FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Infection and immunity2001; 69(12); 7616-7624; doi: 10.1128/IAI.69.12.7616-7624.2001

Molecular characterization of thermoinduced immunogenic proteins Q1p42 and Hsp15 of Leptospira interrogans.

Abstract: Leptospira interrogans is a mammalian pathogen which must adapt to a range of new environmental conditions including temperature change when it infects new hosts. In vitro studies of organisms cultured at 30 degrees C and shifted to 37 degrees C for 5 to 7 days have confirmed that synthesis of several proteins involved in equine infection is regulated in response to temperature change (J. E. Nally, J. F. Timoney, and B. Stevenson, Infect. Immun. 69:400-404, 2001). In order to specifically identify antigenic proteins upregulated at 37 degrees C, groups of three ponies were immunized with organisms shifted to 37 degrees C for 5 to 7 days or with organisms maintained at 30 degrees C. A lambda ZAP II genomic DNA library was screened with the pool of antisera to organisms shifted to 37 degrees C. Clones reactive with this pool but unreactive with the pool of pony antisera to organisms cultured at 30 degrees C were selected for further analysis. Sequence analysis of the first two clones identified open reading frames for proteins designated Qlp42 and Hsp15. Qlp42 is predicted to be an outer membrane lipoprotein. Its synthesis was upregulated when cultures were shifted from 30 to 37 degrees C and downregulated when cultures were shifted from 37 to 30 degrees C. Although the predicted molecular mass of Qlp42 is 39.8 kDa for the mature protein, Qlp42-specific equine antiserum was reactive with two bands of 30 and 29.5 kDa. Hsp15 is a stress response protein and a member of the Hsp20/alpha-crystallin family. PCR detected homologues of qlp42 and hsp15 in pathogenic serovars of L. interrogans but not in the nonpathogenic Leptospira biflexa. Enzyme-linked immunosorbent assays of antibody in convalescent sera from mares naturally infected with L. interrogans suggest that Qlp42 is expressed during leptospiral infection.
Get Full Text
Publication Date: 2001-11-14 PubMed ID: 11705941PubMed Central: PMC98855DOI: 10.1128/IAI.69.12.7616-7624.2001Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study focuses on the genetic analysis and characterization of two proteins, Q1p42 and Hsp15, in the pathogen Leptospira interrogans. They found that these two proteins are involved and adapt to temperature changes when the pathogen infects new hosts.

Research Methodology

  • The researchers started off studying the organisms at a controlled 30 degrees Celsius and then adjusted the temperature to 37 degrees for between 5 to 7 days.
  • This study was in an effort to identify the proteins that were being activated at the higher temperature. To do this, they immunized ponies in groups of three, with the organisms that had been heated to 37 degrees Celsius for the said duration, and others with organisms kept at 30 degrees Celsius.
  • To identify the antigenic proteins that were active at the higher temperature of 37 degrees, the researchers used a lambda ZAP II genomic DNA library and screened it with a pool of antisera from organisms that were heated up to 37 degrees Celsius.
  • They selected clones that reacted with this pool for further analysis but did not react with the pony antisera to organisms cultured at 30 degrees Celsius.

Findings

  • The results from the sequence analysis identified two proteins designated as Qlp42 and Hsp15 from the selected clones.
  • Qlp42, which was found to be an outer membrane lipoprotein, showed increased synthesis when temperatures moved from 30 to 37 degrees Celsius, and a decrease was observed when the temperatures were reduced back to 30 degrees Celsius.
  • Another interesting finding was that even if Qlp42 is predicted to be 39.8 kDa for the mature protein, the Qlp42-specific equine antiserum reacted with two bands of 30 and 29.5 kDa.
  • Hsp15 was identified to be a stress response protein and also a member of the Hsp20/alpha-crystallin family.
  • PCR detected homologues of qlp42 and hsp15 in pathogenic serovars of Leptospira interrogans but not in the nonpathogenic Leptospira biflexa.
  • An enzyme-linked immunosorbent assay of antibody in convalescent sera from mares naturally infected with Leptospira interrogans hinted that Qlp42 is likely expressed during leptospiral infection.

