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Related Concept Videos

Formation of Lipopolysaccharides01:19

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Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
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Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
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The outermost layers of prokaryotic cells play a critical role in their survival, virulence, and interaction with the environment. These layers, often composed of polysaccharides, polypeptides, or proteins, form protective and adhesive structures that vary in organization and function.Capsules and Slime LayersCapsules are highly organized, tightly bound layers that firmly attach to the bacterial cell wall. Capsules are usually made of polysaccharides, though some are made of polypeptides. These...
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Purification and Visualization of Lipopolysaccharide from Gram-negative Bacteria by Hot Aqueous-phenol Extraction
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Lipopolysaccharide Domains Modulate Urovirulence.

Lizath M Aguiniga1, Ryan E Yaggie1, Anthony J Schaeffer1

  • 1Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Infection and Immunity
|August 17, 2016
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Lipopolysaccharide (LPS) structure in uropathogenic Escherichia coli (UPEC) is key to urinary tract infection (UTI) persistence and immune evasion. Modifying LPS domains impacts bacterial colonization, reservoir formation, and host immune responses, offering vaccine targets.

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Area of Science:

  • Microbiology and Immunology
  • Bacterial Pathogenesis
  • Vaccine Development

Background:

  • Uropathogenic Escherichia coli (UPEC) causes most urinary tract infections (UTIs), with rising antibiotic resistance necessitating novel prevention strategies like vaccines.
  • Previous research indicated UPEC's lipopolysaccharide (LPS) O-antigen influences immune responses, but the roles of other LPS domains remain less understood.
  • Understanding how LPS structure affects UPEC virulence and host immunity is crucial for developing effective UTI vaccines.

Purpose of the Study:

  • To investigate the contribution of specific lipopolysaccharide (LPS) domains (inner core, outer core, O-antigen) to urovirulence and immune modulation by UPEC.
  • To evaluate the impact of LPS structural modifications on UPEC adherence, colonization, reservoir formation, and host innate and adaptive immune responses in a murine UTI model.
  • To identify potential vaccine targets by elucidating the relationship between LPS structure and UPEC pathogenesis.

Main Methods:

  • Generated UPEC NU14 mutants with deletions in genes encoding LPS inner core (waaP, waaY, rfaQ), outer core (rfaG), and O-antigen (waaL, wzzE, wzyE) biosynthesis.
  • Assessed bacterial adherence to urothelial cells in vitro and colonization, bladder reservoir formation, and urinary myeloperoxidase levels in a murine UTI model.
  • Measured TLR4-dependent interleukin-33 (IL-33) production and quantified antigen-specific IgE and IgG1 antibody responses post-infection.

Main Results:

  • Deletions in waaP, waaY, and rfaG attenuated UPEC adherence in vitro, with the ΔrfaG mutant showing the most severe colonization defect in vivo.
  • Mutations in rfaG, waaL, wzzE, and wzyE abolished the ability of UPEC to form reservoirs in mouse bladders.
  • UPEC infection stimulated TLR4-dependent IL-33 production, which was reduced in infections with rfaG, waaL, wzzE, and wzyE mutants; ΔwaaP mutant infection led to increased IgE and IgG1.

Conclusions:

  • Lipopolysaccharide (LPS) structural components are critical determinants of UPEC's ability to colonize bladders acutely and establish persistent reservoirs.
  • Specific LPS domains differentially modulate innate (IL-33) and adaptive (IgE, IgG1) immune responses, influencing the host-pathogen interaction during UTI.
  • Targeting LPS structure offers a promising strategy for developing vaccines against UPEC and preventing recurrent urinary tract infections.