1887

Abstract

is an opportunistic pathogen that in the environment colonizes biofilms and replicates within amoebae. The bacteria employ the intracellular multiplication/defective organelle trafficking (Icm/Dot) type IV secretion system to grow intracellularly in a specific vacuole. Using as a host cell, we have previously identified ( cytotoxic suppressor), a paralogue of the lipid A disaccharide synthase , as a cytotoxic factor of . A bioinformatic analysis of the genome revealed that is unique in harbouring two paralogues of and two and three paralogues of the lipid A biosynthesis acyltransferases and , respectively. () forms a transcriptional unit with , encoding a putative UDP-GlcNAc oxidase in the biosynthetic pathway leading to 3-aminoglucosamine analogues of lipid A. clusters with , and paralogues, encoding secondary acyltransferases. / and were found to partially complement the growth defect of an conditional mutant strain, indicating that both corresponding enzymes possess lipid A disaccharide synthase activity. The two paralogues are not functionally equivalent, since expression of / but not in an mutant is cytotoxic for , and LPS purified from the two strains triggers CD14-dependent tumour necrosis factor (TNF) production by macrophages with a different potency. The and paralogues are expressed under various growth conditions, including broth, biofilms and in . While the flagellar gene is mainly expressed in late stationary phase, the and paralogues are preferentially expressed in the exponential and early stationary phases. Upon exposure to hypotonic stress and nutrient deprivation, , and to a lesser extent /, is upregulated. The differential regulation of or paralogues in response to changing environmental conditions might allow to adapt its lipid A structure.

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2007-11-01
2020-10-26
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