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PMID:21357723
| Citation |
Wong, SM, St Michael, F, Cox, A, Ram, S and Akerley, BJ (2011) ArcA-regulated glycosyltransferase lic2B promotes complement evasion and pathogenesis of nontypeable Haemophilus influenzae. Infect. Immun. 79:1971-83 |
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| Abstract |
Signaling mechanisms used by Haemophilus influenzae to adapt to conditions it encounters during stages of infection and pathogenesis are not well understood. The ArcAB two-component signal transduction system controls gene expression in response to respiratory conditions of growth and contributes to resistance to bactericidal effects of serum and to bloodstream infection by H. influenzae. We show that ArcA of nontypeable H. influenzae (NTHI) activates expression of a glycosyltransferase gene, lic2B. Structural comparison of the lipooligosaccharide (LOS) of a lic2B mutant to that of the wild-type strain NT127 revealed that lic2B is required for addition of a galactose residue to the LOS outer core. The lic2B gene was crucial for optimal survival of NTHI in a mouse model of bacteremia and for evasion of serum complement. The results demonstrate that ArcA, which controls cellular metabolism in response to environmental reduction and oxidation (redox) conditions, also coordinately controls genes that are critical for immune evasion, providing evidence that NTHI integrates redox signals to regulate specific countermeasures against host defense. |
| Links |
PubMed PMC3088160 Online version:10.1128/IAI.01269-10 |
| Keywords |
Animals; Bacterial Proteins/genetics; Bacterial Proteins/immunology; Blotting, Western; Cell Separation; Complement System Proteins/immunology; Flow Cytometry; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Haemophilus Infections/immunology; Haemophilus influenzae/genetics; Haemophilus influenzae/immunology; Haemophilus influenzae/pathogenicity; Humans; Immune Evasion/genetics; Lipopolysaccharides/chemistry; Lipopolysaccharides/immunology; Mice; Oxidation-Reduction; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0016757: transferase activity, transferring glycosyl groups |
ECO:0000315: |
F |
Table 3&4. Examination of carbohydrate modification by negative-ion CE-ES-MS. Comparison of lic2B mutant to wildtype reveals structural dissimilarities. Sugar composition analysis indicated that the lic2B mutant LOS was devoid of galactose in its outer core, in contrast to that of the wildtype. |
complete | ||||
| GO:0009103: lipopolysaccharide biosynthetic process |
ECO:0000255: |
UniProtKB: |
P |
Figure 3: with two independently derived clones for each mutation, lic2B and lic2C mutants yielded marked and statistically significant decreases in survival compared to the wild type |
complete | |||
|
enables |
GO:0016757: transferase activity, transferring glycosyl groups |
ECO:0000315: mutant phenotype evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
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