{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:31:04Z","timestamp":1790469064919,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacterial ClpB is an ATP-dependent disaggregase that belongs to the Hsp100\/Clp subfamily of the AAA+ ATPases and cooperates with the DnaK chaperone system in the reactivation of aggregated proteins, as well as promotes bacterial survival under adverse environmental conditions, including thermal and oxidative stresses. In addition, extensive evidence indicates that ClpB supports the virulence of numerous bacteria, including pathogenic spirochaete Leptospira interrogans responsible for leptospirosis in animals and humans. However, the specific function of ClpB in leptospiral virulence still remains to be fully elucidated. Interestingly, ClpB was predicted as one of the L. interrogans hub proteins interacting with human proteins, and pathogen\u2013host protein interactions are fundamental for successful invasion of the host immune system by bacteria. The aim of this review is to discuss the most important aspects of ClpB\u2019s function in L. interrogans, including contribution of ClpB to leptospiral virulence and pathogenesis of leptospirosis, a zoonotic disease with a significant impact on public health worldwide.<\/jats:p>","DOI":"10.3390\/ijms21186645","type":"journal-article","created":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T09:05:16Z","timestamp":1599815116000},"page":"6645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["AAA+ Molecular Chaperone ClpB in Leptospira interrogans: Its Role and Significance in Leptospiral Virulence and Pathogenesis of Leptospirosis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-3013","authenticated-orcid":false,"given":"Sabina","family":"K\u0119dzierska-Mieszkowska","sequence":"first","affiliation":[{"name":"Department of General and Medical Biochemistry, Faculty of Biology, University of Gda\u0144sk, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-2555","authenticated-orcid":false,"given":"Zbigniew","family":"Arent","sequence":"additional","affiliation":[{"name":"University Centre of Veterinary Medicine, University of Agriculture in Krakow, 30-059 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Costa, F., Hagan, J.E., Calcagno, J., Kane, M., Torgerson, P., Martinez-Silveira, M.S., Stein, C., Abela-Ridder, B., and Ko, A.I. (2015). Global morbidity and mortality of leptospirosis: A systematic review. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003898"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/2046-0481-65-8","article-title":"Seroprevalence of Leptospira Hardjo in the irish suckler cattle population","volume":"65","author":"Ryan","year":"2012","journal-title":"Ir. Vet. J."},{"key":"ref_3","first-page":"369","article-title":"New data concerning diagnosis and control of swine leptospirosis","volume":"87","author":"Pejsak","year":"2012","journal-title":"\u017bycie Weter."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1136\/vr.101239","article-title":"Seroprevalence study of leptospirosis in horses in northern Poland","volume":"172","author":"Arent","year":"2013","journal-title":"Vet. Rec."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1136\/vr.101969","article-title":"Isolation of leptospires from genital tract of sheep","volume":"173","author":"Arent","year":"2013","journal-title":"Vet. Rec."},{"key":"ref_6","first-page":"1","article-title":"Animal models of leptospirosis of mice and hamsters","volume":"8","author":"Santecchia","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/0092-8674(93)90270-Z","article-title":"Signal transduction in the mammalian cell during bacterial attachment and entry","volume":"73","author":"Bliska","year":"1993","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev.cellbio.12.1.221","article-title":"Cross-talk between bacterial pathogens and their host cells","volume":"12","author":"Bliska","year":"1996","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1128\/IAI.05168-11","article-title":"Inactivation of clpB in the pathogen Leptospira interrogans reduces virulence and resistance to stress conditions","volume":"79","author":"Lourdault","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1128\/IAI.01803-14","article-title":"A putative regulatory genetic locus modulates virulence in the pathogen Leptospira interrogans","volume":"82","author":"Eshghi","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1128\/IAI.01546-13","article-title":"High-temperature protein G is an essential virulence factor of Leptospira interrogans","volume":"82","author":"King","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1128\/IAI.01195-12","article-title":"Leptospiral LruA is required for virulence and modulates an interaction with mammalian apolipoprotein AI","volume":"81","author":"Zhang","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1128\/IAI.00466-12","article-title":"Leptospira interrogans catalase is required for resistance to H202 and for virulence","volume":"80","author":"Eshghi","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/mmi.13403","article-title":"A novel flagellar sheath protein, FcpA, determines filamemt coiling translational motility and virulence for the Leptospira spirochete","volume":"101","author":"Wunder","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fontana, C., Lambert, A., Benaroudj, N., Gasparini, D., Gorgette, O., Cachet, N., Bomchil, N., and Picardeau, M. (2016). Analysis of a spontaneous non-motile and avirulent mutant shows that FliM is required for full endoflagella assembly in Leptospira interrogans. