Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.

Structural Characterization and Bioactivity of a Titanium(IV)-Oxo Complex Stabilized by Mandelate Ligands.

Research on titanium-oxo complexes (TOCs) is usually focused on their structure and photocatalytic properties. Findings from these investigations further sparked our interest in exploring their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the evaluation of the antimicrobial activity of the obtained materials. The investigations performed demonstrated the antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, which is also may be use for producing composite coatings.

Streptantibioticus silvisoli sp. nov., acidotolerant actinomycetes from pine litter, reclassification of Streptomyces cocklensis, Streptomyces ferralitis, Streptomyces parmotrematis and Streptomyces rubrisoli as Actinacidiphila cocklensis comb. nov., Streptantibioticus ferralitis comb. nov., Streptantibioticus parmotrematis comb. nov. and Streptantibioticus rubrisoli comb. nov., and emended descriptions of the genus Streptantibioticus, the family Streptomycetaceae and Streptomyces iconiensis.

Filamentous actinomycetes, designated SL13 and SL54T, were isolated from pine litter and their taxonomic status resolved using a polyphasic approach. The isolates exhibit chemotaxonomic and morphological properties consistent with their classification in the family Streptomycetaceae. They form extensively branched substrate mycelia bearing aerial hyphae that differentiate into straight chains of cylindrical spores. The whole-organism hydrolysates contain ll-diaminopimelic acid, glucose, mannose and ribose, the predominant isoprenologue is MK-9(H8), the polar lipids are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and glycophospholipids, and the major fatty acids are anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. Phylogenetic trees based on 16S rRNA gene sequences and multilocus gene sequences of conserved housekeeping genes show that the isolates form a well-supported lineage that is most closely related to Streptomyces parmotrematis NBRC 115203T. All of these strains form a well-defined clade in the multilocus sequence analysis tree together with Streptantibioticus cattleyicolor DSM 46488T, Streptomyces ferralitis DSM 41836T and Streptomyces rubrisoli DSM 42083T. Draft genomes assemblies of the isolates are rich in biosynthetic gene clusters predicted to produce novel specialized metabolites and stress-related genes which provide an insight into how they have adapted to the harsh conditions that prevail in pine litter. Phylogenomically, both isolates belong to the same lineage as the type strains of S. cattleyicolor, S. ferralitis, S. parmotrematis and S. rubrisoli; these relationships are underpinned by high average amino acid identity, average nucleotide identity and genomic DNA-DNA hybridization values. These metrics confirm that isolates SL13 and SL54T belong to a novel species that is most closely related to S. parmotrematis NBRC 115203T and that these strains together with S. ferralitis DSM 41836T, S. rubrisoli DSM 42083T belong to the genus Streptantibioticus. Consequently, it is proposed that the isolates be recognized as a new Streptantibioticus species, Streptantibioticus silvisoli comb. nov., with isolate SL54T (=DSM 111111T=PCM3044T) as the type strain, and that S. ferralitis, S. parmotrematis and S. rubrisoli be transferred to the genus Streptantibioticus as Streptantibioticus ferralitis comb. nov., Streptantibioticus parmotrematis comb. nov. and Streptantibioticus rubrisoli comb. nov. Emended descriptions are given for the genus Streptantibioticus, the family Streptomycetaceae and for Streptomyces iconiensis which was found to be a close relative of the isolates in the 16S rRNA gene sequence analyses. It is also proposed that Streptomyces cocklensis be transferred to the genus Actinacidiphila as Actinacidiphila cocklensis comb. nov based on its position in the MLSA and phylogenomic trees and associated genomic data.

Comparative Host-Pathogen Interaction Analyses of SARS-CoV2 and Aspergillus fumigatus, and Pathogenesis of COVID-19-Associated Aspergillosis.

