Open AccessIdentification of LpxL, a Late Acyltransferase of Francisella tularensis
Author(s) -
Molly K. McLendon,
Birgit Schilling,
Jason Hunt,
Michael A. Apicella,
Bradford W. Gibson
Publication year - 2007
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01288-06
Subject(s) - francisella tularensis , biology , acyltransferase , lipid a , complementation , lipopolysaccharide , bacterial outer membrane , mutant , proinflammatory cytokine , escherichia coli , microbiology and biotechnology , biochemistry , francisella , bacteria , enzyme , genetics , gene , inflammation , immunology , virulence
Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria, and the lipid A region of LPS mediates stimulation of the immune system in a structure-dependent manner. Unlike the LPS of many other gram-negative bacteria, the LPS ofFrancisella tularensis isolated from in vitro cultures is not proinflammatory. This observed lack of proinflammatory prowess may reflect structural features of the lipid A, such as the number and length of the acyl chains and the single-phosphate group. To better understand this phenotype, we have begun to elucidate LPS biosynthesis inF. tularensis . We present complementation, mutational, and chemical data demonstrating thatF. tularensis FTT0232c encodes a functional late acyltransferase enzyme with specificity similar to that of theEscherichia coli LpxL ortholog. Expression of this late acyltransferase complemented the temperature-sensitive and hypoacylated lipid A phenotypes of anE. coli lpxL mutant, expression of FTT0232c is increased during intracellular growth relative to that during in vitro growth, and finally, LPS obtained from a mutant ofF. tularensis lacking FTT0232c showed an abundant triacyl lipid A species after mass spectrometric analysis, consistent with the loss of an LpxL late acyltransferase.