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Siddique, N.

Publications and source records attributed to Siddique, N..

2 recordsLinked to original sources
bioRxiv2025

Enterococcus faecium MBBL3 Exhibits Promising Probiotic Potential and Antimicrobial Efficacy Against Bovine Mastitis-Associated Escherichia coli and Klebsiella pneumoniae

Enterococcus faecium, a promising probiotic, combats pathogens, supports gut health, strengthens immunity, and provides a natural approach to address the escalating global challenge of antimicrobial resistance. This study aimed to investigate the genome of E. faecium MBBL3, isolated from healthy cow milk, to assess its probiotic potential and antimicrobial activity against pathogens causing bovine mastitis. The strain was analyzed through whole genome sequencing, along with in-vitro and in-silico assessments were conducted to determine its antimicrobial efficacy against bovine mastitis pathogens, Klebsiella pneumoniae MBBL2 (Kp MBBL2) and Escherichia coli MBBL4 (Ec MBBL4). The genome assembly and functional annotations uncovered many important probiotic traits in MBBL3, where genome comparison revealed its high genetic similarity with other Enterococcus strains. MBBL3 demonstrated the ability to ferment a wide range of carbohydrates and possessed 76 carbohydrate-active enzyme-related genes, including five key CAZy families namely GH73, GH18, CBM50, CE4, and AA10. It also possessed importance genes for bile salt and acid tolerance, stress resistance, and surface adhesion. Additionally, MBBL3 contained metabolite regions involved in the biosynthesis of antimicrobial compounds such as 2,4-DAPG, aborycin, enterocin NKR-5-3B, and sodorifen, and bacteriocin gene clusters for sactipeptides, Enterolysin_A, and UviB. Safety assessments indicated low pathogenic potential, while in-vitro assays demonstrated antibiotic susceptibility and suppressed the growth of Kp MBBL2 and Ec MBBL4, respectively. Its bacteriocin compound Enterolysin_A exhibited strong molecular interactions with virulence proteins of these mastitis pathogens. Therefore, the promising probiotic potential and antimicrobial efficacy of E. faecium MBBL3, especially against mastitis pathogens combined with its safety, position it as a valuable candidate for therapeutic applications. Key pointsO_LIE. faecium MBBL3 genosme showed high similarity with other species of this genera. C_LIO_LIGenetic makeup of MBBL3 revealed its ability to survival and adaptation in different niches including hosts gut. C_LIO_LIIn-vitro and in-silico study results, along with several genes linked to antimicrobials demonstrated its ability to combat against mastitis pathogens. C_LI

microbiology↗
bioRxiv2022

Molecular dynamics analysis of Superoxide Dismutase 1 mutations suggests decoupling between mechanisms underlying ALS onset and progression

Mutations in the superoxide dismutase 1 (SOD1) gene are the second most common known cause of ALS. SOD1 variants express high phenotypic variability and over 200 have been reported in people with ALS. Investigating how different SOD1 variants affect the protein dynamics might help in understanding their pathogenic mechanism and explaining their heterogeneous clinical presentation. It was previously proposed that variants can be broadly classified in two groups, wild-type like (WTL) and metal binding region (MBR) variants, based on their structural location and biophysical properties. MBR variants are associated with a loss of SOD1 enzymatic activity. In this study we used molecular dynamics and large clinical datasets to characterise the differences in the structural and dynamic behaviour of WTL and MBR variants with respect to the wild-type SOD1, and how such differences influence the ALS clinical phenotype. Our study identified marked structural differences, some of which are observed in both variant groups, while others are group specific. Moreover, applying graph theory to a network representation of the proteins, we identified differences in the intramolecular contacts of the two classes of variants. Finally, collecting clinical data of approximately 500 SOD1 ALS patients carrying variants from both classes, we showed that the survival time of patients carrying an MBR variant is generally longer (~6 years median difference, p < 0.001) with respect to patients with a WTL variant. In conclusion, our study highlights key differences in the dynamic behaviour of the WTL and MBR SOD1 variants, and wild-type SOD1 at an atomic and molecular level. We identified interesting structural features that could be further investigated to explain the associated phenotypic variability. Our results support the hypothesis of a decoupling between mechanisms of onset and progression of SOD1 ALS, and an involvement of loss-of-function of SOD1 with the disease progression.

neuroscience↗