COVID-19 caused a global catastrophe with a large number of cases making it one of the major pandemics of the human history. The clinical presentations of the disease are continuously challenging healthcare workers with the variation of pandemic waves and viral variants. Recently, SARS-CoV2 patients have shown increased occurrence of invasive pulmonary aspergillosis infection even in the absence of traditional risk factors. The mechanism of COVID-19-associated aspergillosis is not completely understood and therefore, we performed this system biological study in order to identify mechanistic implications of aspergillosis susceptibility in COVID-19 patients and the important targets associated with this disease. We performed host-pathogen interaction (HPI) analysis of SARS-CoV2, and most common COVID-19-associated aspergillosis pathogen, Aspergillus fumigatus, using in silico approaches. The known host-pathogen interactions data of SARS-CoV2 was obtained from BIOGRID database. In addition, A. fumigatus host-pathogen interactions were predicted through homology modeling. The human targets interacting with both pathogens were separately analyzed for their involvement in aspergillosis. The aspergillosis human targets were screened from DisGeNet and GeneCards. The aspergillosis targets involved in both HPI were further analyzed for functional overrepresentation analysis using PANTHER. The results indicate that both pathogens interact with a number of aspergillosis targets and altogether they recruit more aspergillosis targets in host-pathogen interaction than alone. Common aspergillosis targets involved in HPI with both SARS-CoV2 and A. fumigatus can indicate strategies for the management of both conditions by modulating these common disease targets.

Engineered nanomaterials in plant diseases: can we combat phytopathogens?

Engineered nanomaterials (ENM) have a high potential for use in several areas of agriculture including plant pathology. Nanoparticles (NPs) alone can be applied for disease management due to their antimicrobial properties. Moreover, nanobiosensors allow a rapid and sensitive diagnosis of pathogens because NPs can be conjugated with nucleic acids, proteins and other biomolecules. The use of ENM in diagnosis, delivery of fungicides and therapy is an eco-friendly and economically viable alternative. This review focuses on different promising studies concerning ENM used for plant disease management including viruses, fungi, oomycetes and bacteria; diagnosis and delivery of antimicrobials and factors affecting the efficacy of nanomaterials, entry, translocation and toxicity. Although much research is required on metallic NPs due to the possible risks to the final consumer, ENMs are undoubtedly very useful tools to achieve food security in the world. KEY POINTS: • Increasing global population and fungicides have necessitated alternative technologies. • Nanomaterials can be used for detection, delivery and therapy of plant diseases. • The toxicity issues and safety should be considered before the use of nanomaterials.

Genome-based classification of Streptomyces pinistramenti sp. nov., a novel actinomycete isolated from a pine forest soil in Poland with a focus on its biotechnological and ecological properties.

A genomic-based polyphasic study was undertaken to establish the taxonomic status and biotechnological and ecological potential of a Streptomyces strain, isolate SF28T, that was recovered from the litter layer in a Polish Pinus sylvestris forest. The isolate had morphological characteristics and chemotaxonomic properties consistent with its classification in the genus Streptomyces. It formed long straight chains of spores with smooth surfaces, contained LL-diaminopimelic acid, glucose and ribose in whole-organism hydrolysates, produced major proportions of straight, iso- and anteiso- fatty acids, hexa- and octa-hydrogenated menaquinones with nine isoprene units and had a polar lipid pattern composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, glycophospholipids and three uncharacterized components. Phylogenetic trees prepared using 16S rRNA gene and multilocus gene sequences of conserved housekeeping genes showed that the isolate formed a branch that was loosely associated with the type strains of several validly published Streptomyces species. A draft genome generated for the isolate was rich in natural product-biosynthetic gene clusters with the potential to produce new specialised metabolites, notably antibiotics, and stress related genes which provide an insight into how it may have become adapted to the harsh conditions that prevail in acidic forest soils. A phylogenomic tree based on the genomes of the isolate and its phylogenetic neighbours confirmed that it formed a distinct lineage well separated from its closest evolutionary relatives. The isolate shared low average nucleotide identity and digital DNA:DNA hybridization values with its phylogenomic neighbours and was also distinguished from them using a combination of cultural and micromorphological properties. Given this wealth of taxonomic data it is proposed that isolate SF28T (= DSM 113360 T = PCM 3163 T) be classified in the genus Streptomyces as Streptomyces pinistramenti sp. nov. The isolate showed pronounced antimicrobial activity, especially against fungal plant pathogens.

Antibacterial Properties of Crotoxin from Crotalus durissus terrificus-Insight into the Mechanism of Action.

