Association and Evidence for Linked Recognition of Type IV Secretion System Proteins VirB9-1, VirB9-2, and VirB10 in Anaplasma marginale

Morse, Kaitlyn; Norimine, Junzo; Palmer, Guy H.; Sutten, Eric L.; Baszler, Timothy V.; Brown, Wendy C.

doi:10.1128/iai.05798-11

Cited by 22 publications

(49 citation statements)

References 63 publications

(100 reference statements)

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“…CD4 ϩ T cells primed during recognition of tetanus toxoid antigen can then provide help to B cells, which produce antibody targeting the capsular polysaccharide. In the case of A. marginale, linkage between molecules has been shown to enhance antibody production and may also increase the repertoire of antibodies that target the type IV secretion system proteins (26,27).…”

Section: Discussionmentioning

confidence: 99%

Linkage between Anaplasma marginale Outer Membrane Proteins Enhances Immunogenicity but Is Not Required for Protection from Challenge

Noh¹,

Turse²,

Brown³

et al. 2013

Clin. Vaccine Immunol.

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The prevention of bacterial infections via immunization presents particular challenges. While outer membrane extracts are often protective, they are difficult and expensive to isolate and standardize and thus are often impractical for development and implementation in vaccination programs. In contrast, individual proteins, which are easily adapted for use in subunit vaccines, tend to be poorly protective. Consequently, identification of the specific characteristics of outer membrane-based immunogens, in terms of the antigen contents and contexts that are required for protective immunity, represents a major gap in the knowledge needed for bacterial vaccine development. Using as a model Anaplasma marginale, a persistent tick-borne bacterial pathogen of cattle, we tested two sets of immunogens to determine whether membrane context affected immunogenicity and the capacity to induce protection. The first immunogen was composed of a complex of outer membrane proteins linked by covalent bonds and known to be protective. The second immunogen was derived directly from the first one, but the proteins were individualized rather than linked. The antibody response induced by the linked immunogen was much greater than that induced by the unlinked immunogen. However, both immunogens induced protective immunity and an anamnestic response. These findings suggest that individual proteins or combinations of proteins can be successfully tested for the ability to induce protective immunity with less regard for overall membrane context. Once protective antigens are identified, immunogenicity could be enhanced by cross-linking to allow a reduced immunogen dose or fewer booster vaccinations.

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Section: Discussionmentioning

confidence: 99%

Linkage between Anaplasma marginale Outer Membrane Proteins Enhances Immunogenicity but Is Not Required for Protection from Challenge

Noh¹,

Turse²,

Brown³

et al. 2013

Clin. Vaccine Immunol.

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“…4A and B). These cell lines did respond to A. marginale OM and responded variably to type 4 secretion system proteins VirB9-1 (CTP) and VirB9-2 (VirBa) expressed by IVTT and bound to protein G beads, as we have shown previously (53,65,86).…”

Section: Identification Of S Aureus Antigens That Induced Significanmentioning

confidence: 89%

“…Furthermore, only two cattle shared one MHC class II haplotype; animals 30864 (12/16) and 30904 (11/16) have the DRB3 RFLP haplotype 16. Thus, the finding that these three antigens stimulate recall responses from two to four animals with completely different haplotypes and the fact that these haplotypes are common among North American Holstein cattle (65,77) suggest that these are good candidates for inclusion in a multiantigen vaccine that would be broadly protective in Holstein cattle. Two of these antigens are putative lipoproteins, and one is the alkaline shock protein.…”

Section: Identification Of S Aureus Antigens That Induced Significanmentioning

confidence: 99%

“…During the course of this study, all animals maintained recall T cell responses, which enabled the development of S. aureus-specific short-term T cell lines. Two calves expressing different MHC-II haplotypes, 16/22 (animal 35287) and 8/23 (animal 583), and immunized with A. marginale outer membranes (OM) as described previously (55,65) were used as a source of peripheral blood mononuclear cells (PBMC) for lymphocyte proliferation assays with S. aureus antigens as negative controls. Animals used in this study were in compliance with the Washington State University Institutional Animal Care and Use Committee.…”

Section: Methodsmentioning

confidence: 99%

“…For an additional negative control to rule out nonspecific proliferation to the IVTT-expressed proteins, 2-week T cell lines were derived from two A. marginale outer membrane (OM)-vaccinated cattle as described previously (65). PBMC were cultured for 1 week with 1 g/ml A. marginale OM and rested for 1 week and then tested as described above in proliferation assays.…”

