Generic placeholder image

Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Mini-Review Article

Hsp90 as Drug Target Against Bacterial and Fungal Infections

Author(s): Mohammad W. Islam, Samir H. Bloukh, Zehra Edis* and Sabrina A. Gacem

Volume 14, Issue 3, 2020

Page: [153 - 168] Pages: 16

DOI: 10.2174/2212796814666200309113100


Heat shock proteins (Hsps) are a group of proteins that serve to improve cell survival in response to a variety of environmental stresses of the host. In recent years, Hsps gained interest in cancer therapy and as drug target against microbial infections. The antimicrobial resistance especially by Gram-negative pathogens poses a threat to mankind. The pathogen proteins of Hsp family yield Hsp90 inhibitor antibiotic reveal mechanisms that interact with the ADP/ATP-sites of Hsp90. For the present review, we used the databases and websites PubMed, SciFinder, Scopus, ProQuest, Google and Google Scholar. The review discusses the development of Hsp90 inhibitors for bacterial as well as fungal infections and how these inhibitors are being used for clinical trials. A systematic web search analysis was conducted from April to November 2019.

Keywords: Hsp90, chaperone, protein, antibiotic, resistance, cancer, bacteria.

Graphical Abstract
Tissières A, Mitchell HK, Tracy UM. Protein synthesis in salivary glands of Drosophila melanogaster: Relation to chromosome puffs. J Mol Biol 1974; 84(3): 389-98.
[] [PMID: 4219221]
Ritossa F. A new puffing pattern induced by heat shock and DNP in Drosophila. Experientia 1962; 18: 571-3.
Matz JM, LaVoi KP, Moen RJ, Blake MJ. Cold-induced heat shock protein expression in rat aorta and brown adipose tissue. Physiol Behav 1996; 60(5): 1369-74.
[] [PMID: 8916196]
Cao Y, Wang Y, Dai B, et al. Trehalose is an important mediator of Cap1p oxidative stress response in Candida albicans. Biol Pharm Bull 2008; 31(3): 421-5.
[] [PMID: 18310903]
Sreedhar AS, Mihály K, Pató B, et al. Hsp90 inhibition accelerates cell lysis. Anti-Hsp90 ribozyme reveals a complex mechanism of Hsp90 inhibitors involving both superoxide- and Hsp90-dependent events. J Biol Chem 2003; 278(37): 35231-40.
[] [PMID: 12842893]
Bolhassani A, Agi E. Heat shock proteins in infection. Clin Chim Acta 2019; 498: 90-100.
[] [PMID: 31437446]
Sreedhar AS, Csermely P. Heat shock proteins in the regulation of apoptosis: New strategies in tumor therapy: A comprehensive review. Pharmacol Ther 2004; 101(3): 227-57.
[] [PMID: 15031001]
De Maio A. Heat shock proteins: Facts, thoughts, and dreams. Shock 1999; 11(1): 1-12.
[] [PMID: 9921710]
Walter S, Buchner J. Molecular chaperones--cellular machines for protein folding. Angew Chem Int Ed Engl 2002; 41(7): 1098-113.
[<1098::AID-ANIE1098>3.0.CO;2-9] [PMID: 12491239]
Borges JC, Ramos CH. Protein folding assisted by chaperones. Protein Pept Lett 2005; 12(3): 257-61.
[] [PMID: 15777275]
Butler LM, Ferraldeschi R, Armstrong HK, Centenera MM, Workman P. Maximizing the Therapeutic potential of HSP90 inhibitors. Mol Cancer Res 2015; 13(11): 1445-51.
[] [PMID: 26219697]
Lindquist S, Craig EA. The heat-shock proteins. Annu Rev Genet 1988; 22: 631-77.
[] [PMID: 2853609]
Ballinger CA, Connell P, Wu Y, et al. Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol 1999; 19(6): 4535-45.
[] [PMID: 10330192]
Ballinger CA, Hu ZY, Connell P, Patterson C. Identification of CHIP, a novel striated muscle-restricted TPR-containing protein that negatively regulates chaperone functions. FASEB J 1999; 13: A442-2.
Biamonti G, Caceres JF. Cellular stress and RNA splicing. Trends Biochem Sci 2009; 34(3): 146-53.
[] [PMID: 19208481]
Csermely P, Schnaider T, Soti C, Prohászka Z, Nardai G. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther 1998; 79(2): 129-68.
[] [PMID: 9749880]
Matassa DS, Amoroso MR, Maddalena F, Landriscina M, Esposito F. New insights into TRAP1 pathway. Am J Cancer Res 2012; 2(2): 235-48.
[PMID: 22432061]
Wandinger SK, Richter K, Buchner J. The Hsp90 chaperone machinery. J Biol Chem 2008; 283(27): 18473-7.
[] [PMID: 18442971]
Srivastava PK. Peptide-binding heat shock proteins in the endoplasmic reticulum: Role in immune response to cancer and in antigen presentation. Adv Cancer Res 1993; 62: 153-77.
[] [PMID: 8109317]
Pearl LH, Prodromou C. Structure, function, and mechanism of the Hsp90 molecular chaperone. Adv Protein Chem 2001; 59: 157-86.
[] [PMID: 11868271]
Hartl FU, Hayer-Hartl M. Molecular chaperones in the cytosol: From nascent chain to folded protein. Science 2002; 295(5561): 1852-8.
[] [PMID: 11884745]
Rommelaere H, Van Troys M, Gao Y, et al. Eukaryotic cytosolic chaperonin contains t-complex polypeptide 1 and seven related subunits. Proc Natl Acad Sci USA 1993; 90(24): 11975-9.
[] [PMID: 7903455]
Craig EA, Weissman JS, Horwich AL. Heat shock proteins and molecular chaperones: Mediators of protein conformation and turnover in the cell. Cell 1994; 78(3): 365-72.
[] [PMID: 7914834]
Ratzke MC, Mickler BH, Buchner J, Hugel T. Dynamics of heat shock protein 90 C-terminal dimerization is an important part of its conformational cycle, PNAS (Proceeding of the National Academy of Sciences of the United States of America 2010; 107(37): 16101-6.
Chen B, Zhong D, Monteiro A. Comparative genomics and evolution of the HSP90 family of genes across all kingdoms of organisms. BMC Genomics 2006; 7: 156.
[] [PMID: 16780600]
Thomas JG, Baneyx F. ClpB and HtpG facilitate de novo protein folding in stressed Escherichia coli cells. Mol Microbiol 2000; 36(6): 1360-70.
[] [PMID: 10931286]
Neckers L, Tatu U. Molecular chaperones in pathogen virulence: emerging new targets for therapy. Cell Host Microbe 2008; 4(6): 519-27.
[] [PMID: 19064253]
Grenert JP, Sullivan WP, Fadden P, et al. The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J Biol Chem 1997; 272(38): 23843-50.
[] [PMID: 9295332]
Neckers L, Schulte TW, Mimnaugh E. Geldanamycin as a potential anti-cancer agent: Its molecular target and biochemical activity. Invest New Drugs 1999; 17(4): 361-73.
[] [PMID: 10759403]
Scroggins BT, Robzyk K, Wang D, et al. An acetylation site in the middle domain of Hsp90 regulates chaperone function. Mol Cell 2007; 25(1): 151-9.
[] [PMID: 17218278]
Scroggins BT, Neckers L. Post-translational modification of heat-shock protein 90: Impact on chaperone function. Expert Opin Drug Discov 2007; 2(10): 1403-14.
[] [PMID: 23484535]
Li L, An M, Shen H, et al. The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole. Am J Transl Res 2015; 7(12): 2589-602.
