%) patients. The median serum concentration was 135 mmol/L (109 to 145). Among 91 (54%) patients, serum sodium was within the normal range, 59 (35%) had mild hyponatremia, 13 (8%) had moderate and seven (4%) had profound hyponatremia. The median survival was 13 days (1 to 1020). Serum sodium was not significantly associated with survival (p = 0.463). Regarding other variables, the Eastern Cooperative Oncology Group performance status was significantly associated with survival, while gender, age, primary cancer and number of metastatic sites were not. DISCUSSION: Hyponatremia, mainly mild and moderate, was found in almost half of the patients included in this study. However, unlike other studies, hyponatremia was not associated with a poorer prognosis. CONCLUSION: Hyponatremia is common in cancer patients receiving palliative care but did not seem to influence survival.

Introdução: A hiponatremia é frequente em doentes com cancro, como muito estudos realizados nesses doentes mostraram. Contudo, há poucos estudos no fim da vida e em cuidados paliativos. O objectivo deste trabalho foi estudar a prevalência da hiponatremia em doentes oncológicos num serviço de cuidados paliativos de um centro oncológico e a sua associação com a sobrevivência. Material e Métodos: O estudo incluiu os primeiros 300 doentes internados no serviço de cuidados paliativos em 2017. A sobrevivência foi medida do dia da hospitalização até à morte. Resultados: O sódio plasmático foi medido em 170 (59%) doentes. A mediana da concentração de sódio plasmático foi 135 mmol/L (109 a 145). Em 91 (54%) doentes, o sódio plasmático estava dentro dos valores de referência, 59 (35%) tinham hiponatremia ligeira, em 13 (8%) era moderada e sete (4%) tinham hiponatremia profunda. A mediana da sobrevivência foi de 13 dias (1 a 1020). O sódio plasmático não apresentou uma associação estatisticamente significativamente associado com a sobrevivência (p = 0,463). Quanto a outras variáveis, o estado de performance do Eastern Cooperative Oncology Group associou-se significativamente à sobrevivência, o que não se verificou com o género, a idade, o tumor primário e o número de locais de metástases. Discussão: A hiponatremia, principalmente ligeira e moderada, ocorreu em quase metade dos doentes incluídos neste estudo. No entanto, ao contrário de outros estudos, a hiponatremia não se associou a um pior prognóstico. Conclusão: A hiponatremia é comum nos doentes oncológicos em cuidados paliativos, mas não parece influenciar a sobrevivência.

The Diversity, Metabolomics Profiling, and the Pharmacological Potential of Actinomycetes Isolated from the Estremadura Spur Pockmarks (Portugal).

The Estremadura Spur pockmarks are a unique and unexplored ecosystem located in the North Atlantic, off the coast of Portugal. A total of 85 marine-derived actinomycetes were isolated and cultured from sediments collected from this ecosystem at a depth of 200 to 350 m. Nine genera, Streptomyces, Micromonospora, Saccharopolyspora, Actinomadura, Actinopolymorpha, Nocardiopsis, Saccharomonospora, Stackebrandtia, and Verrucosispora were identified by 16S rRNA gene sequencing analyses, from which the first two were the most predominant. Non-targeted LC-MS/MS, in combination with molecular networking, revealed high metabolite diversity, including several known metabolites, such as surugamide, antimycin, etamycin, physostigmine, desferrioxamine, ikarugamycin, piericidine, and rakicidin derivatives, as well as numerous unidentified metabolites. Taxonomy was the strongest parameter influencing the metabolite production, highlighting the different biosynthetic potentials of phylogenetically related actinomycetes; the majority of the chemical classes can be used as chemotaxonomic markers, as the metabolite distribution was mostly genera-specific. The EtOAc extracts of the actinomycete isolates demonstrated antimicrobial and antioxidant activity. Altogether, this study demonstrates that the Estremadura Spur is a source of actinomycetes with potential applications for biotechnology. It highlights the importance of investigating actinomycetes from unique ecosystems, such as pockmarks, as the metabolite production reflects their adaptation to this habitat.

Antifouling Napyradiomycins from Marine-Derived Actinomycetes Streptomyces aculeolatus.

The undesired attachment of micro and macroorganisms on water-immersed surfaces, known as marine biofouling, results in severe prevention and maintenance costs (billions €/year) for aquaculture, shipping and other industries that rely on coastal and off-shore infrastructures. To date, there are no sustainable, cost-effective and environmentally safe solutions to address this challenging phenomenon. Therefore, we investigated the antifouling activity of napyradiomycin derivatives that were isolated from actinomycetes from ocean sediments collected off the Madeira Archipelago. Our results revealed that napyradiomycins inhibited ≥80% of the marine biofilm-forming bacteria assayed, as well as the settlement of Mytilus galloprovincialis larvae (EC50 < 5 µg/ml and LC50/EC50 >15), without viability impairment. In silico prediction of toxicity end points are of the same order of magnitude of standard approved drugs and biocides. Altogether, napyradiomycins disclosed bioactivity against marine micro and macrofouling organisms, and non-toxic effects towards the studied species, displaying potential to be used in the development of antifouling products.

Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan.

Glutamate amidation, a secondary modification of the peptidoglycan, was first identified in Staphylococcus aureus It is catalyzed by the protein products of the murT and gatD genes, which are conserved and colocalized in the genomes of most sequenced Gram-positive bacterial species. The MurT-GatD complex is required for cell viability, full resistance to ß-lactam antibiotics, and resistance to human lysozyme and is recognized as an attractive target for new antimicrobials. Great effort has been invested in the study of this step, culminating recently in three independent reports addressing the structural elucidation of the MurT-GatD complex. In this work, we demonstrate through the use of nonstructural approaches the critical and multiple roles of the C-terminal domain of MurT, annotated as DUF1727, in the MurT-GatD enzymatic complex. This domain provides the physical link between the two enzymatic activities and is essential for the amidation reaction. Copurification of recombinant MurT and GatD proteins and bacterial two-hybrid assays support the observation that the MurT-GatD interaction occurs through this domain. Most importantly, we provide in vivo evidence of the effect of substitutions at specific residues in DUF1727 on cell wall peptidoglycan amidation and on the phenotypes of oxacillin resistance and bacterial growth.

Genomic identification of cryptic susceptibility to penicillins and ß-lactamase inhibitors in methicillin-resistant Staphylococcus aureus.

Antibiotic resistance in bacterial pathogens threatens the future of modern medicine. One such resistant pathogen is methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to nearly all ß-lactam antibiotics, limiting treatment options. Here, we show that a significant proportion of MRSA isolates from different lineages, including the epidemic USA300 lineage, are susceptible to penicillins when used in combination with ß-lactamase inhibitors such as clavulanic acid. Susceptibility is mediated by a combination of two different mutations in the mecA promoter region that lowers mecA-encoded penicillin-binding protein 2a (PBP2a) expression, and in the majority of isolates by either one of two substitutions in PBP2a (E246G or M122I) that increase the affinity of PBP2a for penicillin in the presence of clavulanic acid. Treatment of S. aureus infections in wax moth and mouse models shows that penicillin/ß-lactamase inhibitor susceptibility can be exploited as an effective therapeutic choice for 'susceptible' MRSA infection. Finally, we show that isolates with the PBP2a E246G substitution have a growth advantage in the presence of penicillin but the absence of clavulanic acid, which suggests that penicillin/ß-lactamase susceptibility is an example of collateral sensitivity (resistance to one antibiotic increases sensitivity to another). Our findings suggest that widely available and currently disregarded antibiotics could be effective in a significant proportion of MRSA infections.

Intra-clade metabolomic profiling of MAR4 Streptomyces from the Macaronesia Atlantic region reveals a source of anti-biofilm metabolites.

The search for new and effective strategies to reduce bacterial biofilm formation is of utmost importance as bacterial resistance to antibiotics continues to emerge. The use of anti-biofilm agents that can disrupt recalcitrant bacterial communities can be an advantageous alternative to antimicrobials, as their use does not lead to the development of resistance mechanisms. Six MAR4 Streptomyces strains isolated from the Madeira Archipelago, at the unexplored Macaronesia Atlantic ecoregion, were used to study the chemical diversity of produced hybrid isoprenoids. These marine actinomycetes were investigated by analysing their crude extracts using LC-MS/MS and their metabolomic profiles were compared using multivariate statistical analysis (principal component analysis), showing a separation trend closely related to their phylogeny. Molecular networking unveiled the presence of a class of metabolites not previously described from MAR4 strains and new chemical derivatives belonging to the napyradiomycin and marinone classes. Furthermore, these MAR4 strains produce metabolites that inhibit biofilm formation of Staphylococcus aureus and Marinobacter hydrocarbonoclasticus. The anti-biofilm activity of napyradiomycin SF2415B3 (1) against S. aureus was confirmed.

Role of intravenous iron in the treatment of anemia in patients with gastrointestinal tract tumors undergoing chemotherapy: a single-center, observational study.

PURPOSE: The prevalence of anemia ranges between 30% and 90% in cancer patients, affecting the health status, quality of life, and treatment outcome. Therefore, a proper diagnosis and management of anemia is crucial in these patients. Iron deficiency is diagnosed in~32%-60% of the cases. In this observational study, we evaluated the efficacy and safety of intravenous iron (ferric carboxymaltose [FCM], Ferinject®) in the treatment of iron-deficiency anemia in patients with gastrointestinal tumors undergoing palliative or adjuvant chemotherapy. PATIENTS AND METHODS: Thirty patients with gastrointestinal tumors undergoing chemotherapy diagnosed with iron-deficiency anemia were included in the study and received at least one FCM administration. The need for iron replacement therapy was evaluated by the assessment of hemoglobin and iron status parameters, and patients could be treated with FCM during 12-14 weeks. Paired t-test approach was used to evaluate the mean differences between the baseline and the end of the study. A p-value of <0.05 was considered statistically significant. RESULTS: Data showed that there was a statistically significant increase in the mean of hemoglobin (10.3 vs 11.2 g/dL), ferritin (230.3 vs 877.0 ng/mL), transferrin saturation (13.0% vs 19.7%), and serum iron (42.3 vs 59.6 mg/mL) from the baseline to the end of the study in cancer patients. Most of the patients (n=25) were only administered one dose of FCM. There was one FCM-related adverse event during the study. CONCLUSION: FCM was well tolerated and had a positive impact in the treatment of iron-deficiency anemia in patients with gastrointestinal tract tumors undergoing chemotherapy.

