Resistance of<i>Mycoplasma pulmonis</i>to Complement Lysis Is Dependent on the Number of Vsa Tandem Repeats: Shield Hypothesis

Simmons, Warren L.; Denison, Amy M.; Dybvig, Kevin

doi:10.1128/iai.72.12.6846-6851.2004

Cited by 34 publications

(58 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was possible that analysis by immunoblotting would have revealed that, over time, isolates gain an even larger number of tandem repeats to avoid the complement system. However, because the initial inoculum produced a Vsa protein with a large number of tandem repeats, the mycoplasma was already resistant to complement lysis (26), and no selection pressure was evidently present to promote further expansion of the tandem repeats. If the initial inoculum had been a mycoplasma population producing a Vsa protein with few tandem repeats, it is hypothesized that size variation would have occurred over time to generate mycoplasmas with a large number of tandem repeats to acquire resistance to complement killing or the growth-inhibitory effects of specific antibody (6).…”

Section: Resultsmentioning

confidence: 99%

“…Vsa size variation is thought to occur by slipped-strand mispairing within the tandem repeats of the vsa gene during DNA replication and has been shown to have a role in modulating the susceptibility of the cell to complement lysis. Isolates with a large number of tandem repeats are resistant to complement-mediated killing, whereas isolates with few tandem repeats are susceptible (26,27).Previous work in our laboratory noted that in rats infected intranasally with a strain of M. pulmonis that produced VsaA, selection pressures caused a shift of the mycoplasma population toward cells that produced a Vsa protein other than VsaA. Switching of the Vsa protein that was produced occurred in the lower respiratory tract but not in the nose (12).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Avoidance of the Host Immune System through Phase Variation in Mycoplasma pulmonis

Denison¹,

Clapper²,

Dybvig

2005

Infect Immun

Self Cite

View full text Add to dashboard Cite

Phase-variable lipoproteins are commonly found in Mycoplasma species. Mycoplasma pulmonis contains a family of extensively studied phase-and size-variable lipoproteins encoded by the vsa locus. The Vsa surface proteins vary at a high frequency, the in vivo significance of which has yet to be determined. We investigated the role of Vsa phase variation in respect to tissue tropism and avoidance of the immune system in the mouse host. Mycoplasmas were cultured 3, 14, and 21 days postinoculation from the nose, lung, trachea, liver, and spleen of experimentally infected C57BL/6 (wild-type), C57BL/6-RAG-1 ؊/؊ (RAG ؊/؊ ), and C57BL/6-inducible nitric oxide synthase (iNOS) ؊/؊ (iNOS ؊/؊ ) mice. In wild-type and iNOS ؊/؊ mice, a large number of Vsa variants were seen by 21 days postinoculation. In contrast, little Vsa variation occurred in all tissues of RAG ؊/؊ mice. Analysis of isolates from 14 days postinoculation revealed less variation of the Vsa proteins in iNOS ؊/؊ mice than in the wild type. Western blot analysis of isolates from each strain of mouse demonstrated that Vsa phase variation occurred independently of size variation, indicating no obvious selection pressure for size variants. Additionally, these experiments provided no evidence that mycoplasmas producing particular Vsa proteins adhered only to specific tissues. The data strongly indicate that Vsa phase variation is a mechanism for avoidance of the immune system with no obvious contribution to tissue tropism.Phase variation is a common mechanism thought to aid in microbial survival by allowing for the presence of diverse subpopulations that can quickly respond to changing environmental conditions (9, 13). Among the better-studied models of phase variation is the pilin protein of Neisseria gonorrhoeae, where phase variation affects competence for DNA transformation (24), adherence to epithelial cells (17, 23), and avoidance of the host immune system (2). Mycoplasmas possess an abundance of phase-variable proteins, especially surface-exposed lipoproteins (20,30,31). The in vivo significance of phase-variable lipoproteins from Mycoplasma species has not yet been established but may function in gene transfer, tissue tropism, or avoidance of the host immune system like that of pilin variation of N. gonorrhoeae.Mycoplasma pulmonis, the causative agent of murine respiratory mycoplasmosis, produces a family of phase-and sizevariable surface-bound lipoproteins encoded by the vsa (for variable surface antigen) genes. The amino terminus of the Vsa proteins is composed of a conserved domain of 242 amino acids, and the carboxy terminus is a variable domain usually consisting of numerous tandem repeats (25). Each cell will express the vsa gene that is associated with the single vsa expression site. This site contains the vsa promoter and the first 714 nucleotides of the coding region. Different vsa genes can become expressed by site-specific DNA inversions, catalyzed by the HvsR recombinase (29) at a 34-bp site termed the vsa recombination site (vrs box) (1). The CT...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Avoidance of the Host Immune System through Phase Variation in Mycoplasma pulmonis