[PMID: 26885259]
Cowen LE, Carpenter AE, Matangkasombut O, Fink GR, Lindquist S. Genetic architecture of Hsp90-dependent drug resistance. Eukaryot Cell 2006; 5(12): 2184-8.
[] [PMID: 17056742]
Schulte TW, Akinaga S, Soga S, et al. Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 1998; 3(2): 100-8.
[<0100:ARBTTN>2.3.CO;2] [PMID: 9672245]
Egorin MJ, Lagattuta TF, Hamburger DR, et al. Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxy-geldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats. Cancer Chemother Pharmacol 2002; 49(1): 7-19.
[] [PMID: 11855755.]
Wagner AJ, Chugh R, Rosen LS, et al. A Phase I study of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft-tissue sarcomas. Clin Cancer Res 2013; 19(21): 6020-9.
Ki SW, Ishigami K, Kitahara T, Kasahara K, Yoshida M, Horinouchi S. Radicicol binds and inhibits mammalian ATP citrate lyase. J Biol Chem 2000; 275(50): 39231-6.
[] [PMID: 11007781]
Roe SM, Prodromou C, O’Brien R, Ladbury JE, Piper PW, Pearl LH. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem 1999; 42(2): 260-6.
[] [PMID: 9925731]
Hellwig V, Mayer-Bartschmid A, Müller H, et al. Pochonins A-F, new antiviral and antiparasitic resorcylic acid lactones from Pochonia chlamydosporia var. catenulata. J Nat Prod 2003; 66(6): 829-37.
[] [PMID: 12828470]
Vo CD, Shebert HL, Zikovich S, et al. Repurposing Hsp90 inhibitors as antibiotics targeting histidine kinases. Bioorg Med Chem Lett 2017; 27(23): 5235-44.
[] [PMID: 29110989]
Wang M, Shen G, Blagg BS. Radanamycin, a macrocyclic chimera of radicicol and geldanamycin. Bioorg Med Chem Lett 2006; 16(9): 2459-62.
[] [PMID: 16464590]
Hadden MK, Blagg BS. Synthesis and evaluation of radamide analogues, a chimera of radicicol and geldanamycin. J Org Chem 2009; 74(13): 4697-704.
[] [PMID: 19492825]
Bhat R, Tummalapalli SR, Rotella DP. Progress in the discovery and development of heat shock protein 90 (Hsp90) inhibitors. J Med Chem 2014; 57(21): 8718-28.
[] [PMID: 25141341]
Zhao H, Donnelly AC, Kusuma BR, et al. Engineering an antibiotic to fight cancer: Optimization of the novobiocin scaffold to produce anti-proliferative agents. J Med Chem 2011; 54(11): 3839-53.
[] [PMID: 21553822]
Fujiki H. Two stages of cancer prevention with green tea. J Cancer Res Clin Oncol 1999; 125(11): 589-97.
[] [PMID: 10541965]
Dunbrack RL Jr, Gerloff DL, Bower M, Chen X, Lichtarge O, Cohen FE. Meeting review: The second meeting on the critical assessment of techniques for protein structure prediction (CASP2), Asilomar. Fold Des 1997; 2(2): R27-42.
[] [PMID: 9135979]
Piper PW, Millson SH. Spotlight on the microbes that produce heat shock protein 90-targeting antibiotics. Open Biol 2012; 2(12)120138
[] [PMID: 23271830]
Khalid SA, Duddeck H, Gonzalez-Sierra M. Isolation and characterization of an antimalarial agent of the neem tree Azadirachta indica. J Nat Prod 1989; 52(5): 922-6.
[] [PMID: 2607354]
Senthil Nathan S, Kalaivani K, Chung PG, Murugan K. Effect of neem limonoids on Lactate Dehydrogenase (LDH) of the rice leaffolder, Cnaphalocrocis medinalis (Guenée) (Insecta: Lepidoptera: Pyralidae). Chemosphere 2006; 62(8): 1388-93.
