{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T22:44:08Z","timestamp":1768776248468,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation (FCT)","doi-asserted-by":"publisher","award":["UID\/BIO\/04565\/2020"],"award-info":[{"award-number":["UID\/BIO\/04565\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Burkholderia cenocepacia is a multi-drug-resistant lung pathogen. This species synthesizes various virulence factors, among which cell-surface components (adhesins) are critical for establishing the contact with host cells. This work in the first part focuses on the current knowledge about the adhesion molecules described in this species. In the second part, through in silico approaches, we perform a comprehensive analysis of a group of unique bacterial proteins possessing collagen-like domains (CLDs) that are strikingly overrepresented in the Burkholderia species, representing a new putative class of adhesins. We identified 75 CLD-containing proteins in Burkholderia cepacia complex (Bcc) members (Bcc-CLPs). The phylogenetic analysis of Bcc-CLPs revealed the evolution of the core domain denominated \u201cBacterial collagen-like, middle region\u201d. Our analysis remarkably shows that these proteins are formed by extensive sets of compositionally biased residues located within intrinsically disordered regions (IDR). Here, we discuss how IDR functions may increase their efficiency as adhesion factors. Finally, we provided an analysis of a set of five homologs identified in B. cenocepacia J2315. Thus, we propose the existence in Bcc of a new type of adhesion factors distinct from the described collagen-like proteins (CLPs) found in Gram-positive bacteria.<\/jats:p>","DOI":"10.3390\/microorganisms11051118","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T04:27:02Z","timestamp":1682396822000},"page":"1118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In-Silico Analysis Highlights the Existence in Members of Burkholderia cepacia Complex of a New Class of Adhesins Possessing Collagen-like Domains"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4862-777X","authenticated-orcid":false,"given":"Ricardo","family":"Estevens","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-3579","authenticated-orcid":false,"given":"Dalila","family":"Mil-Homens","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"},{"name":"Institute for Bioengineering and Biosciences (iBB), Instituto Superior T\u00e9cnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"},{"name":"Institute for Health and Bioeconomic (i4HB), Instituto Superior T\u00e9cnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-5787","authenticated-orcid":false,"given":"Arsenio M.","family":"Fialho","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"},{"name":"Institute for Bioengineering and Biosciences (iBB), Instituto Superior T\u00e9cnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"},{"name":"Institute for Health and Bioeconomic (i4HB), Instituto Superior T\u00e9cnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nrmicro1085","article-title":"The Multifarious, Multireplicon Burkholderia Cepacia Complex","volume":"3","author":"Mahenthiralingam","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1128\/JCM.39.10.3427-3436.2001","article-title":"Taxonomy and Identification of the Burkholderia Cepacia Complex","volume":"39","author":"Coenye","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1574-6968.1996.tb08517.x","article-title":"Genomic Complexity and Plasticity of Burkholderia cepacia","volume":"144","author":"Lessie","year":"1996","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/S0022-3476(86)80749-1","article-title":"Pseudomonas cepacia: Biology, Mechanisms of Virulence, Epidemiology","volume":"108","author":"Goldmann","year":"1986","journal-title":"J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0022-3476(84)80993-2","article-title":"Pseudomonas cepacia Infection in Cystic Fibrosis: An Emerging Problem","volume":"104","author":"Isles","year":"1984","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0378-1097(03)00724-9","article-title":"Evidence of Transmission of Burkholderia cepacia, Burkholderia multivorans and Burkholderia dolosa among Persons with Cystic Fibrosis","volume":"228","author":"Biddick","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/jmm.0.47788-0","article-title":"Burkholderia Cepacia Complex: Epithelial Cell-Pathogen Confrontations and Potential for Therapeutic Intervention","volume":"58","author":"McClean","year":"2009","journal-title":"J. Med. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00848-19","DOI":"10.1128\/mBio.00848-19","article-title":"Transcriptomic Analysis of Streptococcus Pyogenes Colonizing","volume":"10","author":"Cook","year":"2019","journal-title":"MBio"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Khater, F., Balestrino, D., Charbonnel, N., Dufayard, J.F., Brisse, S., and Forestier, C. (2015). In Silico Analysis of Usher Encoding Genes in Klebsiella Pneumoniae and Characterization of Their Role in Adhesion and Colonization. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116215"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1128\/MMBR.00039-06","article-title":"Listeria monocytogenes Surface Proteins: From Genome Predictions to Function","volume":"71","author":"Bierne","year":"2007","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.1038\/s41598-021-85222-5","article-title":"Burkholderia cenocepacia Transcriptome during the Early Contacts with Giant Plasma Membrane Vesicles Derived from Live Bronchial Epithelial Cells","volume":"11","author":"Pimenta","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-7553-2_1","article-title":"Surfaceome Analysis Protocol for the Identification of Novel Bordetella pertussis","volume":"Volume 1722","author":"Boheler","year":"2018","journal-title":"The Surfaceome"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1128\/IAI.01248-15","article-title":"Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia Cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection","volume":"84","author":"McClean","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_14","first-page":"217","article-title":"The Blot Rolling Assay","volume":"Volume 341","author":"Colgan","year":"2006","journal-title":"Methods in Molecular Biology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.3762\/bjnano.5.163","article-title":"Hydrophobic Interaction Governs Unspecific Adhesion of Staphylococci: A Single Cell Force Spectroscopy Study","volume":"5","author":"Thewes","year":"2014","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1016\/j.bpj.2013.03.046","article-title":"Single-Cell Force Spectroscopy of Probiotic Bacteria","volume":"104","author":"Beaussart","year":"2013","journal-title":"Biophys. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/j.1469-0691.2010.03237.x","article-title":"Burkholderia cenocepacia in Cystic Fibrosis: Epidemiology and Molecular Mechanisms of Virulence","volume":"16","author":"Drevinek","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5426","DOI":"10.1128\/IAI.73.9.5426-5437.2005","article-title":"Cable Pili and the 22-Kilodalton Adhesin Are Required for Burkholderia cenocepacia Binding to and Transmigration across the Squamous Epithelium","volume":"73","author":"Urban","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12691","DOI":"10.1111\/cmi.12691","article-title":"The Burkholderia cenocepacia Peptidoglycan-Associated Lipoprotein Is Involved in Epithelial Cell Attachment and Elicitation of Inflammation","volume":"19","author":"Dennehy","year":"2017","journal-title":"Cell. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1099\/mic.0.032623-0","article-title":"Genome-Wide Analysis of DNA Repeats in Burkholderia cenocepacia J2315 Identifies a Novel Adhesin-like Gene Unique to Epidemic-Associated Strains of the ET-12 Lineage","volume":"156","author":"Rocha","year":"2010","journal-title":"Microbiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1099\/mic.0.26176-0","article-title":"Identification and Molecular Analysis of Cable Pilus Biosynthesis Genes in Burkholderia cepacia","volume":"149","author":"Sajjan","year":"2003","journal-title":"Microbiology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shinoy, M., Dennehy, R., Coleman, L., Carberry, S., Schaffer, K., Callaghan, M., Doyle, S., and McClean, S. (2013). Immunoproteomic Analysis of Proteins Expressed by Two Related Pathogens, Burkholderia multivorans and Burkholderia cenocepacia, during Human Infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080796"},{"key":"ref_23","first-page":"15","article-title":"Burkholderia cenocepacia Differential Gene Expression during Host-Pathogen Interactions and Adaptation to the Host Environment","volume":"1","author":"Sokol","year":"2011","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.tim.2006.04.005","article-title":"Trimeric Autotransporter Adhesins: Variable Structure, Common Function","volume":"14","author":"Linke","year":"2006","journal-title":"Trends Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1128\/JB.01230-08","article-title":"The Genome of Burkholderia cenocepacia J2315, an Epidemic Pathogen of Cystic Fibrosis Patients","volume":"91","author":"Holden","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1128\/IAI.72.3.1537-1547.2004","article-title":"The Burkholderia Cepacia Epidemic Strain Marker Is Part of A Novel Genomic Island Encoding Both Virulence and Metabolism-Associated Genes in Burkholderia Cenocepacia","volume":"72","author":"Baldwin","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_27","first-page":"13","article-title":"Trimeric Autotransporter Adhesins in Members of the Burkholderia Cepacia Complex: A Multifunctional Family of Proteins Implicated in Virulence","volume":"1","author":"Fialho","year":"2011","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mil-Homens, D., and Fialho, A.M. (2012). A BCAM0223 Mutant of Burkholderia cenocepacia Is Deficient in Hemagglutination, Serum Resistance, Adhesion to Epithelial Cells and Virulence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041747"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1128\/JB.00061-14","article-title":"Characterization of BCAM0224, a Multifunctional Trimeric Autotransporter from the Human Pathogen Burkholderia cenocepacia","volume":"196","author":"Fernandes","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_30","first-page":"e12677","article-title":"Burkholderia cenocepacia K56-2 Trimeric Autotransporter Adhesin BcaA Binds TNFR1 and Contributes to Induce Airway Inflammation","volume":"19","author":"Pinto","year":"2017","journal-title":"Cell. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13340","DOI":"10.1111\/cmi.13340","article-title":"Burkholderia cenocepacia BCAM2418-Induced Antibody Inhibits Bacterial Adhesion, Confers Protection to Infection and Enables Identification of Host Glycans as Adhesin Targets","volume":"23","author":"Pimenta","year":"2021","journal-title":"Cell. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1093\/bioinformatics\/btn524","article-title":"The Burkholderia Genome Database: Facilitating Flexible Queries and Comparative Analyses","volume":"24","author":"Winsor","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/bioinformatics\/btq249","article-title":"PSORTb 3.0: Improved Protein Subcellular Localization Prediction with Refined Localization Subcategories and Predictive Capabilities for All Prokaryotes","volume":"26","author":"Yu","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/nar\/gkz303","article-title":"NGPhylogeny.Fr: New Generation Phylogenetic Services for Non-Specialists","volume":"47","author":"Lemoine","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Newman, A.M., and Cooper, J.B. (2007). XSTREAM: A Practical Algorithm for Identification and Architecture Modeling of Tandem Repeats in Protein Sequences. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-382"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4438","DOI":"10.1038\/s41467-021-24773-7","article-title":"FlDPnn: Accurate Intrinsic Disorder Prediction with Putative Propensities of Disorder Functions","volume":"12","author":"Hu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/nar\/gkx922","article-title":"20 Years of the SMART Protein Domain Annotation Resource","volume":"46","author":"Letunic","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively Expanding the Structural Coverage of Protein-Sequence Space with High-Accuracy Models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Qiu, Y., Zhai, C., Chen, L., Liu, X., and Yeo, J. (2021). Current Insights on the Diverse Structures and Functions in Bacterial Collagen-like Proteins. ACS Biomater. Sci. Eng.","DOI":"10.1021\/acsbiomaterials.1c00018"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Beth, A.B., Soo, J.C., Anna, K.S., Rita, V.M.R., Brandon, C.D., Lisa, A.H., Kei, A., Susan, L.W., Joel, A.B., and Christopher, K.C. (2015). A Unique Set of the Burkholderia Collagen-like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137578"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jsb.2014.01.003","article-title":"Bacterial Collagen-like Proteins That Form Triple-Helical Structures","volume":"186","author":"Yu","year":"2014","journal-title":"J. Struct. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/1574-6976.12036","article-title":"The Role of Variable DNA Tandem Repeats in Bacterial Adaptation","volume":"38","author":"Zhou","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e2768","DOI":"10.1002\/jmr.2768","article-title":"Sequence and Structural Analysis of Fibronectin-Binding Protein Reveals Importance of Multiple Intrinsic Disordered Tandem Repeats","volume":"32","author":"Saravanan","year":"2019","journal-title":"J. Mol. Recognit."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Nykyri, J., Mattinen, L., Niemi, O., Adhikari, S., K\u00f5iv, V., Somervuo, P., Fang, X., Auvinen, P., M\u00e4e, A., and Palva, E.T. (2013). Role and Regulation of the Flp\/Tad Pilus in the Virulence of Pectobacterium atrosepticum SCRI1043 and Pectobacterium wasabiae SCC3193. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073718"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"916247","DOI":"10.3389\/fcimb.2022.916247","article-title":"The Flp Type IV Pilus Operon of Mycobacterium tuberculosis is Expressed upon Interaction with Macrophages and Alveolar Epithelial Cells","volume":"12","author":"Alteri","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3389\/fmicb.2010.00131","article-title":"Host-Mediated Post-Translational Prenylation of Novel Dot\/ Icm-Translocated Effectors of Legionella pneumophila","volume":"1","author":"Price","year":"2010","journal-title":"Front. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"foaa018","DOI":"10.1093\/femsyr\/foaa018","article-title":"The Epithelial Adhesin 1 Tandem Repeat Region Mediates Protein Display through Multiple Mechanisms","volume":"20","author":"Raposo","year":"2020","journal-title":"FEMS Yeast Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"593356","DOI":"10.3389\/fmicb.2020.593356","article-title":"Streptococcal Serine-Rich Repeat Proteins in Colonization and Disease","volume":"11","author":"Chan","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6561","DOI":"10.1021\/cr400514h","article-title":"Introducing Protein Intrinsic Disorder","volume":"114","author":"Habchi","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00018-014-1661-9","article-title":"Exceptionally Abundant Exceptions: Comprehensive Characterization of Intrinsic Disorder in All Domains of Life","volume":"72","author":"Peng","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1021\/pr060049p","article-title":"Conservation of Intrinsic Disorder in Protein Domains and Families: II. Functions of Conserved Disorder","volume":"5","author":"Chen","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/07391102.2012.675145","article-title":"Orderly Order in Protein Intrinsic Disorder Distribution: Disorder in 3500 Proteomes from Viruses and the Three Domains of Life","volume":"30","author":"Xue","year":"2012","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mier, P., and Andrade-Navarro, M.A. (2021). The Conservation of Low Complexity Regions in Bacterial Proteins Depends on the Pathogenicity of the Strain and Subcellular Location of the Protein. Genes, 12.","DOI":"10.3390\/genes12030451"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/5\/1118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:22:53Z","timestamp":1760124173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/5\/1118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,25]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["microorganisms11051118"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11051118","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,25]]}}}