The growing problem of antibiotic resistance among bacteria requires searching for new therapeutic agents with bacteriostatic and/or bactericidal properties. Crotoxin is a ß-neurotoxin from the venom of the Crotalus durissus terrificus. It is composed of two subunits: CA (non-active) and CB (with phospholipase A2 activity). It has already been shown that the isolated CB, but not the CA, subunit of crotoxin exhibits an antibacterial activity towards a variety of Gram-positive and Gram-negative bacterial species. However, no studies on the whole crotoxin complex have been carried out so far. We tested the antibacterial properties of crotoxin, as well as its isolated CB subunit, towards Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 6535, Micrococcus luteus ATCC 10240, Escherichia coli ATCC 25922, Escherichia coli ATCC 8739, and Pseudomonas aeruginosa ATCC 10145. Both toxins exhibited antibacterial properties only against Micrococcus luteus ATCC 10240. Crotoxin showed only bacteriostatic activity with a MIC of 46 µM, while the CB subunit acted as both a bacteriostatic and bactericidal agent with a MIC = MBC = 0.21 µM. The bacteriostatic effect of the toxins was independent of the enzymatic activity of the CB subunit. Bactericidal properties, however, require phospholipase A2 activity. Both toxins reduced bacteria viability at the MIC by 72% and 85% for crotoxin- and CB-treated bacteria, respectively. The membrane permeability increased approximately three times within the first hour of incubation with toxins; afterwards, either no significant changes or a decrease of membrane permeability, compared to the control cells, were observed. We isolated a single, approximately 30 kDa bacterial wall protein which belongs to the NlpC/P60 family that interacts with crotoxin leading to the inhibition of bacterial growth. Neither crotoxin nor the CB subunit showed any cytotoxic properties to human fibroblasts at the MIC during the three-day incubation.

Catenulispora pinistramenti sp. nov., novel actinobacteria isolated from pine forest soil in Poland.

The taxonomic status of two filamentous actinobacteria, isolates NF23 and NL8T, recovered from the litter layer of a pine forest soil in Poland was established in a genome-based polyphasic study. The isolates showed a combination of chemotaxonomic, morphological and physiological properties associated with their classification in the genus Catenulispora. They formed a well supported lineage within the Catenulispora 16S rRNA gene tree and were most closely related to the type strains of Catenulispora acidiphila (99.1%), Catenulispora pinisilvae (99.9 %) and Catenulispora rubra (99.1 %), and like them, were found to have large genomes (10.8 and 11.5 Mbp, respectively). A phylogenomic tree based on the draft genomes of isolates NF23 and NL8T and their phylogenetic neighbours showed that they formed a distinct branch in the Catenulispora clade that was most closely related to C. pinisilvae DSM 111109T. The isolates shared a combination of genomic, genotypic and phenotypic features, and had high average nucleotide index (ANI) and digital DNA:DNA hybridization (dDDH) similarities consistent with their assignment to the same species. The isolates were distinguished from the C. acidiphila, C. pinisilvae and C. rubra strains by a wealth of taxonomic data and by low ANI (84.9-93.9 %) and dDDH (29.6-54.7 %) values. It is proposed that the isolates be classified in the genus Catenulispora as C. pinistramenti sp. nov. with isolate NL8T (=DSM 111110T=PCM 3045T) as the type strain. The genomes of strains NF23 and NL8T are rich in natural product-biosynthetic gene clusters hence these strains have the potential to synthesize new specialised metabolites.

Emerging Trends in Pullulan-Based Antimicrobial Systems for Various Applications.