[] [PMID: 16154614]
Uddin SJ, Nahar L, Shilpi JA, et al. Gedunin, a limonoid from Xylocarpus granatum, inhibits the growth of CaCo-2 colon cancer cell line in vitro. Phytother Res 2007; 21(8): 757-61.
[] [PMID: 17450509]
Chiosis G, Timaul MN, Lucas B, et al. A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem Biol 2001; 8(3): 289-99.
[] [PMID: 11306353]
Elfiky A, Saif MW, Beeram M, et al. BIIB021, an oral, synthetic non-ansamycin Hsp90 inhibitor: Phase I experience. J Clin Oncol 2008; 26: 2503-008.
Chandarlapaty S, Sawai A, Ye Q, et al. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res 2008; 14(1): 240-8.
[] [PMID: 18172276]
Whitesell L, Robbins N, Huang DS, et al. Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus. Nat Commun 2019; 10: 402.
Köhler S, Teyssier J, Cloeckaert A, Rouot B, Liautard JP. Participation of the molecular chaperone DnaK in intracellular growth of Brucella suis within U937-derived phagocytes. Mol Microbiol 1996; 20(4): 701-12.
[] [PMID: 8793869]
Konkel ME, Kim BJ, Klena JD, Young CR, Ziprin R. Characterization of the thermal stress response of Campylobacter jejuni. Infect Immun 1998; 66(8): 3666-72.
[] [PMID: 9673247]
Takaya A, Tomoyasu T, Matsui H, Yamamoto T. The DnaK/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is essential for invasion of epithelial cells and survival within macrophages, leading to systemic infection. Infect Immun 2004; 72(3): 1364-73.
[] [PMID: 14977940]
Pizarro-Cerdá J, Cossart P. Bacterial adhesion and entry into host cells. Cell 2006; 124(4): 715-27.
[] [PMID: 16497583]
Taldone T, Gozman A, Maharaj R, Chiosis G. Targeting Hsp90: Small-molecule inhibitors and their clinical development. Curr Opin Pharmacol 2008; 8(4): 370-4.
[] [PMID: 18644253]
Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005; 5(10): 761-72.
[] [PMID: 16175177]
Workman P, Burrows F, Neckers L, Rosen N. Drugging the cancer chaperone HSP90: Combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N Y Acad Sci 2007; 1113: 202-16.
[] [PMID: 17513464]
Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev 2011; 24(2): 247-80.
[] [PMID: 21482725]
Wirk B. Heat shock protein inhibitors for the treatment of fungal infections. Recent Pat Antiinfect Drug Discov 2011; 6(1): 38-44.
[] [PMID: 21192778]
Taipale M, Jarosz DF, Lindquist S. HSP90 at the hub of protein homeostasis: Emerging mechanistic insights. Nat Rev Mol Cell Biol 2010; 11(7): 515-28.
[] [PMID: 20531426]
Leach MD, Klipp E, Cowen LE, Brown AJ. Fungal Hsp90: A biological transistor that tunes cellular outputs to thermal inputs. Nat Rev Microbiol 2012; 10(10): 693-704.
[] [PMID: 22976491]
Shapiro RS, Robbins N, Cowen LE. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 2011; 75(2): 213-67.
[] [PMID: 21646428]
Cowen LE, Singh SD, Köhler JR, et al. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc Natl Acad Sci USA 2009; 106(8): 2818-23.
[] [PMID: 19196973]
Robbins N, Uppuluri P, Nett J, et al. Hsp90 governs dispersion and drug resistance of fungal biofilms. PLoS Pathog 2011; 7(9)e1002257
[] [PMID: 21931556]
Leach MD, Budge S, Walker L, Munro C, Cowen LE, Brown AJ. Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast. PLoS Pathog 2012; 8(12)e1003069
[] [PMID: 23300438]
Roemer T, Krysan DJ. Antifungal drug development: challenges, unmet clinical needs, and new approaches. Cold Spring Harb Perspect Med 2014; 4(5)019703
[] [PMID: 24789878]
Esquivel BD, Smith AR, Zavrel M, White TC. Azole drug import into the pathogenic fungus Aspergillus fumigatus. Antimicrob Agents Chemother 2015; 59(6): 3390-8.
