New insights into the putative role of leucine-rich repeat proteins of Leptospira interrogans and their participation in host cell invasion: an in silico analysis DOI Creative Commons

Bruno B. Foltran,

João P. Gaspar,

Ilmini De Silva

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 12, 2024

Pathogenic Leptospira are spirochetes that cause leptospirosis, a worldwide zoonotic disease. Leptospirosis affects humans and animals, with approximately 1 million human infections 60,000 deaths per year. The diversity of leptospiral strains serovars allied to the fact pathogenesis is not yet fully understood, make development an effective vaccine against leptospirosis challenge. Outer membrane secreted proteins considered potential antigens since they play vital role in mediating interactions host molecules. Several domains or motifs have been reported participate infection process. Among them, leucine-rich repeat (LRR) highlighted as attractive multipurpose proteins, exhibiting broad spectrum ligands having putative bacterial pathogenesis. Indeed, genome annotation species pointed out LRR predominant pathogenic strains, feature corroborates this hypothesis. A few L. santarosai , borgpetersenii interrogans studied their possible virulence was proposed. Yet, mechanistic investigation performed. In review, comprehensive silico analysis 21 performed relation structure, function, dynamics virulent will contribute understanding key these underlying mechanisms infection.

Language: Английский

Experimental Approaches to Visualize Effector Protein Translocation During Host‐Pathogen Interactions DOI Creative Commons
Verena Nadin Fritsch, Michael Hensel

BioEssays, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

ABSTRACT Bacterial pathogens deliver effector proteins into host cells by deploying sophisticated secretion systems. This translocation during host‐pathogen interactions is a prerequisite for the manipulation of and organisms important pathogenesis. Analyses dynamics kinetics translocation, subcellular localization, cellular targets lead to understanding mode action function in interplay. review provides an overview biochemical genetic tools that have been developed study protein qualitatively or quantitatively. After introducing challenges analyses interaction, we describe various methods ranging from static visualization fixed dynamic live‐cell imaging translocation. We show main findings enabled approaches, emphasize advantages limitations methods, recent approaches allow real‐time tracking living on single molecule level, highlight open questions field be addressed application new methods.

Language: Английский

Citations

0
Salmonella Type III Secretion System Effectors DOI Open Access
Micah J. Worley

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2611 - 2611

Published: March 14, 2025

Salmonella is estimated to infect between 200 million and over 1 billion people per year. The exact number not known, as many cases go unreported. Integral the pathogenesis of Salmonella, well numerous other Gram-negative pathogens, its type III effectors. possesses two distinct secretion systems, encoded by pathogenicity island-1 island-2. Together, they secrete at least 49 effectors into host cells that are collectively responsible for virulence attributes this pathogen. These factors facilitate invasion cells, induce attenuate inflammation, change migratory properties infected phagocytes, among things. effects all on discussed.

Language: Английский

Citations

0
The Salmonella Effector SspH2 Facilitates Spatially Selective Ubiquitination of NOD1 to Enhance Inflammatory Signaling DOI
Cole Delyea,

Malcolm D. Forster,

Shu Luo

et al.

Biochemistry, Journal Year: 2024, Volume and Issue: 63(18), P. 2266 - 2279

Published: Aug. 27, 2024

As part of its pathogenesis,

Language: Английский

Citations

2
Engineered Ubiquitin Variants Mitigate Pathogenic Bacterial Ubiquitin Ligase Function DOI Creative Commons

Bradley E. Dubrule,

Ashley Wagner, Wei Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Abstract During infection some pathogenic gram-negative bacteria, such as Salmonella , manipulate the host ubiquitination system through delivery of secreted effectors known novel E3 ubiquitin ligases (NELs). Despite presence NELs amongst these well-studied bacterial species, their unique structure has limited tools that are available to probe molecular mechanisms and explore therapeutic potential. In this work, we report identification two high affinity engineered variants can modulate activity enterica serovar Typhimurium encoded NEL, SspH1. We show suppress SspH1-mediated toxicity phenotypes in Saccharomyces cerevisiae . Additionally, provide microscopic flow cytometric evidence is caused by interference with S. cell cycle progression be suppressed variants. vitro assays revealed increased amount chain formation. Interestingly, despite increase chains, observe a relative decrease formation K48-linked chains on its substrate, PKN1. Taken together our findings suggest SspH1 occurs an variant approach used identify modulators bacterially ligases. Author Summary Novel (NELs) family found various gram- negative bacteria. hijack vital signaling pathways aid invasion persistence. interacting protein highly conserved ubiquitin, they have distinct architecture eukaryotic enzymes. This combined indispensable role plays survival made hindering contribution infections difficult task. Here, applied engineering technology (Ubvs) for SspH1, -encoded NEL. Ubvs SspH1-meidated phenotype model also suppression without interfering signaling. Furthermore, demonstrate ability Ubv ultimately altering lysine linkages ubiquitination. To knowledge, first implemented previously untargetable bacterial-encoded

Language: Английский

Citations

0
New insights into the putative role of leucine-rich repeat proteins of Leptospira interrogans and their participation in host cell invasion: an in silico analysis DOI Creative Commons

Bruno B. Foltran,

João P. Gaspar,

Ilmini De Silva

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 12, 2024

Pathogenic Leptospira are spirochetes that cause leptospirosis, a worldwide zoonotic disease. Leptospirosis affects humans and animals, with approximately 1 million human infections 60,000 deaths per year. The diversity of leptospiral strains serovars allied to the fact pathogenesis is not yet fully understood, make development an effective vaccine against leptospirosis challenge. Outer membrane secreted proteins considered potential antigens since they play vital role in mediating interactions host molecules. Several domains or motifs have been reported participate infection process. Among them, leucine-rich repeat (LRR) highlighted as attractive multipurpose proteins, exhibiting broad spectrum ligands having putative bacterial pathogenesis. Indeed, genome annotation species pointed out LRR predominant pathogenic strains, feature corroborates this hypothesis. A few L. santarosai , borgpetersenii interrogans studied their possible virulence was proposed. Yet, mechanistic investigation performed. In review, comprehensive silico analysis 21 performed relation structure, function, dynamics virulent will contribute understanding key these underlying mechanisms infection.

Language: Английский

Citations

0