Global reports on multidrug resistance (MDR) and life-threatening pathogens such as SARS-CoV-2 and Candida cruris have stimulated researchers to explore new antimicrobials that are eco-friendly and economically viable. In this context, biodegradable polymers such as nisin, chitin, and pullulan play an important role in solving the problem. Pullulan is an important edible, biocompatible, water-soluble polymer secreted by Aureobasidium pullulans that occurs ubiquitously. It consists of maltotriose units linked with α-1,6 glycosidic bonds and is classed as Generally Regarded as Safe (GRAS) by the Food and Drug Administration (FDA) in the USA. Pullulan is known for its antibacterial, antifungal, antiviral, and antitumor activities when incorporated with other additives such as antibiotics, drugs, nanoparticles, and so on. Considering the importance of its antimicrobial activities, this polymer can be used as a potential antimicrobial agent against various pathogenic microorganisms including the multidrug-resistant (MDR) pathogens. Moreover, pullulan has ability to synthesize biogenic silver nanoparticles (AgNPs), which are remarkably efficacious against pathogenic microbes. The pullulan-based nanocomposites can be applied for wound healing, food packaging, and also enhancing the shelf-life of fruits and vegetables. In this review, we have discussed biosynthesis of pullulan and its role as antibacterial, antiviral, and antifungal agent. Pullulan-based films impregnated with different antimicrobials such as AgNPs, chitosan, essential oils, and so on, forming nanocomposites have also been discussed as natural alternatives to combat the problems posed by pathogens.

The Composites of PCL and Tetranuclear Titanium(IV)-oxo Complexes as Materials Exhibiting the Photocatalytic and the Antimicrobial Activity.

Excessive misuse of antibiotics and antimicrobials has led to a spread of microorganisms resistant to most currently used agents. The resulting global threats has driven the search for new materials with optimal antimicrobial activity and their application in various areas of our lives. In our research, we focused on the formation of composite materials produced by the dispersion of titanium(IV)-oxo complexes (TOCs) in poly(ε-caprolactone) (PCL) matrix, which exhibit optimal antimicrobial activity. TOCs, of the general formula [Ti4O2(OiBu)10(O2CR')2] (R' = PhNH2 (1), C13H9 (2)) were synthesized as a result of the direct reaction of titanium(IV) isobutoxide and 4-aminobenzoic acid or 9-fluorenecarboxylic acid. The microcrystalline powders of (1) and (2), whose structures were confirmed by infrared (IR) and Raman spectroscopy, were dispersed in PCL matrixes. In this way, the composites PCL + nTOCs (n = 5 and 20 wt.%) were produced. The structure and physicochemical properties were determined on the basis of Raman microscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), electron paramagnetic resonance spectroscopy (EPR), and UV-Vis diffuse reflectance spectroscopy (DRS). The degree of TOCs distribution in the polymer matrix was monitored by scanning electron microscopy (SEM). The addition of TOCs micro grains into the PCL matrix only slightly changed the thermal and mechanical properties of the composite compared to the pure PCL. Among the investigated PCL + TOCs systems, promising antibacterial properties were confirmed for samples of PCL + n(2) (n = 5, 20 wt.%) composites, which simultaneously revealed the best photocatalytic activity in the visible range.

Modestobacter altitudinis sp. nov., a novel actinobacterium isolated from Atacama Desert soil.

Three presumptive Modestobacter strains isolated from a high altitude Atacama Desert soil were the subject of a polyphasic study. The isolates, strains 1G4T, 1G51 and 1G52, were found to have chemotaxonomic and morphological properties that were consistent with their assignment to the genus Modestobacter. They formed a well supported clade in Modestobacter 16S rRNA gene trees and were most closely related to the type strain of 'Modestobacter excelsi' (99.8-99.9% similarity). They were also closely related to the type strains of Modestobacter caceresii (99.6 % similarity), Modestobacter italicus (99.7-99.9% similarity), Modestobacter lacusdianchii (98.4-99.2% similarity), Modestobacter marinus (99.4-99.5% similarity) and Modestobacter roseus (99.3-99.5% similarity), but were distinguished from their closest relatives by a combination of phenotypic features. Average nucleotide identity and digital DNA:DNA hybridization similarities drawn from comparisons of draft genome sequences of isolate 1G4T and its closest phylogenetic neighbours mentioned above, were well below the threshold used to assign closely related strains to the same species. The close relationship between isolate 1G4T and the type strain of M. excelsi was showed in a phylogenomic tree containing representative strains of family Geodermatophilaceae. The draft genome sequence of isolate 1G4T (size 5.18 Kb) was shown to be rich in stress related genes providing further evidence that the abundance of Modestobacter propagules in Atacama Desert habitats reflects their adaptation to the harsh environmental conditions prevalent in this biome. In light of all of these data it is proposed that the isolates be assigned to a novel species in the genus Modestobacter. The name proposed for this taxon is Modestobacter altitudinis sp. nov., with isolate 1G4T (=DSM 107534T=PCM 3003T) as the type strain.

