ArticleMolecular oral microbiology2011
Aggregatibacter actinomycetemcomitans leukotoxin is post-translationally modified by addition of either saturated or hydroxylated fatty acyl chains.
Article in Molecular oral microbiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- Leukotoxin A Production and Release by JP2 and Non-JP2 GenotypePathogens (Basel, Switzerland) · 2024Article
- Membrane Interaction Characteristics of the RTX Toxins and the Cholesterol-Dependence of Their Cytolytic/Cytotoxic Activity.International journal of molecular sciences · 2024Review
- Heterologously secreted MbxA from Moraxella bovis induces a membrane blebbing response of the human host cell.Scientific reports · 2022Article
- Review
- Leukotoxin (LtxA/Leukothera) induces ATP expulsion via pannexin-1 channels and subsequent cell death in malignant lymphocytes.Scientific reports · 2021Article
- Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti-toxin therapeutics.Molecular oral microbiology · 2020Review
- Review
- Aggregatibacter actinomycetemcomitans Leukotoxin (LtxA) Requires Death Receptor Fas, in Addition to LFA-1, To Trigger Cell Death in T Lymphocytes.Infection and immunity · 2019Article
- Aggregatibacter actinomycetemcomitans leukotoxin causes activation of lymphocyte function-associated antigen 1.Cellular microbiology · 2019Article
- Cytotoxic activity of Kingella kingae RtxA toxin depends on post-translational acylation of lysine residues and cholesterol binding.Emerging microbes & infections · 2018Article
- Generation of a recombinant Aggregatibacter actinomycetemcomitans RTX toxin in Escherichia coli.Gene · 2018Article
- Receptor-Based Peptides for Inhibition of Leukotoxin Activity.ACS infectious diseases · 2018Article
- Membrane localization of the Repeats-in-Toxin (RTX) Leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans.PloS one · 2018Article
- S- to N-Palmitoyl Transfer During Proteomic Sample Preparation.Journal of the American Society for Mass Spectrometry · 2016Article
- Inhibition of LtxA toxicity by blocking cholesterol binding with peptides.Molecular oral microbiology · 2016Article
- Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep.Infection and immunity · 2015Article
- LFA-1-targeting Leukotoxin (LtxA; Leukothera®) causes lymphoma tumor regression in a humanized mouse model and requires caspase-8 and Fas to kill malignant lymphocytes.Leukemia research · 2015Article
- Probing bacterial metabolism during infection using high-resolution transcriptomics.Journal of bacteriology · 2013Article
- G protein-coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor-promoted centrosomal separation.Molecular biology of the cell · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Aggregatibacter actinomycetemcomitans, a common inhabitant of the human upper aerodigestive tract, produces a repeat in toxin (RTX), leukotoxin (LtxA). The LtxA is transcribed as a 114-kDa inactive protoxin with activation being achieved by attachment of short chain fatty acyl groups to internal lysine residues. Methyl esters of LtxA that were isolated from A. actinomycetemcomitans strains JP2 and HK1651 and subjected to gas chromatography/mass spectrometry contained palmitoyl (C16:0, 27-29%) and palmitolyl (C16:1 cis Δ9, 43-44%) fatty acyl groups with smaller quantities of myristic (C14:0, 14%) and stearic (C18:0, 12-14%) fatty acids. Liquid chromatography/mass spectrometry of tryptic peptides from acylated and unacylated recombinant LtxA confirmed that Lys(562) and Lys(687) are the sites of acyl group attachment. During analysis of recombinant LtxA peptides, we observed peptide spectra that were not observed as part of the RTX acylation schemes of either Escherichia coliα-hemolysin or Bordetella pertussis cyclolysin. Mass calculations of these spectra suggested that LtxA was also modified by the addition of monohydroxylated forms of C14 and C16 acyl groups. Multiple reaction monitoring mass spectrometry identified hydroxymyristic and hydroxypalmitic acids in wild-type LtxA methyl esters. Single or tandem replacement of Lys(562) and Lys(687) with Arg blocks acylation, resulting in a >75% decrease in cytotoxicity when compared with wild-type toxin, suggesting that these post-translational modifications are playing a critical role in LtxA-mediated target cell cytotoxicity.
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