About the Database of Burkholderia Secretion Systems

The Database of Burkholderia Secretion Systems 2.0 (DBSecSys 2.0) contains a curated set of 204 Burkholderia mallei (strain ATCC 23344) and 281 Burkholderia pseudomallei (strain K96243) proteins, which are either associated with 5 secretion systems or are known to be secreted but their secretion system type is undetermined. For these proteins, 170 B. mallei proteins are associated with 12 inferred pathogen mechanisms of action and 179 B. pseudomallei proteins are associated with 13 inferred pathogen mechanisms of action. Additionally, DBSecSys 2.0 contains more than 4,500 host-pathogen interactions between human/murine proteins and bacterial proteins associated with secretion systems. Finally, DBSecSys 2.0 contains a curated list of putative virulence factors (associated with secretion systems) screened for virulence attenuation (by genetic ablation) in vivo for at least one of the two bacteria. Summary of the database content and definitions of mechanisms of action used in the database are shown in Table 1 and Table 2, respectively.

Table 1. Summary of the content of DBSecSys 2.0

Number of B. mallei:
Proteins 204
Associated secretion systems 5
Virulence factors 52
Virulence attenuation experiments 82
Inferred mechanisms of action 12
Number of B. pseudomallei:
Proteins 281
Associated secretion systems 5
Virulence factors 61
Virulence attenuation experiments 98
Inferred mechanisms of action 13
Number of host-pathogen protein-protein interactions:
Human-B. mallei (experimental) 569
Murine-B. mallei (experimental) 788
Human-B. mallei (computational) 608
Murine-B. mallei (computational) 435
Human-B. pseudomallei (experimental) 4
Human-B. pseudomallei (computational) 1,117
Murine-B. pseudomallei (computational) 1,165

Table 2. Description of pathogenic mechanisms of action included in DBSecSys 2.0

Name Pathogens use this mechanism to:
Actin cytoskeleton rearrangement Subvert the host cell cytoskeleton to promote attachment to the host cell surface, internalization in the host cell, and prevent uptake by phagocytic cells.
Actin-based motility Bind to host actin, triggering actin polymerization on the pathogens’ surface and producing a mechanical force that propels them through the host cell and facilitates cell-to-cell spread.
Adhesion Attach to the host cell surface, promoting bacterial internalization in the host cell.
Apoptosis Exert control on the processes that regulate apoptosis in the host.
Cytotoxicity* Secrete toxins into the host cell.
Interference with signaling Interfere with the host signaling cascade, promoting their internalization in the host cell and intracellular survival.
Interference with the immune response Downregulate host inflammatory responses, promoting their internalization in the host cell and intracellular survival.
Intracellular survival* Evade the host immune response and multiply in the host cell.
Invasion Promote their ability to invade the host cell.
Multinucleated giant cell formation Induce host cell fusion and multinucleated giant cell formation.
Phagosomal escape and evasion of autophagy Ensure bacterial escape from endocytic vesicles as well as to evade autophagosomes, ensuring the pathogens’ intracellular survival and cell-to-cell spread.
Regulation* Control secretion system activation and related mechanisms of pathogenicity.
Ubiquitination - deubiquitination Interfere with host ubiquitination processes to attenuate the host immune response, to prevent their degradation, and to ensure their destruction when no longer required for establishing the infection.

*Mechanisms of action added in the updated database

The genomic localization of 3 of the 5 secretion systems in B. mallei and B. pseudomallei, type 1, type 2, and type 5 secretion systems, are not clearly delineated on the two chromosomes, whereas the type 3 and type 6 secretion systems are encoded on multiple clusters of genes. Some proteins assigned to secretion systems are not localized within known secretion systems clusters, whereas other proteins are known to be secreted but their secretion mechanisms are undetermined. Table 3 and Table 4 summarize the number of secretion system proteins in DBSecSys 2.0.

Table 3. Secretion systems consisting of a single protein cluster and/or individual proteins

Secretion system type Description of secretion systems Number of proteins
B. pseudomallei K96243 B. mallei ATCC 23344
1 Consists of three protein subunits: the ATP-binding cassette (ABC) transporters, membrane fusion proteins, and outer membrane protein. Transports various proteins, e.g., RTX toxins and the lipases, as well as non-proteinaceous substrates.
9
6
2 Represents a Sec/Tat-dependent system. Sometimes used by Gram-negative bacteria type IV pili for their biogenesis.
51
40
5 Also known as the autotransporter system and is divided into three types: 1) the archetypal bacterial proteins exported into the periplasm via the Sec system; 2) trimeric proteins with a single beta barrel domain; and 3) pairs of proteins in which one partner carries the beta barrel domain and the other partner is the secreted protein.
13
10
Undetermined Proteins are secreted, but the secretion mechanism has not been determined.
11
8

Table 4. Secretion systems consisting of multiple protein clusters and/or individual proteins

Secretion system type Description of secretion systems B. pseudomallei K96243 B. mallei ATCC 23344
Cluster number Number of proteins in each cluster Cluster number Number of proteins in each cluster
3 Consists of a double-membrane embedded protein delivery machine that transfers bacterial effector proteins to the cytoplasm or the plasma membrane of target eukaryotic cells. 1
19
1
N/A
2
19
2
15
Adjacent to Cluster 2
4
Adjacent to Cluster 2
4
3
33
3
35
Adjacent to Cluster 3
4
Adjacent to Cluster 3
3
Outside of Annotated Clusters
8
Outside of Annotated Clusters
8
6 Consists of a cell envelope spanning machine that translocates bacterial effector proteins into eukaryotic and prokaryotic cells and has a pivotal role in pathogenesis and bacterial competition. 1
19
1
19
2
19
2
16
3
16
3
16
4
19
4
16
5
20
5
N/A
6
15
6
5
Outside of Annotated Clusters
2
Outside of Annotated Clusters
2

Related resources

Links to the several databases of secretion systems for multiple pathogens that provide general information about secretion system proteins are provided below. They can be used as complementary resources to more specific information about B. mallei and B. pseudomallei protein functions, pathogenic mechanisms of action, experimental results, and host-interacting partners contained in DBSecSys.

Contact

For more information about the current database, archives of the previous version, curation issues, or data submission, please contact dbsecsys@bhsai.org