Conclusion and Potential Implications

The research concludes that the proteins Q1p42 and Hsp15 are critical in the adaptation of Leptospira interrogans to new environmental conditions when switching hosts. Understanding this adaptive mechanism can help develop effective vaccines to counter infections. It is also suggested that the temperature inducement of these proteins might be a key factor in the pathogenesis of the Leptospira interrogans infection.

Cite This Article

APA
Nally JE, Artiushin S, Timoney JF. (2001). Molecular characterization of thermoinduced immunogenic proteins Q1p42 and Hsp15 of Leptospira interrogans. Infect Immun, 69(12), 7616-7624. https://doi.org/10.1128/IAI.69.12.7616-7624.2001

Publication

Infection and immunity
ISSN: 0019-9567
NlmUniqueID: 0246127
Country: United States
Language: English
Volume: 69
Issue: 12
Pages: 7616-7624

Researcher Affiliations

Nally, J E
  • Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546-0099, USA.
Artiushin, S
    Timoney, J F

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Antibodies, Bacterial / immunology
      • Antibody Specificity
      • Antigens, Bacterial / genetics
      • Antigens, Bacterial / immunology
      • Bacterial Outer Membrane Proteins / genetics
      • Bacterial Outer Membrane Proteins / immunology
      • Base Sequence
      • Convalescence
      • DNA-Binding Proteins / genetics
      • DNA-Binding Proteins / immunology
      • Escherichia coli Proteins
      • Female
      • Gene Expression Regulation, Bacterial
      • Genomic Library
      • Heat-Shock Proteins / genetics
      • Heat-Shock Proteins / immunology
      • Horse Diseases / blood
      • Horse Diseases / immunology
      • Horses
      • Hot Temperature
      • Leptospira interrogans / genetics
      • Leptospira interrogans / immunology
      • Leptospirosis / blood
      • Leptospirosis / immunology
      • Leptospirosis / veterinary
      • Lipoproteins / genetics
      • Lipoproteins / immunology
      • Molecular Sequence Data
      • Sequence Analysis, DNA
      • Sequence Homology, Amino Acid
      • Up-Regulation

