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Published on: October 16, 2018
The Vsa proteins modulate susceptibility of Mycoplasma pulmonis to complement killing, hemadsorption, and adherence
Warren L Simmons1, Kevin Dybvig
1Department of Genetics, University of Alabama at Birmingham, 720 South 20th Street, Kaul Room 720, Birmingham, AL 35294, USA. wsimmons@uab.edu
Abstract:
The variable surface antigens (Vsa) of the murine respiratory pathogen Mycoplasma pulmonis are associated with the virulence of the microorganism in the lung. In strain UAB CT, the antigens consist of an N-terminal region that is combined with one of seven different C-terminal variable regions comprised of tandem repeats. M. pulmonis producing a VsaA protein with about 40 tandem repeats (R40) does not adhere to red blood cells or polystyrene. Strains that produce VsaH contain a short C-terminal region that lacks tandem repeats and adhere to red blood cells and plastic. We isolated and analyzed M. pulmonis strain CT variants (CT182 and derivatives) that produced a VsaA protein with only three tandem repeats (R3). These variants adhered to plastic and red blood cells similarly to the VsaH-producing strain. When the R3-producing CT182 strain or the VsaH-producing strains were incubated with normal guinea pig serum, they were efficiently killed. Killing was abolished when the serum was heat inactivated. In contrast, the M. pulmonis strains that produced VsaA R40 were highly resistant to complement killing. CT182R3 variants that survived the complement killing reactions all produced the R40 form of VsaA and were resistant to complement killing. VsaA R40 is the first mycoplasmal protein shown to be associated with resistance to complement. As both VsaH and VsaA can mediate adherence to plastic, cytadherence, and susceptibility to complement, we propose that Vsa modulates these phenotypes by nonspecific interactions.
Insights
Mycoplasma pulmonis variable surface antigens (Vsa) influence virulence. Shorter VsaA variants (R3) increase adherence and complement susceptibility, while longer VsaA (R40) confers resistance, suggesting Vsa modulates phenotypes via interactions.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Mycoplasma pulmonis, a murine respiratory pathogen, possesses variable surface antigens (Vsa) linked to virulence.
- Vsa proteins in strain UAB CT comprise a common N-terminal region and variable C-terminal regions with tandem repeats.
- Different Vsa variants exhibit distinct adherence properties and susceptibility to host immune mechanisms.
Purpose of the Study:
- To investigate the role of VsaA tandem repeat number in Mycoplasma pulmonis adherence and complement resistance.
- To characterize M. pulmonis variants with altered VsaA structures and their interactions with host factors.
Main Methods:
- Isolation and analysis of Mycoplasma pulmonis strain CT variants producing VsaA with varying tandem repeats (R3 vs. R40).
- Assessment of bacterial adherence to red blood cells and polystyrene.
- Evaluation of bacterial susceptibility to complement-mediated killing using normal and heat-inactivated guinea pig serum.
Main Results:
- Mycoplasma pulmonis variants producing VsaA with three tandem repeats (R3) showed increased adherence to plastic and red blood cells.
- R3-producing strains and VsaH-producing strains were susceptible to complement-mediated killing, which was abolished by heat inactivation of serum.
- Strains producing VsaA with approximately 40 tandem repeats (R40) exhibited high resistance to complement killing.
- CT182R3 variants surviving complement exposure upregulated VsaA R40 production, conferring resistance.
Conclusions:
- VsaA R40 is the first identified mycoplasmal protein associated with resistance to complement-mediated killing.
- Both VsaH and VsaA mediate adherence and influence complement susceptibility.
- The study proposes that Vsa modulates cytadherence and complement sensitivity through non-specific interactions, impacting Mycoplasma pulmonis virulence.
