Conventional cotton fabrics used in hospitals and sportswear are prone to bacterial adhesion and proliferation, complicating hygiene and posing a health hazard. Modified cotton materials are in demand in healthcare and the sport industries due to the ability to impart various properties, including antipathogenic activity. In this work, cotton fabrics coated with hybrid boron nitride_zinc oxide (BN_ZnO) and diethylenetriamine (DETA)-modified BN_ZnO nanoparticles (BN_ZnO_DETA NPs) were studied. The presence of an amino layer on the BN_ZnO NP surface made it possible to deposit approximately twice as many BN_ZnO NPs, as well as to increase their stability (expressed as % of retained NPs) on the textile surface after immersion in water for 24 h from 63.6 to 92.6 %. Surface-modified textile materials demonstrated high hydrophobicity and associated increased resistance to various liquid contaminants (ink, soy sauce, and tomato juice), as well as self-cleaning ability under the influence of UV radiation. The pathogens (hospital E. coli U20 and S. aureus MW2 strains) were complete eliminated by fabric after 24 h of cultivation with the samples (BN_ZnO) and (BN_ZnO) + diethylenetriamine (DETA)) with bacteria. In vivo tests demonstrated the safety of BN_ZnO_DETA NPs-modified samples. Their contact with skin did not cause inflammation, and histological examination showed the structure of normal skin.
The rise in antimicrobial resistance represents a significant challenge to global health. The reason partially lies in an inappropriate use of conventional antibiotics and the subsequent rapid spread of multidrug-resistant pathogen strains. This emergency requires an urgent search for conceptually new antimicrobial agents. A viable alternative to conventional antibiotics is antimicrobial peptides (AMPs), which are ribosomally synthesized molecules with considerable potential as next-generation anti-infectious therapeutics. Previously, we have reported on the β-hairpin peptide Ap9, an analog of abarenicin from the marine polychaeta Abarenicola pacifica, with potent activity against key Gram-negative pathogens. Here, it is shown that Ap9 acts in a manner resembling polymyxin B, namely via interaction with lipopolysaccharide (LPS), and retains its activity against polymyxin-resistant isolates without observed cross-resistance, and causes insignificant damage in cytoplasmic membrane at bactericidal concentrations. NMR spectroscopy reveals that LPS binding induces a conformational rearrangement of Ap9, its dimer formation, and local structural remodeling of the peptide region (residues 8-12) into 310-helix. Bacterial resistance to Ap9 was found to be relatively low with a reduced susceptibility associated with infrequent genetic alterations, such as the mutation in lptD or the deletion in mlaA. Furthermore, Ap9 demonstrates a favorable tolerability, a wider therapeutic window than that of polymyxin B, and a sufficiently long half-life through the systemic use, as well as in vivo efficacy in murine models of Gram-negative infections, including sepsis caused by the mcr-1-harboring Escherichia coli strain. The obtained results point to Ap9 as a promising candidate for further preclinical studies aimed at development of an alternative to polymyxins.
Bacillus anthracis has three main virulence factors: an extracellular capsule and two binary toxins (lethal toxin—consists of a lethal factor and a protective antigen, and edema toxin—consists of an edema factor and a protective antigen). In the Russian Federation, the epidemiological situation regarding anthrax infection remains unfavorable. In the late stages of an anthrax infection, antibiotic therapy becomes ineffective and the patient dies within 24 h as a large amount of lethal toxin accumulates in the patient’s blood. Antibodies capable of neutralising lethal toxin (LT) can be an effective treatment for these patients. The objective of the study was to construct a chimeric monoclonal antibody targeting the protective antigen of the LT and to elucidate its mechanism of toxin neutralization. In this work, a chimeric monoclonal antibody (xi1E10) directed against the protective antigen was successfully produced. Both in vitro and in vivo experiments demonstrated the capacity of xi1E10 to neutralize lethal toxin. Confocal microscopy revealed that xi1E10 effectively suppresses the formation of a functional pore, thereby blocking the translocation of the lethal factor into the cytosol. These findings indicate that the monoclonal antibody xi1E10 represents a promising candidate for the development of a therapeutic drug.
Francisella tularensis is a bacterial pathogen that can contaminate drinking water and food products, causing tularemia - a severe zoonotic disease that affects both humans and animals. This infection is dangerous to human health and may be fatal without diagnosis and treatment. Therefore, rapid, sensitive, and selective detection of this microorganism is in high demand for clinical diagnostics, environmental monitoring, and ensuring food safety. This study presents the development of immunochromatographic (lateral flow) tests for revealing F. tularensis cells in natural and drinking water samples. A special feature of the test system is catalytically active Au@Pt nanoparticles (a peroxidase-like nanozyme) used as a label for specific antibodies. Au@Pt nanozyme can catalyze the oxidation of the peroxidase substrate, followed by the formation of a colored product, which amplifies the colorimetric signal on the test strip and significantly improves detection sensitivity. The tests allow for the detection of F. tularensis cells in concentrations down to 102-103 cells per mL, depending on the strain, with visual result assessment. The application of Au@Pt nanozyme decreased the detection limits by 321-9600 times compared to gold nanoparticles commonly used in immunochromatography. The assay duration is 14 min, including the catalytic enhancement step. Monoclonal antibodies against bacterial lipopolysaccharide provide selective detection of virulent strains, excluding cross-reactions with non-pathogenic strains of F. tularensis and other microorganisms that may also contaminate water sources. The effective testing of natural and tap water samples conducted with no preliminary sample preparation has proven the relevance of the developed approach.
Antimicrobial resistance (AMR) poses a critical threat to global health, particularly in intensive care units, where vulnerable patients are frequently exposed to multidrug-resistant microorganisms. The human gut microbiome serves as a key reservoir for AMR genes, which can disseminate to other body sites, including the lungs, especially during severe illness. We applied Hi-C metagenomics to stool samples from 11 critically ill COVID-19 patients and analyzed microbial isolates from their lungs to investigate intra-host transmission of AMR genes. Plasmid-resolved microbial interaction networks revealed AMR gene sharing across 13 bacterial genera, primarily from Firmicutes and Proteobacteria, with evidence of plasmid-mediated transfer across phylum boundaries and between gut and lung compartments. Notably, we identified genetically identical Klebsiella pneumoniae strains colonizing both the gut and lungs of a single patient, as well as shared plasmids carrying qnrS-1 and blaCTX-M-231 resistance genes between gut Escherichia coli and lung K. pneumoniae. In addition to bacterial pathogens, Candida yeast species isolated from both niches harbored resistance genes to multiple antifungal classes, including azoles. These findings underscore the dynamic, cross-compartmental nature of AMR dissemination within the human body and highlight the importance of integrative surveillance strategies to control resistance in clinical settings.IMPORTANCEWhile COVID-19 itself caused severe illness, many deaths were ultimately due to secondary microbial infections-often worsened by antibiotic resistance. Plasmids, which shuttle resistance genes between bacterial species, are key players in their spread, yet their roles in transmission, especially across body sites such as the gut and lungs, are to be elucidated. The use of Hi-C metagenomics allowed us to map bacterium-plasmid links in the guts of severe COVID-19 patients and reconstruct high-quality genomes of opportunistic fungi. Comparing these with lung-derived isolate genomes, we gained insight into possible intra-host dissemination routes of resistance genes. Preparing for future pandemics will require not only rapid pathogen detection but also tools to monitor microbiome health and resistance dynamics, and understanding how treatments and microbial imbalances shape infection risks.