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152916"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1128\/IAI.00131-12","article-title":"FlaA proteins in Leptospira interrogans are essential for motility and virulence but are not required for formation of the flagellum sheath","volume":"80","author":"Lambert","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liao, S., Sun, A., Ojcius, D.M., Wu, S., Zhao, J., and Yan, J. (2009). Inactivation of the fliy gene encoding a flagellar motor switch protein attenuates mobility and virulence of Leptospira interrogans strain Lai. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-253"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/infdis\/jit659","article-title":"Identification of collagenase as a critical virulence factor for invasiveness and transmission of pathogenic Leptospira species","volume":"209","author":"Kassegne","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhao, J.-F., Chen, H.-H., Ojcius, D.M., Zhao, X., Sun, D., Ge, Y.-M., Zheng, L.-L., Lin, X., Li, L.-J., and Yan, J. (2013). Identification of Leptospira interrogans phospholipase C as a novel virulence factor responsible for intracellular free calcium ion elevation during macrophage death. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075652"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ristow, P., Bourhy, P., Cruz McBride, F.W., Figueira, C.P., Huerre, M., Ave, P., Girons, I.S., Ko, A.I., and Picardeau, M. (2007). The ompA-lone protein Loa22 is essential for leptospiral virulence. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030097"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rosenberg, E., Delong, E.F., Lory, S., Stackebrandt, E., and Thompson, F. (2014). The family Leptospiraceae. The Prokaryotes, Springer.","DOI":"10.1007\/978-3-642-30138-4"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vincent, A.T., Schiettekatte, O., Goarant, C., Neela, V.K., Bernet, E., Thibeaux, R., Ismail, N., Khalid, M.K.N.M., Amran, F., and Masuzawa, T. (2019). Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007270"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.vetmic.2009.03.012","article-title":"Leptospira and leptospirosis","volume":"140","author":"Adler","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_24","first-page":"283","article-title":"New insights into the pathogenicity of leptospires: Evasion of host defences","volume":"33","author":"Cino","year":"2010","journal-title":"New Microbiol."},{"key":"ref_25","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"Hake","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_26","unstructured":"Farrar, J., Hotez, P., Junghans, T., Kang, G., Lalloo, D., and White, N. (2013). Leptospirosis. Manson\u2019s Tropical Diseases, Saunders Ltd.. [23rd ed.]."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1128\/IAI.74.5.2659-2666.2006","article-title":"LfhA, a novel factor H-binding protein of Leptospira interrogans","volume":"74","author":"Verma","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Stevenson, B., Choy, H.A., Pinne, M., Rotondi, M.L., Miller, M.C., DeMoll, E., Kraiczy, P., Cooley, A.E., Creamer, T.P., and Suchard, M.A. (2007). Leptospira interrogans endostatin-like outer membrane proteins bind fibronectin, laminin and regulators of complement. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0001188"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3389\/fimmu.2016.00623","article-title":"Complement evasion by pathogenic Leptospira","volume":"7","author":"Fraga","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1128\/IAI.00279-10","article-title":"Functional characterization of LcpA, a surface-exposed protein of Leptospira spp. that binds the human complement regulator C4BP","volume":"78","author":"Barbosa","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1128\/IAI.02844-14","article-title":"Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA","volume":"83","author":"Miragaia","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4092","DOI":"10.1128\/IAI.00353-09","article-title":"Plasminogen acquisition and activation at the surface of Leptospira species lead to fibronection degradation","volume":"77","author":"Vieira","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1128\/IAI.01282-09","article-title":"Leptospiral endostatin-like protein A is a bacterial cell surface receptor for human plasminogen","volume":"78","author":"Verma","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.imbio.2016.01.001","article-title":"Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion","volume":"221","author":"Fraga","year":"2016","journal-title":"Immunobiology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Figueira, C.P., Croda, J., Choy, H.A., Haake, D.A., Reis, M.G., Ko, A.I., and Picardeau, M. (2011). Heterologous expression of pathogenic-specific genes ligA and ligB in the saprophyte Leptospira biflexa confers enhanced adhesion to cultured cells and fibronectin. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-129"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Choy, H.A., Kelley, M.M., Croda, J., Matsunaga, J., Babbitt, J.T., Ko, A.I., Picardeau, M., and Haake, D.A. (2011). The multifunctional LigB adhesion binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016879"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6022","DOI":"10.4049\/jimmunol.175.9.6022","article-title":"Differential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells","volume":"175","author":"Nahori","year":"2005","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.4049\/jimmunol.0900506","article-title":"TRL4- and TRL2-medaited B cell response control the clearance of the bacterial pathogen, Leptospira interrogans","volume":"183","author":"Chassin","year":"2009","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrmicro.2017.5","article-title":"Virulence of the zoonotic agent of leptospirosis: Still terra incognita?","volume":"15","author":"Picardeau","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bonhomme, D., Santecchia, I., Vernel-Pauillac, F., Caroff, M., Germon, P., Ben Adler, G.M., Boneca, I.G., and Werts, C. (2020). Leptospiral LPS escapes mouse TLR4 internalization and TRIF-assosiated antimicrobial responses through O antigen and associated lipoproteins. BioRxiv.","DOI":"10.1101\/2020.05.18.101857"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4314","DOI":"10.1128\/IAI.00897-15","article-title":"Leptospira interrogans lpxD homologue is required for thermal acclimatization and virulence","volume":"83","author":"Eshighi","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"28083","DOI":"10.1074\/jbc.274.40.28083","article-title":"ClpB cooperates with DnaK, DnaJ, and GrpE in suppressing protein aggregation","volume":"274","author":"Zolkiewski","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13732","DOI":"10.1073\/pnas.96.24.13732","article-title":"Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network","volume":"96","author":"Goloubinoff","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6934","DOI":"10.1093\/emboj\/18.24.6934","article-title":"Identification of thermolabile Escherichia coli proteins: Prevention and reversion of aggregation by DnaK and ClpB","volume":"18","author":"Mogk","year":"1999","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0092-8674(03)00807-9","article-title":"The structure of ClpB: A molecular chaperone that rescues proteins from an aggregated state","volume":"115","author":"Lee","year":"2003","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.cell.2004.11.027","article-title":"Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB","volume":"119","author":"Weibezahn","year":"2004","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34940","DOI":"10.1074\/jbc.M505653200","article-title":"The amino-terminal domain of ClpB supports binding to strongly aggregated proteins","volume":"280","author":"Barnett","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jmb.2009.11.059","article-title":"Synergistic cooperation between two ClpB isoforms in aggregate reactivation","volume":"396","author":"Nagy","year":"2010","journal-title":"J. Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1128\/jb.173.14.4254-4262.1991","article-title":"ClpB is the Escherichia coli heat shock protein F84.1","volume":"173","author":"Squires","year":"1991","journal-title":"J. Bacteriol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14242","DOI":"10.1021\/bi035573d","article-title":"Structure and function of the middle domain of ClpB from Escherichia coli","volume":"42","author":"Kedzierska","year":"2003","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1110\/ps.8.9.1899","article-title":"Nucleotide-dependent oligomerization of ClpB from Escherichia coli","volume":"8","author":"Zolkiewski","year":"1999","journal-title":"Protein Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1110\/ps.03422604","article-title":"Nucleotide-induced switch in oligomerization of the AAA+ ATPase ClpB","volume":"13","author":"Akoev","year":"2004","journal-title":"Protein Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1002\/prot.24914","article-title":"Examination of the dynamic assembly equilibrium for E. coli ClpB","volume":"83","author":"Lin","year":"2015","journal-title":"Proteins"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6915","DOI":"10.1073\/pnas.1102828108","article-title":"Species-specific collaboration of heat shock proteins (Hsp) 70 and 100 in thermotolerance and protein disaggregation","volume":"108","author":"Miot","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbamcr.2011.07.014","article-title":"The elusive middle domain of Hsp104 and ClpB: Location and function","volume":"1823","author":"DeSantis","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s41586-020-1964-y","article-title":"Processive extrusion of polypeptide loops by a Hsp100 disaggregase","volume":"578","author":"Avellaneda","year":"2020","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1128\/IAI.00698-08","article-title":"Characterization of a unique ClpB protein of Mycoplasma pneumoniae and its impact on