Oxo-Titanium(IV) Complex/Polymer Composites-Synthesis, Spectroscopic Characterization and Antimicrobial Activity Test.

The emergence of a large number of bacterial strains resistant to many drugs or disinfectants currently used contributed to the search of new, more effective antimicrobial agents. In the presented paper, we assessed the microbiocidal activity of tri- and tetranuclear oxo-titanium(IV) complexes (TOCs), which were dispersed in the poly(methyl methacrylate) (PMMA) matrix. The TOCs were synthesized in reaction to Ti(OR)4 (R = iPr, iBu) and HO2CR' (R' = 4-PhNH2 and 4-PhOH) in a 4:1 molar ratio at room temperature and in Ar atmosphere. The structure of isolated oxo-complexes was confirmed by IR and Raman spectroscopy and mass spectrometry. The antimicrobial activity of the produced composites (PMMA + TOCs) was estimated against Gram-positive (Staphylococcus aureus ATCC 6538 and S. aureus ATCC 25923) and Gram-negative (Escherichia coli ATCC 8739 and E. coli ATCC 25922) bacteria and yeasts of Candida albicans ATCC 10231. All produced composites showed biocidal activity against the bacteria. Composites containing {Ti4O2} cores and the {Ti3O} core stabilized by the 4-hydroxybenzoic ligand showed also high activity against yeasts. The results of investigations carried out suggest that produced (PMMA + TOCs) composites, due to their microbiocidal activity, could find an application in the elimination of microbial contaminations in various fields of our lives.

Biogenic Silver Nanoparticles: Assessment of Their Cytotoxicity, Genotoxicity and Study of Capping Proteins.

The development of nanotechnology in the last two decades has led to the use of silver nanoparticles (AgNPs) in various biomedical applications, including antimicrobial, anti-inflammatory, and anticancer therapies. However, the potential of the medical application of AgNPs depends on the safety of their use. In this work, we assessed the in vitro cytotoxicity and genotoxicity of silver nanoparticles and identified biomolecules covering AgNPs synthesized from actinobacterial strain SH11. The cytotoxicity of AgNPs against MCF-7 human breast cancer cell line and murine macrophage cell line RAW 264.7 was studied by MTT assay, cell LDH (lactate dehydrogenase) release, and the measurement of ROS (reactive oxygen species) level while genotoxicity in Salmonella typhimurium cells was testing using the Ames test. The in vitro analysis showed that the tested nanoparticles demonstrated dose-dependent cytotoxicity against RAW 264.6 macrophages and MCF-7 breast cancer cells. Moreover, biosynthesized AgNPs did not show a mutagenic effect of S. typhimurium. The analyses and identification of biomolecules present on the surface of silver nanoparticles showed that they were associated with proteins. The SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis revealed the presence of 34 and 43 kDa protein bands. The identification of proteins performed by using LC-MS/MS (liquid chromatography with tandem mass spectrometry) demonstrated their highest homology to bacterial porins. Capping biomolecules of natural origin may be involved in the synthesis process of AgNPs or may be responsible for their stabilization. Moreover, the presence of natural proteins on the surface of bionanoparticles eliminates the postproduction steps of capping which is necessary for chemical synthesis to obtain the stable nanostructures required for application in medicine.

Micromonospora acroterricola sp. nov., a novel actinobacterium isolated from a high altitude Atacama Desert soil.

