title: A Unique Set of the Burkholderia Collagen-Like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection.
abstract: Burkholderia pseudomallei and Burkholderia mallei, classified as category B priority pathogens, are significant human and animal pathogens that are highly infectious and broad-spectrum antibiotic resistant. Currently, the pathogenicity mechanisms utilized by Burkholderia are not fully understood, and correct diagnosis of B. pseudomallei and B. mallei infection remains a challenge due to limited detection methods. Here, we provide a comprehensive analysis of a set of 13 novel Burkholderia collagen-like proteins (Bucl) that were identified among B. pseudomallei and B. mallei select agents. We infer that several Bucl proteins participate in pathogenesis based on their noncollagenous domains that are associated with the components of a type III secretion apparatus and membrane transport systems. Homology modeling of the outer membrane efflux domain of Bucl8 points to a role in multi-drug resistance. We determined that bucl genes are widespread in B. pseudomallei and B. mallei; Fischer's exact test and Cramer's V2 values indicate that the majority of bucl genes are highly associated with these pathogenic species versus nonpathogenic B. thailandensis. We designed a bucl-based quantitative PCR assay which was able to detect B. pseudomallei infection in a mouse with a detection limit of 50 CFU. Finally, chromosomal mapping and phylogenetic analysis of bucl loci revealed considerable genomic plasticity and adaptation of Burkholderia spp. to host and environmental niches. In this study, we identified a large set of phylogenetically unrelated bucl genes commonly found in Burkholderia select agents, encoding predicted pathogenicity factors, detection targets, and vaccine candidates.
authors.affiliation: Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Bachert
authors.affiliation: Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Soo J
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Department of Biology, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Snyder
authors.affiliation: Department of Biology, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Rita V M
authors.initials: RV
authors.lastname: Rio
authors.affiliation: Department of Chemistry, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Brandon C
authors.initials: BC
authors.lastname: Durney
authors.affiliation: Department of Chemistry, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Holland
authors.affiliation: Bacteriology Division, The United States Army of Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Kei
authors.initials: K
authors.lastname: Amemiya
authors.affiliation: Bacteriology Division, The United States Army of Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Welkos
authors.affiliation: Bacteriology Division, The United States Army of Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Bozue
authors.affiliation: Bacteriology Division, The United States Army of Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Cote
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council, Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
authors.affiliation: Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Lukomski
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019117:Burkholderia / Q000145:classification / Q000472:pathogenicity / Q000502:physiology*; D019121:Burkholderia Infections / Q000382:microbiology*; D019295:Computational Biology; D019143:Evolution, Molecular; D017353:Gene Deletion; D015321:Gene Rearrangement; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D012641:Selection, Genetic; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins