Demarco De Hormaeche R

Ellis CD

Khan CMA

Lindner B

Zahringer U

LPS is a fundamental constituent of the outer membrane of all Gram-negative bacteria, and the lipid A domain plays a central role in the induction of inflammatory responses. We identified genes of the Neisseria gonorrhoeae lipid A biosynthetic pathway by searching the complete gonococcal genome sequence with sequences of known enzymes from other species. The lpxLII gene was disrupted by an insertion-deletion in an attenuated aroA mutant of the gonococcal strain MS11. Lipopolysaccharide (LPS) and lipid A analysis demonstrated that the lpxLII mutant had synthesized an altered LPS molecule lacking a single lauric fatty acid residue in the GlcN II of the lipid A backbone. LPS of the lpxLII mutant had a markedly reduced ability to induce the proinflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-8 from human macrophages and IL-8 from polymorphonuclear cells. This study demonstrates that the lpxLII gene in gonococci encodes for a late-functioning lauroyl acyl transferase that adds a lauric acid at position 2′ in the lipid A backbone. The presence of lauric acid at such a position appears to be crucial for the induction of full inflammatory responses by N. gonorrhoeae LPS

Newcastle University E-Prints

The <em>Neisseria gonorrhoeae lpxLII</em> gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses

The <em>Neisseria gonorrhoeae lpxLII</em> gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses

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