      References

      This article includes 27 references
      1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool.. J Mol Biol 1990 Oct 5;215(3):403-10.
        pubmed: 2231712doi: 10.1016/s0022-2836(05)80360-2google scholar: lookup
      2. Bateman A, Birney E, Durbin R, Eddy SR, Howe KL, Sonnhammer EL. The Pfam protein families database.. Nucleic Acids Res 2000 Jan 1;28(1):263-6.
        pmc: PMC102420pubmed: 10592242doi: 10.1093/nar/28.1.263google scholar: lookup
      3. Chang Z, Primm TP, Jakana J, Lee IH, Serysheva I, Chiu W, Gilbert HF, Quiocho FA. Mycobacterium tuberculosis 16-kDa antigen (Hsp16.3) functions as an oligomeric structure in vitro to suppress thermal aggregation.. J Biol Chem 1996 Mar 22;271(12):7218-23.
        pubmed: 8636160
      4. Donahue JM. Equine leptospirosis. Equine Dis Q 2001;9:5.
      5. Ehrnsperger M, Gräber S, Gaestel M, Buchner J. Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation.. EMBO J 1997 Jan 15;16(2):221-9.
        pmc: PMC1169629pubmed: 9029143doi: 10.1093/emboj/16.2.221google scholar: lookup
      6. Faine S, Adler B, Bolin C, Perolat P. Leptospira and leptospirosis. 2nd ed. Melbourne, Australia: MediSci; 1999.
      7. Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, White O, Ketchum KA, Dodson R, Hickey EK, Gwinn M, Dougherty B, Tomb JF, Fleischmann RD, Richardson D, Peterson J, Kerlavage AR, Quackenbush J, Salzberg S, Hanson M, van Vugt R, Palmer N, Adams MD, Gocayne J, Weidman J, Utterback T, Watthey L, McDonald L, Artiach P, Bowman C, Garland S, Fuji C, Cotton MD, Horst K, Roberts K, Hatch B, Smith HO, Venter JC. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi.. Nature 1997 Dec 11;390(6660):580-6.
        pubmed: 9403685doi: 10.1038/37551google scholar: lookup
      8. Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Fujii C, Garland S, Hatch B, Horst K, Roberts K, Sandusky M, Weidman J, Smith HO, Venter JC. Complete genome sequence of Treponema pallidum, the syphilis spirochete.. Science 1998 Jul 17;281(5375):375-88.
        pubmed: 9665876doi: 10.1126/science.281.5375.375google scholar: lookup
      9. Haake DA. Spirochaetal lipoproteins and pathogenesis.. Microbiology (Reading) 2000 Jul;146 ( Pt 7)(Pt 7):1491-1504.
        pmc: PMC2664406pubmed: 10878114doi: 10.1099/00221287-146-7-1491google scholar: lookup
      10. Haake DA, Martinich C, Summers TA, Shang ES, Pruetz JD, McCoy AM, Mazel MK, Bolin CA. Characterization of leptospiral outer membrane lipoprotein LipL36: downregulation associated with late-log-phase growth and mammalian infection.. Infect Immun 1998 Apr;66(4):1579-87.
        pmc: PMC108091pubmed: 9529084doi: 10.1128/iai.66.4.1579-1587.1998google scholar: lookup
      11. Hayashi S, Wu HC. Lipoproteins in bacteria.. J Bioenerg Biomembr 1990 Jun;22(3):451-71.
        pubmed: 2202727doi: 10.1007/bf00763177google scholar: lookup
      12. Horwitz J. Alpha-crystallin can function as a molecular chaperone.. Proc Natl Acad Sci U S A 1992 Nov 1;89(21):10449-53.
        pmc: PMC50356pubmed: 1438232doi: 10.1073/pnas.89.21.10449google scholar: lookup
      13. Johnson RC, Harris VG. Differentiation of pathogenic and saprophytic letospires. I. Growth at low temperatures.. J Bacteriol 1967 Jul;94(1):27-31.
        pmc: PMC251866pubmed: 6027998doi: 10.1128/jb.94.1.27-31.1967google scholar: lookup