Qualidade de vida familiar, satisfação com a vida e apoio social percebido na deficiência visual / Family quality of life, satisfaction with life and perceived social support in visual impairment / Calidad de la vida familiar, satisfacción con la vida y el apoyo social percibido en la discapacidad visual

O estudo da influência da deficiência visual no indivíduo permanece ainda com questões por responder. Esta pesquisa comparou a qualidade de vida familiar, satisfação com a vida e apoio social percebido numa amostra de sujeitos adultos com deficiência visual (n = 52) e normovisuais (n = 52). Verificaram-se diferenças estatisticamente significativas, com o grupo com deficiência visual a apresentar resultados superiores nos fatores Tempo e Emprego do QOL e resultados inferiores no fator Mass Media do QOL e na subescala Vinculação da EPS. Obtiveram-se diferenças estatisticamente significativas entre as variáveis demográficas e a qualidade de vida familiar e o apoio social percebido, nas variáveis sexo (resultado superior no sexo masculino), idade (resultados mais elevados entre 18-35 anos) e situação profissional (resultados superiores em sujeitos empregados), no grupo com deficiência visual. Apesar do contributo deste trabalho, são necessários mais estudos para clarificar a influência da deficiência visual no indivíduo, como também na família.(AU).

The study of the influence of visual impairment on the individual still remains with unanswered questions. This research compared the quality of family life, life satisfaction and perceived social support in a sample of adult with visual impairment (n = 52) and sighted (n = 52) using. There were obtained statistically significant differences with the group with visual impairment providing superior results in the factors Time and Employment of the QOL, lower results in the factor Mass Media of the QOL and the subscale Attachment of the EPS. There was obtained statistically significant differences between demographic variables and the quality of family life and perceived social support, on the variables gender (higher result in males), age (higher results from 18-35 years), and employment status (superior results in employed subjects), in the group with visual disabilities. Despite the contribution of this study, further studies are needed to clarify the influence of visual impairment on the individual but also the family.(AU).

El estudio de la influencia de la discapacidad visual en el individuo permanece aún con preguntas sin respuesta. Este estudio comparó la calidad de la vida familiar, satisfacción con la vida y el apoyo social percibido en una muestra de sujetos adultos con discapacidad visual (n = 52) y normovisuais (n = 52). Se comprobaron diferencias estadísticamente significativas, con el grupo con deficiencia visual mostrando resultados superiores en los factores Tiempo y Empleo del QOL, y menores resultados en los Mass Media del QOL y la subescala de Vinculación de la EPS. Se han encontrado diferencias estadísticamente significativas entre las variables demográficas y la calidad de la vida familiar y el apoyo social percibido, en las variables sexo (mayor resultado en los hombres), edad (resultados mayores de 18-35 años) y situación laboral (resultados superiores en los sujetos empleados), en el grupo con discapacidades visuales. A pesar de la contribución de este estudio, son necesarios más estudios para aclarar la influencia de la discapacidad visual en el individuo, sino también en la familia.(AU).

Bacterial autolysins trim cell surface peptidoglycan to prevent detection by the Drosophila innate immune system.

Bacteria have to avoid recognition by the host immune system in order to establish a successful infection. Peptidoglycan, the principal constituent of virtually all bacterial surfaces, is a specific molecular signature recognized by dedicated host receptors, present in animals and plants, which trigger an immune response. Here we report that autolysins from Gram-positive pathogenic bacteria, enzymes capable of hydrolyzing peptidoglycan, have a major role in concealing this inflammatory molecule from Drosophila peptidoglycan recognition proteins (PGRPs). We show that autolysins trim the outermost peptidoglycan fragments and that in their absence bacterial virulence is impaired, as PGRPs can directly recognize leftover peptidoglycan extending beyond the external layers of bacterial proteins and polysaccharides. The activity of autolysins is not restricted to the producer cells but can also alter the surface of neighboring bacteria, facilitating the survival of the entire population in the infected host. DOI: http://dx.doi.org/10.7554/eLife.02277.001.

The glucosaminidase domain of Atl - the major Staphylococcus aureus autolysin - has DNA-binding activity.

In this communication, we describe evidence demonstrating the capacity of Atl, the major Staphylococcus aureus autolytic enzyme to bind DNA. Electrophoretic mobility shift assays (EMSA) show that both the Atl protein and the endo-ß-N-acetylglucosaminidase (GL) domain were able to bind DNA of nonspecific sequence. The implications of this unexpected observation for the physiology of S. aureus remain to be explored.