The Neisseria gonorrhoeae lpxLII 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

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.