      14. Jusuf SD. Proteins of Leptospira interrogans serovar pomona type kennewicki reactive with serum antibodies of aborting mares and their fetuses. Doctoral dissertation. Lexington: University of Kentucky; 1997.
      15. Kim KK, Kim R, Kim SH. Crystal structure of a small heat-shock protein.. Nature 1998 Aug 6;394(6693):595-9.
        pubmed: 9707123doi: 10.1038/29106google scholar: lookup
      16. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.. Nature 1970 Aug 15;227(5259):680-5.
        pubmed: 5432063doi: 10.1038/227680a0google scholar: lookup
      17. Lee GJ, Pokala N, Vierling E. Structure and in vitro molecular chaperone activity of cytosolic small heat shock proteins from pea.. J Biol Chem 1995 May 5;270(18):10432-8.
        pubmed: 7737977doi: 10.1074/jbc.270.18.10432google scholar: lookup
      18. Lee GJ, Roseman AM, Saibil HR, Vierling E. A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state.. EMBO J 1997 Feb 3;16(3):659-71.
        pmc: PMC1169668pubmed: 9034347doi: 10.1093/emboj/16.3.659google scholar: lookup
      19. Levett PN. Leptospirosis.. Clin Microbiol Rev 2001 Apr;14(2):296-326.
        pmc: PMC88975pubmed: 11292640doi: 10.1128/cmr.14.2.296-326.2001google scholar: lookup
      20. Merck KB, Groenen PJ, Voorter CE, de Haard-Hoekman WA, Horwitz J, Bloemendal H, de Jong WW. Structural and functional similarities of bovine alpha-crystallin and mouse small heat-shock protein. A family of chaperones.. J Biol Chem 1993 Jan 15;268(2):1046-52.
        pubmed: 8093449
      21. Nally JE, Timoney JF, Stevenson B. Temperature-regulated protein synthesis by Leptospira interrogans.. Infect Immun 2001 Jan;69(1):400-4.
        pmc: PMC97896pubmed: 11119530doi: 10.1128/iai.69.1.400-404.2001google scholar: lookup
      22. Parma AE, Cerone SI, Sansinanea SA. Biochemical analysis by SDS-PAGE and western blotting of the antigenic relationship between Leptospira and equine ocular tissues.. Vet Immunol Immunopathol 1992 Jun;33(1-2):179-85.
        pubmed: 1632080doi: 10.1016/0165-2427(92)90045-rgoogle scholar: lookup
      23. Parma AE, Santisteban CG, Villalba JS, Bowden RA. Experimental demonstration of an antigenic relationship between Leptospira and equine cornea.. Vet Immunol Immunopathol 1985 Nov;10(2-3):215-24.
        pubmed: 4082476doi: 10.1016/0165-2427(85)90048-0google scholar: lookup
      24. Stamm LV, Gherardini FC, Parrish EA, Moomaw CR. Heat shock response of spirochetes.. Infect Immun 1991 Apr;59(4):1572-5.
        pmc: PMC257880pubmed: 2004832doi: 10.1128/iai.59.4.1572-1575.1991google scholar: lookup
      25. Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen.. Nature 2000 Aug 31;406(6799):959-64.
        pubmed: 10984043doi: 10.1038/35023079google scholar: lookup
      26. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.. Nucleic Acids Res 1994 Nov 11;22(22):4673-80.
        pmc: PMC308517pubmed: 7984417doi: 10.1093/nar/22.22.4673google scholar: lookup
      27. White O, Eisen JA, Heidelberg JF, Hickey EK, Peterson JD, Dodson RJ, Haft DH, Gwinn ML, Nelson WC, Richardson DL, Moffat KS, Qin H, Jiang L, Pamphile W, Crosby M, Shen M, Vamathevan JJ, Lam P, McDonald L, Utterback T, Zalewski C, Makarova KS, Aravind L, Daly MJ, Minton KW, Fleischmann RD, Ketchum KA, Nelson KE, Salzberg S, Smith HO, Venter JC, Fraser CM. Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1.. Science 1999 Nov 19;286(5444):1571-7.
        pmc: PMC4147723pubmed: 10567266doi: 10.1126/science.286.5444.1571google scholar: lookup

