lipid-a and Bacteroides-Infections

Lipid A structural modifications can substantially impact the host's inflammatory response to bacterial LPS. Bacteroides fragilis, an opportunistic pathogen associated with life-threatening sepsis and intra-abdominal abscess formation, and Bacteroides thetaiotaomicron, a symbiont pivotal for proper host intestinal tissue development, both produce an immunostimulatory LPS comprised of penta-acylated lipid A. Under defined conditions, Porphyromonas gingivalis, an oral pathogen associated with periodontitis, also produces an LPS bearing a penta-acylated lipid A. However, this LPS preparation is 100-1000 times less potent than Bacteroides LPS in stimulating endothelial cells. We analyzed Bacteroides and P. gingivalis lipid A structures using MALDI-TOF MS and gas chromatography to determine the structural basis for this phenomenon. Even though both Bacteroides and P. gingivalis lipid A molecules are penta-acylated and mono-phosphorylated, subtle differences in mass and fatty acid content could account for the observed difference in LPS potency. This fatty acid heterogeneity is also responsible for the peak "clusters" observed in the mass spectra and obfuscates the correlation between LPS structure and immunostimulatory ability. Further, we show the difference in potency between Bacteroides and P. gingivalis LPS is TLR4-dependent. Altogether, the data suggest subtle changes in lipid A structure may profoundly impact the host's innate immune response.

Topics: Acylation; Bacteroidaceae Infections; Bacteroides; Bacteroides Infections; Cell Line; Humans; Immunity, Innate; Lipid A; Lipopolysaccharides; Porphyromonas gingivalis

The capsular polysaccharide of Bacteroides fragilis is most probably an important virulence factor as shown by its ability to protect against phagocytosis in in vitro studies, and by its abscess-promoting ability in experimental in vivo studies. Immunity against the capsular polysaccharide, either in the form of humoral antibodies or as cell-mediated immunity, can facilitate phagocytosis or prevent abscess formation. The capsular polysaccharides in two reference strains examined so far are complex in structure, and seem to be strain specific. The B. fragilis lipopolysaccharide has a relatively low endotoxic activity when compared to lipopolysaccharides from bacteria belonging to Enterobacteriaceae. Structurally the B. fragilis lipopolysaccharide has a relatively low molecular weight, and short polysaccharide chains similar to those found in lipopolysaccharides from rough mutants of Enterobacteriaceae or from capsulated bacteria such as Neisseria meningitidis and Haemophilus influenzae.

Topics: Abscess; Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacteroides fragilis; Bacteroides Infections; Humans; Lipid A; Lipopolysaccharides; Phagocytosis; Polysaccharides, Bacterial; Species Specificity; Virulence

Topics: Abdomen; Abscess; Anaerobiosis; Animals; Bacterial Toxins; Bacteroides fragilis; Bacteroides Infections; Clindamycin; Humans; Kanamycin; Lipid A; Metronidazole; Rats; Virulence