Denison¹,

Clapper²,

Dybvig

2005

Infect Immun

Self Cite

View full text Add to dashboard Cite

show abstract

“…There are no known two-component regulatory systems or other recognizable global regulators in most species of mycoplasmas, including Mycoplasma pulmonis. The lack of such regulators can be attributed to the survival of the mycoplasmas in only one environmental niche: the animal host.The variable surface antigen (Vsa) proteins of the murine respiratory pathogen M. pulmonis are associated with virulence (34) and mediate the susceptibility of the mycoplasma cells to complement (26,27). A Vsa protein contains a conserved N-terminal region attached to one of several C-terminal tandem repeat regions (3, 28).…”

mentioning

confidence: 99%

“…Independent of the particular vsa gene that occupies the vsa expression site, mycoplasmas that produce a long form of the Vsa protein of about 40 tandem repeats do not adhere to polystyrene or erythrocytes. These mycoplasmas are resistant to killing by complement (26,27). Mycoplasmas that produce a short Vsa protein with only a few tandem repeats (e.g., five repeats or less) adhere to polystyrene, adsorb erythrocytes, and are efficiently killed by complement.…”

mentioning

confidence: 99%

A Stochastic Mechanism for Biofilm Formation by Mycoplasma pulmonis

Simmons¹,

Bolland

Daubenspeck

et al. 2007

J Bacteriol

Self Cite

View full text Add to dashboard Cite

Bacterial biofilms are communities of bacteria that are enclosed in an extracellular matrix. Within a biofilm the bacteria are protected from antimicrobials, environmental stresses, and immune responses from the host. Biofilms are often believed to have a highly developed organization that is derived from differential regulation of the genes that direct the synthesis of the extracellular matrix and the attachment to surfaces. The mycoplasmas have the smallest of the prokaryotic genomes and apparently lack complex gene-regulatory systems. We examined biofilm formation by Mycoplasma pulmonis and found it to be dependent on the length of the tandem repeat region of the variable surface antigen (Vsa) protein. Mycoplasmas that produced a short Vsa protein with few tandem repeats formed biofilms that attached to polystyrene and glass. Mycoplasmas that produced a long Vsa protein with many tandem repeats formed microcolonies that floated freely in the medium. The biofilms and the microcolonies contained an extracellular matrix which contained Vsa protein, lipid, DNA, and saccharide. As variation in the number of Vsa tandem repeats occurs by slipped-strand mispairing, the ability of the mycoplasmas to form a biofilm switches stochastically.Biofilm formation can enhance the resistance of pathogens to antimicrobial agents (6) and immune surveillance (36). This has been attributed in part to the encasement within an extracellular matrix of the biofilm that isolates and protects the bacteria from the host immune response. The extracellular matrix of a biofilm is complex and usually contains lipid, protein, DNA, and exopolysaccharide (1, 2, 4, 38). Most studies have focused on the complexity of the molecular systems involved in the formation of the matrix constituents. The formation of biofilms by some bacteria is dependent on two-component and quorum-sensing systems that regulate macromolecules necessary for attachment and matrix synthesis (24). A recent trend is to describe biofilm formation in the context of a multicellular structure that develops as a result of programmed gene expression (7,21).Few studies address the formation of biofilms from the viewpoint of simplicity. The recent finding that mycoplasmas can form biofilms (19) provides us with a model in which microorganisms using minimally regulated genetic systems, or perhaps stochastically modulated genetic systems, can form biofilms. The mycoplasmas are the smallest and simplest of self-replicating cells (11,22). Although some mycoplasmas can produce complex structures such as an attachment organelle, their genomes encode only a few hundred proteins. There are no known two-component regulatory systems or other recognizable global regulators in most species of mycoplasmas, including Mycoplasma pulmonis. The lack of such regulators can be attributed to the survival of the mycoplasmas in only one environmental niche: the animal host.The variable surface antigen (Vsa) proteins of the murine respiratory pathogen M. pulmonis are associated with virulence (34) and media...

show abstract