A Micromonospora strain, designated 5R2A7T, isolated from a high altitude Atacama Desert soil was examined by using a polyphasic approach. Strain 5R2A7T was found to have morphological, chemotaxonomic and cultural characteristics typical of members of the genus Micromonospora. The cell wall contains meso- and hydroxy-diaminopimelic acid, the major whole-cell sugars are glucose, ribose and xylose, the predominant menaquinones MK-10(H4), MK-10(H6), MK-10(H8) and MK-9(H6), the major polar lipids diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and an unknown glycolipid, and the predominant cellular fatty acids iso-C16 : 0, iso-C15 : 0 and 10-methyl C17 : 0. The digital genomic DNA G+C content is 72.3 mol%. Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain 5R2A7T was closely related to Micromonospora coriariae DSM 44875T (99.8 %) and Micromonospora cremea CR30T (99.7 %), and was separated readily from the latter, its closest phylogenetic neighbour, based on gyrB and multilocus sequence data, by low average nucleotide identity (92.59 %) and in silico DNA-DNA relatedness (51.7 %) values calculated from draft genome assemblies and by a range of chemotaxonomic and phenotypic properties. Consequently, strain 5R2A7T is considered to represent a novel species of Micromonospora for which the name Micromonospora acroterricola sp. nov. is proposed. The type strain is 5R2A7T (=LMG 30755T=CECT 9656T).

Evaluation of antibacterial efficacy of sulfur nanoparticles alone and in combination with antibiotics against multidrug-resistant uropathogenic bacteria.

Urinary tract infections (UTIs) have been frequently reported from different parts of the world. The current knowledge on distribution of causative agents of urinary infections and antibiotics susceptibility pattern is essentially required. In the present study, total 351 uropathogenic bacteria were isolated; among them most prevalent were Escherichia coli (75%), followed by Pseudomonas aeruginosa (8%), Proteus mirabilis (6%), Klebsiella pneumoniae (4%), Staphylococcus aureus (4%) and Enterococcus faecalis (3%). Most isolates of uropathogenic bacteria showed resistance to amoxicillin and trimethoprim, followed by chloramphenicol and kanamycin. Biosynthesis of sulfur nanoparticles (SNPs) was performed by co-precipitation method using sodium thiosulfate in presence of Catharanthus roseus leaf extract. The characterization data showed that SNPs were polydispersed, spherical in shape with size range of 20-86 nm and having negative zeta potential of -9.24 mV. The potential antibacterial activity was observed for SNPs alone and in combination with antibiotics particularly amoxicillin and trimethoprim against majority of the uropathogens. The synergistic effect yielded increase in fold area with high activity index against tested uropathogens. Based on overall results, it can be recommended to use SNPs for the management of UTI alone and also in combination with antibiotics.

Hunting for cultivable Micromonospora strains in soils of the Atacama Desert.

Innovative procedures were used to selectively isolate small numbers of Micromonospora strains from extreme hyper-arid and high altitude Atacama Desert soils. Micromonosporae were recognised on isolation plates by their ability to produce filamentous microcolonies that were strongly attached to the agar. Most of the isolates formed characteristic orange colonies that lacked aerial hyphae and turned black on spore formation, whereas those from the high altitude soil were dry, blue-green and covered by white aerial hyphae. The isolates were assigned to seven multi- and eleven single-membered groups based on BOX-PCR profiles. Representatives of the groups were assigned to either multi-membered clades that also contained marker strains or formed distinct phyletic lines in the Micromonospora 16S rRNA gene tree; many of the isolates were considered to be putatively novel species of Micromonospora. Most of the isolates from the high altitude soils showed activity against wild type strains of Bacillus subtilis and Pseudomonas fluorescens while those from the rhizosphere of Parastrephia quadrangulares and from the Lomas Bayas hyper-arid soil showed resistance to UV radiation.

Synthesis, characterization and evaluation of antimicrobial and cytotoxic activities of biogenic silver nanoparticles synthesized from Streptomyces xinghaiensis OF1 strain.