      Citations

      This article has been cited 33 times.
      1. Fernandes LGV, Putz EJ, Stasko J, Lippolis JD, Nascimento ALTO, Nally JE. Evaluation of LipL32 and LigA/LigB Knockdown Mutants in Leptospira interrogans Serovar Copenhageni: Impacts to Proteome and Virulence. Front Microbiol 2021;12:799012.
        doi: 10.3389/fmicb.2021.799012pubmed: 35185824google scholar: lookup
      2. Nally JE, Hornsby RL, Alt DP. Antigen-Specific Urinary Immunoglobulin in Reservoir Hosts of Leptospirosis. Vet Sci 2021 Sep 1;8(9).
        doi: 10.3390/vetsci8090178pubmed: 34564572google scholar: lookup
      3. Putz EJ, Sivasankaran SK, Fernandes LGV, Brunelle B, Lippolis JD, Alt DP, Bayles DO, Hornsby RL, Nally JE. Distinct transcriptional profiles of Leptospira borgpetersenii serovar Hardjo strains JB197 and HB203 cultured at different temperatures. PLoS Negl Trop Dis 2021 Apr;15(4):e0009320.
        doi: 10.1371/journal.pntd.0009320pubmed: 33826628google scholar: lookup
      4. Putz EJ, Nally JE. Investigating the Immunological and Biological Equilibrium of Reservoir Hosts and Pathogenic Leptospira: Balancing the Solution to an Acute Problem?. Front Microbiol 2020;11:2005.
        doi: 10.3389/fmicb.2020.02005pubmed: 32922382google scholar: lookup
      5. Nally JE, Wilson-Welder JH, Hornsby RL, Palmer MV, Alt DP. Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated Cellular Immune Responsiveness. Front Cell Infect Microbiol 2018;8:66.
        doi: 10.3389/fcimb.2018.00066pubmed: 29594063google scholar: lookup
      6. Nally JE, Grassmann AA, Planchon S, Sergeant K, Renaut J, Seshu J, McBride AJ, Caimano MJ. Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals. Front Cell Infect Microbiol 2017;7:362.
        doi: 10.3389/fcimb.2017.00362pubmed: 28848720google scholar: lookup
      7. Haake DA, Zückert WR. The leptospiral outer membrane. Curr Top Microbiol Immunol 2015;387:187-221.
        doi: 10.1007/978-3-662-45059-8_8pubmed: 25388136google scholar: lookup
      8. Pinne M, Haake DA. LipL32 Is a Subsurface Lipoprotein of Leptospira interrogans: presentation of new data and reevaluation of previous studies. PLoS One 2013;8(1):e51025.
        doi: 10.1371/journal.pone.0051025pubmed: 23323152google scholar: lookup
      9. Verma A, Matsunaga J, Artiushin S, Pinne M, Houwers DJ, Haake DA, Stevenson B, Timoney JF. Antibodies to a novel leptospiral protein, LruC, in the eye fluids and sera of horses with Leptospira-associated uveitis. Clin Vaccine Immunol 2012 Mar;19(3):452-6.
        doi: 10.1128/CVI.05524-11pubmed: 22237897google scholar: lookup
      10. Eshghi A, Pinne M, Haake DA, Zuerner RL, Frank A, Cameron CE. Methylation and in vivo expression of the surface-exposed Leptospira interrogans outer-membrane protein OmpL32. Microbiology (Reading) 2012 Mar;158(Pt 3):622-635.
        doi: 10.1099/mic.0.054767-0pubmed: 22174381google scholar: lookup
      11. Cerqueira GM, Souza NM, Araújo ER, Barros AT, Morais ZM, Vasconcellos SA, Nascimento AL. Development of transcriptional fusions to assess Leptospira interrogans promoter activity. PLoS One 2011 Mar 18;6(3):e17409.
        doi: 10.1371/journal.pone.0017409pubmed: 21445252google scholar: lookup
      12. Evangelista KV, Coburn J. Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. Future Microbiol 2010 Sep;5(9):1413-25.
        doi: 10.2217/fmb.10.102pubmed: 20860485google scholar: lookup
      13. Patarakul K, Lo M, Adler B. Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum. BMC Microbiol 2010 Jan 29;10:31.
        doi: 10.1186/1471-2180-10-31pubmed: 20113507google scholar: lookup
      14. Lo M, Cordwell SJ, Bulach DM, Adler B. Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature. PLoS Negl Trop Dis 2009 Dec 8;3(12):e560.
        doi: 10.1371/journal.pntd.0000560pubmed: 19997626google scholar: lookup
      15. Beck M, Malmström JA, Lange V, Schmidt A, Deutsch EW, Aebersold R. Visual proteomics of the human pathogen Leptospira interrogans. Nat Methods 2009 Nov;6(11):817-23.
        doi: 10.1038/nmeth.1390pubmed: 19838170google scholar: lookup
      16. Eshghi A, Cullen PA, Cowen L, Zuerner RL, Cameron CE. Global proteome analysis of Leptospira interrogans. J Proteome Res 2009 Oct;8(10):4564-78.
        doi: 10.1021/pr9004597pubmed: 19663501google scholar: lookup
      17. Vieira ML, Pimenta DC, de Morais ZM, Vasconcellos SA, Nascimento AL. Proteome analysis of Leptospira interrogans virulent strain. Open Microbiol J 2009 May 7;3:69-74.
        doi: 10.2174/1874285800903010069pubmed: 19590580google scholar: lookup
