Target intelligence / Profile preview

Lipopolysaccharide O-antigen (Pseudomonas aeruginosa) (LPS O-antigen)

Target
LPS O-antigen
Molecular classification
Polysaccharide, Bacterial surface antigen, Glycan
01

Overview

The Lipopolysaccharide (LPS) O-antigen is the outermost component of the Gram-negative bacterium Pseudomonas aeruginosa, extending from the cell surface into the external environment. It consists of repeating polysaccharide units that are highly variable, defining the various serotypes of the species and playing a crucial role in bacterial survival within the host. The O-antigen serves as a protective shield against the host's innate immune system, specifically preventing the assembly of the complement membrane attack complex and resisting opsonization. In clinical medicine, it is a major target for the development of passive immunotherapies, such as monoclonal antibodies, and active vaccines intended to treat or prevent multidrug-resistant infections. However, the high degree of structural diversity among strains and the tendency of P. aeruginosa to lose its O-antigen during chronic infections (transitioning to a 'rough' phenotype) pose significant challenges for universal therapeutic targeting.

Other names
O-specific antigenOSAO-side chainO-polysaccharideB-band lipopolysaccharideCommon polysaccharide antigen (A-band)Endotoxin (O-antigen component)
02

Mechanism of action

Monoclonal antibodies targeting the O-antigen promote opsonophagocytic killing by host immune cells and neutralize the endotoxic effects of LPS. Some antibiotics and antimicrobial peptides interact with the LPS layer to disrupt the outer membrane integrity, leading to cell lysis. Vaccines aim to induce long-term humoral immunity by generating antibodies specific to the O-antigen serotypes.

03

Biological functions

Structural integrity of the outer membraneProtection against complement-mediated killingEvasion of phagocytosisPermeability barrier against antibioticsBacterial adhesionBiofilm formation
04

Disease associations

InfectionSepsisCystic fibrosis-associated lung infectionVentilator-associated pneumoniaBurn wound infection
05

Safety considerations

Jarisch-Herxheimer-like reaction due to rapid endotoxin releaseSerotype specificity limiting broad-spectrum efficacySelection for 'rough' mutants (strains lacking O-antigen)Potential for cross-reactivity with host glycans
06

Interacting drugs

Panobacumab (AR-101)

4 more in the full profile.

07

Biomarkers

O-antigen serotype (e.g., O11, O1, O6)Serum LPS levelsAnti-LPS antibody titers

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