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From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins
Published on: July 4, 2016
A family of variably expressed outer-membrane proteins (Vomp) mediates adhesion and autoaggregation in Bartonella
Peng Zhang1, Bruno B Chomel, Maureen K Schau
1Division of Infectious Diseases, Department of Medicine, University of California-San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0654.
Abstract:
Bartonella species are fastidious, Gram-negative human pathogens that can persist in the host bloodstream for years and bind to and invade several types of host cells. For many pathogens, adhesion to host cells and extracellular matrix (ECM) components is a critical virulence determinant. Bacteria often vary expression of surface adhesins by phase or antigenic variation to subvert the host immune response and permit adaptive interaction with different host structures. We developed a macaque animal model for Bartonella quintana infection to detect changes in bacterial outer-membrane proteins (OMP) during prolonged bloodstream infection. We identified a gene family encoding four highly conserved, 100-kDa, variably expressed OMP (Vomp), two of which function as adhesins. The variable expression of Vomp family members appears to be mediated by deletion of one or more vomp genes during chronic bloodstream infection. vomp deletion was observed also in isolates from humans with chronic B. quintana infection. The Vomp are closely related to the afimbrial adhesin, YadA, a virulence factor of Yersinia enterocolitica. The surface-expressed Vomp contain conserved structural features of YadA, including collagen-binding motifs. We demonstrate that the B. quintana Vomp are multifunctional OMP involved in binding to collagen and autoaggregation: VompC confers the ability to bind collagen IV, and VompA is necessary and sufficient for autoaggregation. The B. quintana Vomp are members of the newly recognized family of YadA-like trimeric autotransporters; the Vomp constitute a multigene family, they are variably expressed, and different virulence properties are attributable to individual Vomp family members.
Insights
Bartonella quintana outer-membrane proteins (Vomp) are variably expressed during chronic infection, with some acting as adhesins. Gene deletion mechanisms drive this variation, impacting bacterial virulence.
Area of Science:
- Microbiology
- Pathogen Biology
- Immunology
Background:
- Bartonella species are Gram-negative bacteria causing persistent human infections.
- Bacterial adhesion to host cells and extracellular matrix (ECM) is crucial for virulence.
- Pathogens often modulate surface protein expression to evade immune responses.
Purpose of the Study:
- To investigate changes in Bartonella quintana outer-membrane proteins (OMP) during prolonged bloodstream infection using a macaque model.
- To identify and characterize novel adhesins involved in Bartonella pathogenesis.
Main Methods:
- Development of a macaque animal model for Bartonella quintana infection.
- Analysis of bacterial outer-membrane proteins (OMP) from chronic infection isolates.
- Identification of a gene family encoding variably expressed outer-membrane proteins (Vomp).
Main Results:
- Identified a family of four conserved, 100-kDa, variably expressed OMP (Vomp) in B. quintana.
- Demonstrated that two Vomp proteins function as adhesins, binding to collagen and mediating autoaggregation.
- Observed variable Vomp expression mediated by gene deletion in both animal models and human isolates.
Conclusions:
- Bartonella quintana Vomp are multifunctional adhesins belonging to the YadA-like trimeric autotransporter family.
- Variable expression of Vomp through gene deletion is a key mechanism for adapting to host environments during chronic infection.
- Individual Vomp family members contribute distinct virulence properties, such as collagen binding and autoaggregation.
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