      18. Pinne M, Haake DA. A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans. PLoS One 2009 Jun 29;4(6):e6071.
        doi: 10.1371/journal.pone.0006071pubmed: 19562037google scholar: lookup
      19. Monahan AM, Callanan JJ, Nally JE. Proteomic analysis of Leptospira interrogans shed in urine of chronically infected hosts. Infect Immun 2008 Nov;76(11):4952-8.
        doi: 10.1128/IAI.00511-08pubmed: 18765721google scholar: lookup
      20. Atzingen MV, Barbosa AS, De Brito T, Vasconcellos SA, de Morais ZM, Lima DM, Abreu PA, Nascimento AL. Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection. BMC Microbiol 2008 Apr 29;8:70.
        doi: 10.1186/1471-2180-8-70pubmed: 18445272google scholar: lookup
      21. Wang Z, Jin L, Wegrzyn A. Leptospirosis vaccines. Microb Cell Fact 2007 Dec 11;6:39.
        doi: 10.1186/1475-2859-6-39pubmed: 18072968google scholar: lookup
      22. Matsunaga J, Lo M, Bulach DM, Zuerner RL, Adler B, Haake DA. Response of Leptospira interrogans to physiologic osmolarity: relevance in signaling the environment-to-host transition. Infect Immun 2007 Jun;75(6):2864-74.
        doi: 10.1128/IAI.01619-06pubmed: 17371863google scholar: lookup
      23. Nally JE, Whitelegge JP, Bassilian S, Blanco DR, Lovett MA. Characterization of the outer membrane proteome of Leptospira interrogans expressed during acute lethal infection. Infect Immun 2007 Feb;75(2):766-73.
        doi: 10.1128/IAI.00741-06pubmed: 17101664google scholar: lookup
      24. Lo M, Bulach DM, Powell DR, Haake DA, Matsunaga J, Paustian ML, Zuerner RL, Adler B. Effects of temperature on gene expression patterns in Leptospira interrogans serovar Lai as assessed by whole-genome microarrays. Infect Immun 2006 Oct;74(10):5848-59.
        doi: 10.1128/IAI.00755-06pubmed: 16988264google scholar: lookup
      25. Qin JH, Sheng YY, Zhang ZM, Shi YZ, He P, Hu BY, Yang Y, Liu SG, Zhao GP, Guo XK. Genome-wide transcriptional analysis of temperature shift in L. interrogans serovar lai strain 56601. BMC Microbiol 2006 Jun 9;6:51.
        doi: 10.1186/1471-2180-6-51pubmed: 16762078google scholar: lookup
      26. Verma A, Artiushin S, Matsunaga J, Haake DA, Timoney JF. LruA and LruB, novel lipoproteins of pathogenic Leptospira interrogans associated with equine recurrent uveitis. Infect Immun 2005 Nov;73(11):7259-66.
        doi: 10.1128/IAI.73.11.7259-7266.2005pubmed: 16239521google scholar: lookup
      27. Matsunaga J, Sanchez Y, Xu X, Haake DA. Osmolarity, a key environmental signal controlling expression of leptospiral proteins LigA and LigB and the extracellular release of LigA. Infect Immun 2005 Jan;73(1):70-8.
        doi: 10.1128/IAI.73.1.70-78.2005pubmed: 15618142google scholar: lookup
      28. Haake DA, Suchard MA, Kelley MM, Dundoo M, Alt DP, Zuerner RL. Molecular evolution and mosaicism of leptospiral outer membrane proteins involves horizontal DNA transfer. J Bacteriol 2004 May;186(9):2818-28.
        doi: 10.1128/JB.186.9.2818-2828.2004pubmed: 15090524google scholar: lookup
      29. Artiushin S, Timoney JF, Nally J, Verma A. Host-inducible immunogenic sphingomyelinase-like protein, Lk73.5, of Leptospira interrogans. Infect Immun 2004 Feb;72(2):742-9.
        doi: 10.1128/IAI.72.2.742-749.2004pubmed: 14742516google scholar: lookup
      30. Fernandes LGV, Nascimento ALTO, Nally JE. Induced protein expression in Leptospira spp. and its application to CRISPR/Cas9 mutant generation. Sci Rep 2025 Feb 5;15(1):4334.
        doi: 10.1038/s41598-025-88633-wpubmed: 39910196google scholar: lookup
      31. Ribeiro PDS, Stasko J, Shircliff A, Fernandes LG, Putz EJ, Andreasen C, Azevedo V, Ristow P, Nally JE. Investigations into the growth and formation of biofilm by Leptospira biflexa at temperatures encountered during infection. Biofilm 2025 Jun;9:100243.
        doi: 10.1016/j.bioflm.2024.100243pubmed: 39758814google scholar: lookup
      32. Hamond C, Adam EN, Stone NE, LeCount K, Anderson T, Putz EJ, Camp P, Hicks J, Stuber T, van der Linden H, Bayles DO, Sahl JW, Schlater LK, Wagner DM, Nally JE. Identification of equine mares as reservoir hosts for pathogenic species of Leptospira. Front Vet Sci 2024;11:1346713.
        doi: 10.3389/fvets.2024.1346713pubmed: 38784659google scholar: lookup
      33. Hornsby RL, Alt DP, Nally JE. Isolation and propagation of leptospires at 37 °C directly from the mammalian host. Sci Rep 2020 Jun 15;10(1):9620.
        doi: 10.1038/s41598-020-66526-4pubmed: 32541841google scholar: lookup
      Subscribe to our newsletter
      Join 99,970 horse owners like you who receive our email updates on horse health and nutrition.