Publications by authors named "Pravil Pokharel"

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the specific destruction of insulin-producing beta cells in the pancreas by the immune system, including CD4 cells which orchestrate the attack and CD8 cells which directly destroy the beta cells, resulting in the loss of glucose homeostasis.

Scope Of Review: This comprehensive document delves into the complex interplay between the immune system and beta cells, aiming to shed light on the mechanisms driving their destruction in T1D. Insights into the genetic predisposition, environmental triggers, and autoimmune responses provide a foundation for understanding the autoimmune attack on beta cells.

View Article and Find Full Text PDF

In , the disaccharide trehalose can be metabolized as a carbon source or be accumulated as an osmoprotectant under osmotic stress. In hypertonic environments, accumulates trehalose in the cell by synthesis from glucose mediated by the cytosolic enzymes OtsA and OtsB. Trehalose in the periplasm can be hydrolyzed into glucose by the periplasmic trehalase TreA.

View Article and Find Full Text PDF

In this review, we explore the complex interplay between the immune system and pancreatic β cells in the context of type 1 diabetes (T1D). While T1D is predominantly considered a T-cell-mediated autoimmune disease, the inability of human leukocyte antigen (HLA)-risk alleles alone to explain disease development suggests a role for β cells in initiating and/or propagating disease. This review delves into the vulnerability of β cells, emphasizing their susceptibility to endoplasmic reticulum (ER) stress and protein modifications, which may give rise to neoantigens.

View Article and Find Full Text PDF

() is a gram-negative bacillus and resident of the normal intestinal microbiota. However, some strains can cause diseases in humans, other mammals and birds ranging from intestinal infections, for example, diarrhea and dysentery, to extraintestinal infections, such as urinary tract infections, respiratory tract infections, meningitis, and sepsis. In terms of morbidity and mortality, pathogenic has a great impact on public health, with an economic cost of several billion dollars annually worldwide.

View Article and Find Full Text PDF

Fimbrial adhesins promote bacterial adherence and biofilm formation. Sequencing of avian pathogenic Escherichia coli (APEC) strain QT598 identified new fimbriae belonging to the π group, which we named PL (P-like) fimbriae since the genetic organization and sequence are similar to those of P and related fimbriae. Genes encoding PL fimbriae located on IncF plasmids are present in diverse E.

View Article and Find Full Text PDF

Urinary tract infections (UTIs) are a common bacterial infectious disease in humans, and strains of uropathogenic Escherichia coli (UPEC) are the most frequent cause of UTIs. During infection, UPEC must cope with a variety of stressful conditions in the urinary tract. Here, we demonstrate that the small RNA (sRNA) RyfA of UPEC strains is required for resistance to oxidative and osmotic stresses.

View Article and Find Full Text PDF

Urinary tract infections (UTIs) affect more than 150 million people, with a cost of over 3.5 billion dollars, each year. is associated with 70-80% of UTIs.

View Article and Find Full Text PDF

TagB, TagC (andem utotransporter enes and ), and Sha (erine-protease emagglutinin utotransporter) are recently described members of the SPATE (serine protease autotransporters of ) family. These SPATEs can cause cytopathic effects on bladder cells and contribute to urinary tract infection in a mouse model. Bladder epithelial cells form an important barrier in the urinary tract.

View Article and Find Full Text PDF

Autotransporters are secreted proteins with multiple functions produced by a variety of Gram-negative bacteria. In , a subgroup of these autotransporters are the SPATEs (serine protease autotransporters of ). SPATEs play a crucial role in survival and virulence of pathogens such as and spp.

View Article and Find Full Text PDF

Urinary tract infections (UTIs) are common bacterial infections and the vast majority of UTIs are caused by extraintestinal pathogenic (ExPEC) strains referred to as uropathogenic (UPEC). Successful colonization of the human urinary tract by UPEC is mediated by secreted or surface exposed virulence factors-toxins, iron transport systems, and adhesins, such as type 1 fimbriae (pili). To identify factors involved in the expression of type 1 fimbriae, we constructed a chromosomal transcriptional reporter consisting of under the control of the fimbrial promoter region, and this construct was inserted into the reference UPEC strain CFT073 genome at the Tn7 site.

View Article and Find Full Text PDF

Serine protease autotransporters of (SPATEs) are secreted proteins that contribute to virulence and function as proteases, toxins, adhesins, and/or immunomodulators. An extra-intestinal pathogenic (ExPEC) O1:K1 strain, QT598, isolated from a turkey, was shown to contain , and three uncharacterized SPATE-encoding genes. Uncharacterized SPATEs: Sha (erine-protease emagglutinin utotransporter), TagB and TagC (andem utotransporter enes and ) were tested for activities including hemagglutination, autoaggregation, and cytotoxicity when expressed in K-12.

View Article and Find Full Text PDF