We report synthesis of silver nanoparticles (AgNPs) from Streptomyces xinghaiensis OF1 strain, which were characterised by UV-Vis and Fourier transform infrared spectroscopy, Zeta sizer, Nano tracking analyser, and Transmission electron microscopy. The antimicrobial activity of AgNPs alone, and in combination with antibiotics was evaluated against bacteria, namely Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis, and yeasts viz., Candida albicans and Malassezia furfur by using micro-dilution method. The minimum inhibitory concentration (MIC) and minimum biocidal concentration of AgNPs against bacterial and yeast strains were determined. Synergistic effect of AgNPs in combination with antibacterial and antifungal antibiotics was determined by FIC index. In addition, MTT assay was performed to study cytotoxicity of AgNPs alone and in combination with antibiotics against mouse fibroblasts and HeLa cell line. Biogenic AgNPs were stable, spherical, small, polydispersed and capped with organic compounds. The variable antimicrobial activity of AgNPs was observed against tested bacteria and yeasts. The lowest MIC (16 µg ml-1) of AgNPs was found against P. aeruginosa, followed by C. albicans and M. furfur (both 32 µg ml-1), B. subtilis and E. coli (both 64 µg ml-1), and then S. aureus and Klebsiella pneumoniae (256 µg ml-1). The high synergistic effect of antibiotics in combination with AgNPs against tested strains was found. The in vitro cytotoxicity of AgNPs against mouse fibroblasts and cancer HeLa cell lines revealed a dose dependent potential. The IC50 value of AgNPs was found in concentrations of 4 and 3.8 µg ml-1, respectively. Combination of AgNPs and antibiotics significantly decreased concentrations of both antimicrobials used and retained their high antibacterial and antifungal activity. The synthesis of AgNPs using S. xinghaiensis OF1 strain is an eco-friendly, cheap and nontoxic method. The antimicrobial activity of AgNPs could result from their small size. Remarkable synergistic effect of antibiotics and AgNPs offer their valuable potential in nanomedicine for clinical application as a combined therapy in the future.

Mycoendophytes as efficient synthesizers of bionanoparticles: nanoantimicrobials, mechanism, and cytotoxicity.

Mycoendophytes are the fungi that occur inside the plant tissues without exerting any negative impact on the host plant. They are most frequently isolated endophytes from the leaf, stem, and root tissues of various plants. Among all fungi, the mycoendophytes as biosynthesizer of noble metal nanoparticles (NPs) are less known. However, some reports showing efficient synthesis of metal nanoparticles, mainly silver nanoparticles and its remarkable antimicrobial activity against bacterial and fungal pathogens of humans and plants. The nanoparticles synthesized from mycoendophytes present stability, polydispersity, and biocompatibility. These are non-toxic to humans and environment, can be gained in an easy and cost-effective manner, have wide applicability and could be explored as promising candidates for a variety of biomedical, pharmaceutical, and agricultural applications. Mycogenic silver nanoparticles have also demonstrated cytotoxic activity against cancer cell lines and may prove to be a promising anticancer agent. The present review focuses on the biological synthesis of metal nanoparticles from mycoendophytes and their application in medicine. In addition, different mechanisms of biosynthesis and activity of nanoparticles on microbial cells, as well as toxicity of these mycogenic metal nanoparticles, have also been discussed.

Silver nanoparticles from Pilimelia columellifera subsp. pallida SL19 strain demonstrated antifungal activity against fungi causing superficial mycoses.

In this study, we present the in vitro antifungal activity of silver nanoparticles (AgNPs) synthesized from acidophilic actinobacterium Pilimelia columellifera subsp. pallida SL19 strain, alone and in combination with antibiotics viz., amphotericin B, fluconazole, and ketoconazole against pathogenic fungi, namely Candida albicans, Malassezia furfur, and Trichophyton erinacei. The minimum inhibitory concentration (MIC) and minimum biocidal concentration (MBC) of AgNPs against test fungi were evaluated. The fractional inhibitory concentration (FIC) index was determined to estimate antifungal activity of AgNPs combined with antibiotics. Antifungal activity of AgNPs varied among the tested fungal strains. M. furfur was found to be most sensitive to biogenic silver nanoparticles, followed by C. albicans and T. erinacei. The lowest MIC of AgNPs was noticed against M. furfur (16 µg ml-1 ). Synergistic effect was observed on C. albicans when AgNP were combined with amphotericin B and ketoconazole and on M. furfur with fluconazole and ketoconazole (FIC index of 0.5). Cytotoxic effect of AgNPs on HeLa and 3T3 cell lines was evaluated. The IC50 values were found to be 55 and 25 µg ml-1 , respectively. The present study indicates that silver nanoparticles from P. columellifera subsp. pallida SL19 strain have antifungal activity, both alone and in combination with antibiotics, and offer a valuable contribution to nanomedicine.