growth","volume":"76","author":"Kannan","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1128\/JB.01632-07","article-title":"Role of the Clp system in stress tolerance, biofilm formation, and intracellular invasion in Porphyromonas gingivalis","volume":"190","author":"Capestany","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1128\/JB.186.4.1165-1174.2004","article-title":"ClpB, a novel number of the Listeria monocytogenes CtsR regulon, is involved in virulence but not in general stress tolerance","volume":"186","author":"Chastanet","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/j.1365-2958.2008.06139.x","article-title":"The heat-shock protein ClpB of Francisella tularensis is involved in stress tolerance and is required for multiplication in target organs of infected mice","volume":"67","author":"Meibom","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Krajewska, J., Arent, Z., Wi\u0119ckowski, D., Zolkiewski, M., and K\u0119dzierska-Mieszkowska, S. (2016). Immunoreactivity of the AAA+ chaperone ClpB from Leptospira interrogans with sera from Leptospira-infected animals. BMC Microbiol., 16.","DOI":"10.1186\/s12866-016-0774-8"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1590\/S1415-47572007000200012","article-title":"A preliminary survey of M. hyopneumoniae virulence factors based on comparative genomic analysis","volume":"30","author":"Ferreria","year":"2007","journal-title":"Genet. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.diagmicrobio.2007.04.017","article-title":"Detection of the host immune response to Burkholderia mallei heat-shock proteins GroEL and DnaK in a glanders patient and infected mice","volume":"59","author":"Amemiya","year":"2007","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1002\/pmic.200401123","article-title":"Proteomic analysis of anti-Francisella tularensis LVS antibody response in murine model of tularemia","volume":"5","author":"Brychta","year":"2005","journal-title":"Proteomics"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Krajewska, J., Modrak-W\u00f3jcik, A., Arent, Z., Wi\u0119ckowski, D., Zolkiewski, M., Bzowska, A., and K\u0119dzierska-Mieszkowska, S. (2017). Characterization of the molecular chaperone ClpB from the pathogenic spirochaete Leptospira interrogans. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181118"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5804","DOI":"10.1074\/jbc.M109349200","article-title":"Roles of the two ATP binding sites of ClpB from Thermus thermophilus","volume":"277","author":"Watanabe","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8070","DOI":"10.1128\/JB.00404-06","article-title":"Structural and functional conversion of molecular chaperone ClpB from the Gram-positive halophilic lactic acid bacterium Tetragenococcus halophilus mediated by ATP and stress","volume":"188","author":"Sugimoto","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_68","first-page":"1","article-title":"Protein aggregation in Ehrlichia chaffeensis during infection of mammalian Wells","volume":"364","author":"Cheng","year":"2017","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1038\/emi.2017.93","article-title":"A leptospiral AAA+ chaperone-Ntn peptidase complex, HslUV, contributes to the intracellular survival of Leptospira interrogans in hosts and the transmission of leptospirosis","volume":"6","author":"Dong","year":"2017","journal-title":"Emerg. Microbes Infect."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Krajewska, J., Arent, Z., Zolkiewski, M., and K\u0119dzierska-Mieszkowska, S. (2018). Isolation and identification of putative protein substrate of the AAA+ chaperone chaperone ClpB from pathogenic spirochaete Leptospira interrogans. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041234"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Patarakul, K., Lo, M., and Adler, B. (2010). Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-31"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1038\/s41598-018-38329-1","article-title":"Inferring pathogen-host interactions between Leptospira interrogans and Homo sapiens using network theory","volume":"9","author":"Kumar","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3844\/ajbbsp.2014.208.210","article-title":"Are heat shock proteins druggable candidates?","volume":"10","author":"Zininga","year":"2014","journal-title":"Am. J. Biochem. Biotechnol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Shonhai, A., and Blatch, G.L. (2014). Role of Hsp70s in development and pathogenicity of Plasmodium species. Heat Shock Proteins of Malaria, Springer.","DOI":"10.1007\/978-94-007-7438-4"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zininga, T., and Shonhai, A. (2019). Small molecule inhibitors targeting the heat shock protein system of human obligate protozoan parasites. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235930"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6645\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:08:57Z","timestamp":1760177337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,11]]},"references-count":75,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21186645"],"URL":"https:\/\/doi.org\/10.3390\/ijms21186645","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,11]]}}}