[] [PMID: 25824209]
Singh-Babak SD, Babak T, Diezmann S, et al. Global analysis of the evolution and mechanism of echinocandin resistance in Candida glabrata. PLoS Pathog 2012; 8(5)e1002718
[] [PMID: 22615574]
Lamoth F, Juvvadi PR, Gehrke C, Steinbach WJ. In vitro activity of calcineurin and heat shock protein 90 Inhibitors against Aspergillus fumigatus azole- and echinocandin-resistant strains. Antimicrob Agents Chemother 2013; 57(2): 1035-9.
[] [PMID: 23165466]
LaFayette SL, Collins C, Zaas AK, et al. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90. PLoS Pathog 2010; 6(8)e1001069
[] [PMID: 20865172]
Perlin DS. Current perspectives on echinocandin class drugs. Future Microbiol 2011; 6(4): 441-57.
[] [PMID: 21526945]
te Welscher YM, van Leeuwen MR, de Kruijff B, Dijksterhuis J, Breukink E. Polyene antibiotic that inhibits membrane transport proteins. Proc Natl Acad Sci USA 2012; 109(28): 11156-9.
[] [PMID: 22733749]
Wu S, Wang Y, Liu N, Dong G, Sheng C. Tackling fungal resistance by biofilm inhibitors. J Med Chem 2017; 60(6): 2193-211.
[] [PMID: 28051303]
Juvvadi PR, Lee SC, Heitman J, Steinbach WJ. Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach. Virulence 2017; 8(2): 186-97.
[] [PMID: 27325145]
da Silva Ferreira ME, Heinekamp T, Härtl A, et al. Functional characterization of the Aspergillus fumigatus calcineurin. Fungal Genet Biol 2007; 44(3): 219-30.
[] [PMID: 16990036]
Chen YL, Lehman VN, Lewit Y, Averette AF, Heitman J. Calcineurin governs thermotolerance and virulence of Cryptococcus gattii. G3 (Bethesda) 2013; 3(3): 527-39.
[] [PMID: 23450261]
Cordeiro Rde A, Macedo Rde B, Teixeira CE, et al. The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex. J Med Microbiol 2014; 63(Pt 7): 936-44.
[] [PMID: 24722799]
Pinchai N, Perfect BZ, Juvvadi PR, et al. Aspergillus fumigatus calcipressin CbpA is involved in hyphal growth and calcium homeostasis. Eukaryot Cell 2009; 8(4): 511-9.
[] [PMID: 19252123]
Thevelein JM, Hohmann S. Trehalose synthase: guard to the gate of glycolysis in yeast? Trends Biochem Sci 1995; 20(1): 3-10.
[] [PMID: 7878741]
Elbein AD, Pan YT, Pastuszak I, Carroll D. New insights on trehalose: A multifunctional molecule. Glycobiology 2003; 13(4): 17R-27R.
[] [PMID: 12626396]
Perfect JR, Tenor JL, Miao Y, Brennan RG. Trehalose pathway as an antifungal target. Virulence 2017; 8(2): 143-9.
[] [PMID: 27248439]
Wiemken A. Trehalose in yeast, stress protectant rather than reserve carbohydrate. Antonie van Leeuwenhoek 1990; 58(3): 209-17.
[] [PMID: 2256682]
Benaroudj N, Lee DH, Goldberg AL. Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J Biol Chem 2001; 276(26): 24261-7.
[] [PMID: 11301331]
Zaragoza O, González-Párraga P, Pedreño Y, Alvarez-Peral FJ, Argüelles JC. Trehalose accumulation induced during the oxidative stress response is independent of TPS1 mRNA levels in Candida albicans. Int Microbiol 2003; 6(2): 121-5.