Section: Methodsmentioning

confidence: 99%

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CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

Lawrence¹,

Rokbi²,

Arnaud-Barbe³

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTStaphylococcus aureusis a commensal bacterium associated with the skin and mucosal surfaces of humans and animals that can also cause chronic infection. The emergence of antibiotic-resistant strains such as methicillin-resistantS. aureus(MRSA) and strains causing chronic intramammary infections (IMI) in cows results in severe human and livestock infections. Conventional approaches to vaccine development have yielded only a few noneffective vaccines against MRSA or IMI strains, so there is a need for improved vaccine development. CD4 T lymphocytes are required for promoting gamma interferon (IFN-γ) mediated immunoglobulin isotype switching in B lymphocytes to produce high-affinity IgG antibodies and IFN-γ-mediated phagocyte activation for an effective resolution of bacterial infection. However, the lack of known CD4 T cell antigens fromS. aureushas made it difficult to design effective vaccines. The goal of this study was to identifyS. aureusproteins recognized by immune CD4 T cells. Using a reverse genetics approach, 43 antigens were selected from theS. aureusNewman strain. These included lipoproteins, proteases, transcription regulators, an alkaline shock protein, conserved-domain proteins, hemolysins, fibrinogen-binding protein, staphylokinase, exotoxin, enterotoxin, sortase, and protein A. Screening of expressed proteins for recall T cell responses in outbred, immune calves identified 13 proteins that share over 80% sequence identity among MRSA or IMI strains. These may be useful for inclusion in a broadly protective multiantigen vaccine against MRSA or IMI.

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Role and Function of the Type IV Secretion System in Anaplasma and Ehrlichia Species

Rikihisa

2017

Current Topics in Microbiology and Immunology

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The obligatory intracellular pathogens Anaplasma phagocytophilum and Ehrlichia chaffeensis proliferate within membrane-bound vacuoles of human leukocytes and cause potentially fatal emerging infectious diseases. Despite the reductive genome evolution in this group of bacteria, genes encoding the type IV secretion system (T4SS), which is homologous to the VirB/VirD4 system of the plant pathogen Agrobacterium tumefaciens, have been expanded and are highly expressed in A. phagocytophilum and E. chaffeensis in human cells. Of six T4SS effector proteins identified in them, roles and functions have been described so far only for ankyrin repeat domain-containing protein A (AnkA), Anaplasma translocated substrate 1 (Ats-1), and Ehrlichia translocated factor 1 (Etf-1, ECH0825). These effectors are abundantly produced and secreted into the host cytoplasm during infection, but not toxic to host cells. They contain eukaryotic protein motifs or organelle localization signals and have distinct subcellular localization, target to specific host cell molecules to promote infection. Ats-1 and Etf-1 are orthologous proteins, subvert two important innate immune mechanisms against intracellular infection, cellular apoptosis and autophagy, and manipulate autophagy to gain nutrients from host cells. Although Ats-1 and Etf-1 have similar functions and roles in obligatory intracellular infection, they are specifically adapted to the distinct membrane-bound intracellular niche of A. phagocytophilum and E. chaffeensis, respectively. Ectopic expression of these effectors enhances respective bacterial infection, whereas intracellular delivery of antibodies against these effectors or targeted knockdown of the effector with antisense peptide nucleic acid significantly impairs bacterial infection. Thus, both T4SSs have evolved as important survival and nutritional virulence mechanism in these obligatory intracellular bacteria. Future studies on the functions of Anaplasma and Ehrlichia T4SS effector molecules and signaling pathways will undoubtedly advance our understanding of the complex interplay between obligatory intracellular pathogens and their hosts. Such data can be applied toward the treatment and control of anaplasmosis and ehrlichiosis.

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Association and Evidence for Linked Recognition of Type IV Secretion System Proteins VirB9-1, VirB9-2, and VirB10 in Anaplasma marginale

Cited by 22 publications

References 63 publications

Linkage between Anaplasma marginale Outer Membrane Proteins Enhances Immunogenicity but Is Not Required for Protection from Challenge

Linkage between Anaplasma marginale Outer Membrane Proteins Enhances Immunogenicity but Is Not Required for Protection from Challenge

CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

Role and Function of the Type IV Secretion System in Anaplasma and Ehrlichia Species

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