TY - JOUR A1 - Azam, Hafiz Muhammad Husnain A1 - Rößling, Rosa Lise A1 - Geithe, Christiane A1 - Khan, Muhammad Moman A1 - Dinter, Franziska A1 - Hanack, Katja A1 - Prüß, Harald A1 - Husse, Britta A1 - Roggenbruck, Dirk A1 - Schierack, Peter A1 - Rödiger, Stefan T1 - MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases : a comprehensive review JF - Frontiers in Molecular Neuroscience N2 - Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells all indicative of disease progression before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Huntington’s disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or deubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies. KW - Neurodegenerative diseases KW - MicroRNA KW - Diagnostic tools KW - Therapeutic tools KW - Protein post-translational modifications KW - Nervendegeneration KW - Biomarker KW - miRNS KW - Diagnose KW - Posttranslationale Änderung Y1 - 2024 U6 - https://doi.org/10.3389/fnmol.2024.1386735 SN - 1662-5099 VL - 17 PB - Frontiers CY - Lausanne ER - TY - JOUR A1 - Khan, Muhammad Moman A1 - Mushtaq, Muhammad Ahmed A1 - Abbas, Nayyar A1 - Fatima, Fariha A1 - Gibbon, Marjorie J. A1 - Schierack, Peter A1 - Mohsin, Mashkoor T1 - Occurrence, antimicrobial resistance and genomic features of Klebsiella pneumoniae from broiler chicken in Faisalabad, Pakistan JF - Frontiers in Veterinary Science N2 - The dissemination of antimicrobial resistance (AMR) in critical priority pathogens is a significant threat. Non-clinical reservoirs of AMR, such as agriculture and food production facilities, may contribute to the transmission of clinically relevant pathogens such as multidrug-resistant (MDR) Klebsiella pneumoniae. There is currently very limited knowledge regarding the population structure and genomic diversity of K. pneumoniae in poultry production in Pakistan. We explored healthy broilers in a commercial farm from Faisalabad, Pakistan, and identified six K. pneumoniae strains from 100 broiler birds. We characterized the strains, determining clonality, virulence and antimicrobial resistance genes using next generation sequencing. The evaluation of antimicrobial susceptibility revealed that all the strains were MDR. Genomic analysis showed that 3/6 strains belonged to ST152, harbouring acquired resistance aminoglycosides [aadA2, aph(4′)-Ia], β-lactams (blaSHV-187, blaLAP2), fosfomycin (fosA6), tetracycline (tetA), trimethoprim (dfrA12), quinolone (qnrS1), sulphonamides (sul2) and phenicol (floR). All the strains harboured the efflux pump genes oqxA, oqxB, emrR, kpnG, kpnH, kpnF, baeR, mtdB and mtdC. All six strains encoded identical virulence profiles possessing six genes, i.e., ureA, iutA, entB, allS, fimH and mrkD. Phylogenomic analysis of the dominant sequence type (ST152) present in our dataset with publicly available genomes showed that the isolates clustered to strains mainly from human sources and could pose a potential threat to food safety and public health. The combination of these findings with antimicrobial use data would allow a better understanding of the selective pressures that may be driving the spread of AMR. This is the first report of MDR K. pneumoniae isolated from broiler hens in Pakistan, and the finding suggests that routine surveillance of WHO critical priority pathogens in such settings would be beneficial to the development of effective control strategies to reduce AMR. KW - Antimicrobial resistance KW - Poultry KW - Genomics KW - K. pneumoniae KW - Sequence type Y1 - 2024 U6 - https://doi.org/10.3389/fvets.2024.1433124 SN - 2297-1769 VL - 11 PB - Frontiers CY - Lausanne ER - TY - JOUR A1 - Khan, Muhammad Moman A1 - Sidorczuk, Katarzyna A1 - Becker, Juliane A1 - Aleksandrowicz, Adrianna A1 - Baraniewicz, Karolina A1 - Ludwig, Christina A1 - Ali, Aamir A1 - Kingsley, Robert A. A1 - Schierack, Peter A1 - Kolenda, Rafał T1 - Characterization of clumpy adhesion of Escherichia coli to human cells and associated factors influencing antibiotic sensitivity JF - Microbiology Spectrum N2 - Escherichia coli intestinal infection pathotypes are characterized by distinct adhesion patterns, including the recently described clumpy adhesion phenotype. Here, we identify and characterize the genetic factors contributing to the clumpy adhesion of E. coli strain 4972. In this strain, the transcriptome and proteome of adhered bacteria were found to be distinct from planktonic bacteria in the supernatant. A total of 622 genes in the transcriptome were differentially expressed in bacteria present in clumps relative to the planktonic bacteria. Seven genes targeted for disruption had variable distribution in different pathotypes and non-pathogenic E. coli, with the pilV and spnT genes being the least frequent or absent from most groups. Deletion (Δ) of five differentially expressed genes, flgH, ffp, pilV, spnT, and yggT, affected motility, adhesion, or antibiotic stress. ΔflgH exhibited 80% decrease and ΔyggT depicted 184% increase in adhesion, and upon complementation, adhesion was significantly reduced to 13%. ΔflgH lost motility and was regenerated when complemented, whereas Δffp had significantly increased motility, and reintroduction of the same gene reduced it to the wild-type level. The clumps produced by Δffp and ΔspnT were more resistant and protected the bacteria, with ΔspnT showing the best clump formation in terms of ampicillin stress protection. ΔyggT had the lowest tolerance to gentamicin, where the antibiotic stress completely eliminated the bacteria. Overall, we were able to investigate the influence of clump formation on cell surface adhesion and antimicrobial tolerance, with the contribution of several factors crucial to clump formation on susceptibility to the selected antibiotics. KW - Escherichia coli KW - Clumpy adhesion KW - Motility KW - Antibiotic tolerance KW - Stress KW - Escherichia coli KW - Zelladhäsion KW - Phänotyp KW - Genanalyse Y1 - 2024 U6 - https://doi.org/10.1128/spectrum.02606-23 SN - 2165-0497 VL - 12 IS - 5 PB - American Society for Microbiology (ASM) CY - Washington, DC ER -