[] [PMID: 12783274]
Petzold EW, Himmelreich U, Mylonakis E, et al. Characterization and regulation of the trehalose synthesis pathway and its importance in the pathogenicity of Cryptococcus neoformans. Infect Immun 2006; 74(10): 5877-87.
[] [PMID: 16988267]
Al-Bader N, Vanier G, Liu H, et al. Role of trehalose biosynthesis in Aspergillus fumigatus development, stress response, and virulence. Infect Immun 2010; 78(7): 3007-18.
[] [PMID: 20439478]
Fillinger S, Chaveroche MK, van Dijck P, et al. Trehalose is required for the acquisition of tolerance to a variety of stresses in the filamentous fungus Aspergillus nidulans. Microbiology 2001; 147(Pt 7): 1851-62.
[] [PMID: 11429462]
Guirao-Abad JP, Sánchez-Fresneda R, Valentín E, Martínez-Esparza M, Argüelles JC. Analysis of validamycin as a potential antifungal compound against Candida albicans. Int Microbiol 2013; 16(4): 217-25.
[PMID: 25102722]
Heung LJ, Luberto C, Del Poeta M. Role of sphingolipids in microbial pathogenesis. Infect Immun 2006; 74(1): 28-39.
[] [PMID: 16368954]
Sharma S, Alfatah M, Bari VK, Rawal Y, Paul S, Ganesan K. Sphingolipid biosynthetic pathway genes FEN1 and SUR4 modulate amphotericin B resistance. Antimicrob Agents Chemother 2014; 58(4): 2409-14.
[] [PMID: 24395234]
Alfatah M, Bari VK, Nahar AS, Bijlani S, Ganesan K. Critical role for CaFEN1 and CaFEN12 of Candida albicans in cell wall integrity and biofilm formation. Sci Rep 2017; 7: 40281.
[] [PMID: 28079132]
Costa E, Silva S, Tavaria F, Pintado M. Antimicrobial and antibiofilm activity of chitosan on the oral pathogen candida albicans. Pathogens 2014; 3(4): 908-19.
[] [PMID: 25513734]
Silva-Dias A, Palmeira-de-Oliveira A, Miranda IM, et al. Anti-biofilm activity of low-molecular weight chitosan hydrogel against Candida species. Med Microbiol Immunol (Berl) 2014; 203(1): 25-33.
[] [PMID: 24013184]
Tan Y, Leonhard M, Moser D, Ma S, Schneider-Stickler B. Inhibition of mixed fungal and bacterial biofilms on silicone by carboxymethyl chitosan. Colloids Surf B Biointerfaces 2016; 148: 193-9.
[] [PMID: 27595894]
Artunduaga Bonilla JJ, Paredes Guerrero DJ, Sánchez Suárez CI, Ortiz López CC, Torres Sáez RG. In vitro antifungal activity of silver nanoparticles against fluconazole-resistant Candida species. World J Microbiol Biotechnol 2015; 31(11): 1801-9.
[] [PMID: 26335058]
Li RF, Wang B, Liu S, et al. Optimization of the expression conditions of CGA-N46 in Bacillus subtilis DB1342(p-3N46) by response surface methodology. Interdiscip Sci 2016; 8(3): 277-83.
[] [PMID: 26341498]
Li RF, Yan XH, Lu YB, et al. Anti-candidal activity of a novel peptide derived from human chromogranin A and its mechanism of action against Candida krusei. Exp Ther Med 2015; 10(5): 1768-76.
[] [PMID: 26640548]
Wu M, Hardwidge PR. Hsp90 Interacts with the Bacterial Effector NleH1. Pathogens 2018; 7(4): 87.
[] [PMID: 30428538]

© 2022 Bentham Science Publishers | Privacy Policy