Decreased Infectivity despite Unaltered C3 Binding by a ΔhbhAMutant ofMycobacterium tuberculosis
| Autor: | Eliud Sepulveda, Steven J. Norris, Stacey L. Mueller-Ortiz, Chinnaswamy Jagannath, Margaret Olsen, Audrey Wanger |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Tuberculosis
Transcription Genetic Molecular Sequence Data Immunology Mutant Microbiology Bacterial Adhesion Cell Line Mycobacterium tuberculosis Mice Bacterial Proteins Phagocytosis medicine Animals Humans Amino Acid Sequence Tuberculosis Pulmonary Southern blot Infectivity chemistry.chemical_classification Host Response and Inflammation biology Macrophages Binding protein Membrane Proteins Complement C3 medicine.disease biology.organism_classification Mice Inbred C57BL Infectious Diseases chemistry Cell culture Female Parasitology Glycoprotein Sequence Alignment Gene Deletion |
| Zdroj: | Infection and Immunity. 70:6751-6760 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.70.12.6751-6760.2002 |
| Popis: | HbhA ofMycobacterium tuberculosisis a multifunctional binding protein, binding to both sulfated sugars such as heparin and to human complement component C3. HbhA may therefore interact with host molecules and/or host cells duringM. tuberculosisinfection and play a role in the pathogenesis of this bacterium. The purpose of this study was to use allelic exchange to create anM. tuberculosisstrain deficient in expression of HbhA to determine whether this protein's C3-binding activity plays a role in the pathogenesis ofM. tuberculosis. An in-frame, 576-bp unmarked deletion in thehbhAgene was created usingsacBas a counterselectable marker. Southern blotting and PCR analyses confirmed deletion ofhbhAin the ΔhbhAmutant. The ΔhbhAmutant strain grew at a rate similar to that of the parent in broth culture and in J774.A1 murine macrophage-like cells but was deficient in growth compared to the parent strain in the lungs, liver, and spleen of infected mice. In addition, the ΔhbhAmutation did not reduce binding ofM. tuberculosisto human C3 or to J774.A1 cells in the presence or absence of serum, suggesting that in the absence of HbhA, other molecules serve as C3-binding molecules on theM. tuberculosissurface. Taken together, these data indicate that HbhA is important in the infectivity ofM. tuberculosis, but its ability to bind C3 is not required for mycobacterial adherence to macrophage-like cells. Using the ΔhbhAmutant strain, a secondM. tuberculosisC3-binding protein similar in size to HbhA was identified as HupB, but the role of HupB as a C3-binding protein in intact organisms remains to be determined. |
| Databáze: | OpenAIRE |
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