Search bioRxiv⌕ Search

Biology subjects

Fertig, T. E.

Publications and source records attributed to Fertig, T. E..

2 recordsLinked to original sources

Characterization of two lytic bacteriophages isolated from urban surface water in Romania targeting multidrug-resistant Escherichia coli

BackgroundThe global rise of multidrug-resistant (MDR) bacteria represents a critical public health threat, and Romania ranks amongst the most affected countries in Europe. As conventional therapy increasingly fails, bacteriophage therapy has re-emerged as a promising alternative to antibiotics. Urban rivers, contaminated with resistant bacterial strains, represent an underexplored and accessible reservoir for the isolation of lytic phages with therapeutic potential. MethodsTwo bacteriophages, 17M_Ec17_D and 22C_Ec22_D, were isolated from the Dambovita River, Bucharest, Romania, using MDR E. coli as host bacteria. Phage characterization included plaque morphology, transmission electron microscopy, and host range assessment by spot assay against 30 MDR E. coli isolates. Whole genome sequencing was performed on Illumina MiSeq and Oxford Nanopore Technologies MinION platforms, followed by bioinformatic analysis including taxonomic classification, lifestyle prediction, and functional annotation. ResultsBoth phages formed clear plaques and were classified as Kayfunavirus (17M_Ec17_D, Podoviridae-like) and Kagunavirus (22C_Ec22_D, Siphoviridae-like) with nucleotide similarities of 89.2% and 71.4% to their closest relatives, respectively, suggesting both are candidates for novel species. Host range analysis revealed lytic activity against 13% and 10% of tested MDR isolates, with complementary infection profiles. Genomic analysis confirmed a strictly lytic lifestyle for both phages, supported by the presence of holin and spanin genes and the absence of lysogenic modules, antibiotic resistance genes, and virulence factors. ConclusionsTo the best of our knowledge, this is the first study conducted in Romania to isolate and genomically characterize lytic bacteriophages targeting MDR E. coli. The characterized phages represent safe therapeutic candidates whose complementary host ranges suggest potential application as part of phage cocktail to broaden antimicrobial coverage against MDR infections.

microbiology↗

In situ evidence that mast cells release mutant NLRP1 in keratoacanthomas from multiple self-healing palmoplantar carcinoma

NLRP1 is an inflammasome sensor protein expressed in barrier tissues of humans. Its activation in response to microbes or cellular stress triggers a cascade of molecular events, leading up to IL1{beta}-driven inflammation and pyroptosis. Rare germline mutations of NLRP1 cause its persistent activation, resulting in autoinflammatory syndromes. Multiple self-healing palmoplantar carcinoma (MSPC) is one such syndrome, characterized by the appearance of recurrent keratoacanthomas (KAs) on the palms and soles. Here, we aimed to compare the subcellular localization of mutant NLRP1 in MSPC-associated lesions, to wild-type NLRP1 in non-MSPC KAs and in skin from healthy donors. Using mass spectrometry, immunohistochemistry and immunoelectron tomography, we found that NLRP1 localized to mast cell (MC) granules in all samples, a novel finding which implicates MCs in NLRP1-associated responses in human skin. Moreover, we found that MCs expressing the A66V pathogenic variant of NLRP1 overpopulated MSPC-KAs, infiltrated the epidermis and degranulated, a behavior not seen in other lesions from this study. The released granules had the highest NLRP1 protein content and also contained NLRP3 and IL1{beta}, indicating coexistence of inflammasome pathways within MCs. Taken together, our findings establish cutaneous MCs as a NLRP1 reservoir in health and disease, opening a new area of research in NLRP1-related syndromes.

immunology↗