The central goal of my laboratory is to develop peptide-based therapeutics with novel antimicrobial mechanisms to overcome bacterial resistance to traditional antibiotics. Antibiotic resistance constitutes a global health crisis, which threatens to reverse many advances in the field of medicine. In that regard, cationic antimicrobial peptides (AMPs) are a class of antimicrobial agents that are very promising against multidrug-resistant bacteria due to their membrane-disruption mechanisms, the lower propensity to invoke selection of resistance compared to conventional antibiotics, and bacterial killing properties that are typically not affected by the metabolic state of the bacterial cells. However, cationic peptides present several limitations related to the types of biological environments and susceptibility to protease digestion. While sequence optimization or de novo engineering can help overcome some of these limitations, AMP design is currently done mainly by trial and error based on the principle of cationic amphipathicity. Thus, the future of this promising class of peptides depends on the ability to design AMPs for specific applications by dissecting the AMP functional motifs to elucidate their differential roles in antimicrobial properties and host toxicity. This can be accomplished by establishing a general framework for cationic peptide design, based on iterative structure-function (spectrum of activity, drug affinity, bacterial killing and resistance mechanisms, and toxicity to mammalian cells) relationship to minimize peptide length required for low or absence of toxicity to mammalian cells and high therapeutic index. The application of these peptides can be extended to the treatment of cancer and viral infections.
1993 | City College of the University of New York | BS, Anthropology and Biochemistry
1996 | City College of the University of New York | MA, Biochemistry
2006 | University of Pittsburgh School of Medicine | PhD, Microbiology and Molecular Genetics
2008 | University of Pittsburgh School of Medicine | MD, Medicine
EOH 3210, Pathophysiology of environmental disease
Xiang W, Clemenza P, Klousnitzer J, Chen J, Qin W, Tristram-Nagle S, Doi Y, Di PY, and Deslouches B. Rational Framework for the Design of Trp- and Arg-Rich Peptide Antibiotics Against Multidrug-Resistant Bacteria.Front. Microbiol. 23 May 2022. doi: 10.3389/fmicb.2022.889791
Beumera JH, Guo J, Ray EC, Scemama J, Parise RA, Deslouches B, Steckbeck JD, Montelaro RC, Eiseman JL. Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice. Curr Clin Pharmacol. 2021:10.2174/1574884715666200810094201. doi: 10.2174/1574884715666200810094201. Epub ahead of print. PMID: 32778037; PMCID: PMC8083974.
Deslouches B, Montelaro RC, Urish KL, Di YP. Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria. Pharmaceutics. 2020 May 30;12(6):501. doi: 10.3390/pharmaceutics12060501. PMID: 32486228; PMCID: PMC7357155.
Di YP, LinQ, Chen C, Montelaro RC, Doi Y, Deslouches B. Enhanced therapeutic index of an antimicrobial peptide. Sci. Adv. 2020; May 1;6(18):eaay6817. PMID: 32426473
Mandell JB, A Koch J, Deslouches B, Urish KL. Direct antimicrobial activity of cationic amphipathic peptide WLBU2 against Staphylococcus aureus biofilms is enhanced in physiologic buffered saline. J Orthop Res. 2020 Dec;38(12):2657-2663. doi: 10.1002/jor.24765. Epub 2020 Jun 9. PMID: 32484998; PMCID: PMC7665995.
Heinrich F, Salyapongse A, Kumagai A, Dupuy FG, Shukla K, Penk A, Huster D, Ernst RK, Pavlova A, Gumbart JC, Deslouches B, Di YP, Tristram-Nagle S. Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes. Chemistry. 2020 May 15;26(28):6247-6256. doi: 10.1002/chem.202000212. Epub 2020 Apr 28. PMID: 32166806; PMCID: PMC8146162.
Jiang S, Deslouches B, Chen C, Di ME, Di YP. Antibacterial Properties and Efficacy of a Novel SPLUNC1-Derived Antimicrobial Peptide, a4-Short, in a Murine Model of Respiratory Infection. mBio. 2019 Apr 9;10(2):e00226-19. doi: 10.1128/mBio.00226-19. PMID: 30967458; PMCID: PMC6456746.
Kumagai A , Dupuy FG , Arsov Z , Elhady Y , Moody D, Ernst RK, Deslouches B , Montelaro RC , Peter Di Y , Tristram-Nagle S . Elastic behavior of model membranes with antimicrobial peptides depends on lipid specificity and d-enantiomers. Soft Matter. 2019 Feb 20;15(8):1860-1868. doi: 10.1039/c8sm02180e. PMID: 30702120; PMCID: PMC7485610.
Yu Z, Deslouches B, Walton WG, Redinbo MR, Di YP. Enhanced biofilm prevention activity of a SPLUNC1-derived antimicrobial peptide against Staphylococcus aureus. PLoS One. 2018 Sep 14;13(9):e0203621. doi: 10.1371/journal.pone.0203621. PMID: 30216370; PMCID: PMC6138395.
Deslouches B, Di YP. Antimicrobial Peptides: A Potential Therapeutic Option for Surgical Site Infections. Clin Surg. 2017 Nov;2:1740. Epub 2017 Nov 16. PMID: 30135956; PMCID: PMC6101250.
Lin Q, Deslouches B, Montelaro RC, Di YP. Prevention of ESKAPE pathogen biofilm formation by antimicrobial peptides WLBU2 and LL37. Int J Antimicrob Agents. 2018 Nov;52(5):667-672. doi: 10.1016/j.ijantimicag.2018.04.019. Epub 2018 May 10. PMID: 29753132; PMCID: PMC6230315.
Mandell JB, Deslouches B, Montelaro RC, Shanks RMQ, Doi Y, Urish KL. Elimination of Antibiotic Resistant Surgical Implant Biofilms Using an Engineered Cationic Amphipathic Peptide WLBU2. Sci Rep. 2017 Dec 22;7(1):18098. doi: 10.1038/s41598-017-17780-6. PMID: 29273750; PMCID: PMC5741726.
Deslouches B, Di YP. Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications. Oncotarget. 2017 Jul 11;8(28):46635-46651. doi: 10.18632/oncotarget.16743. PMID: 28422728; PMCID: PMC5542299.
Melvin JA, Lashua LP, Kiedrowski MR, Yang G, Deslouches B, Montelaro RC, Bomberger JM. Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection. mSphere. 2016 May 4;1(3):e00083-16. doi: 10.1128/mSphere.00083-16. PMID: 27303744; PMCID: PMC4888888.
Lashua LP, Melvin JA, Deslouches B, Pilewski JM, Montelaro RC, Bomberger JM. Engineered cationic antimicrobial peptide (eCAP) prevents Pseudomonas aeruginosa biofilm growth on airway epithelial cells. J Antimicrob Chemother. 2016 Aug;71(8):2200-7. doi: 10.1093/jac/dkw143. Epub 2016 May 26. PMID: 27231279; PMCID: PMC4954927.
Deslouches B, Hasek ML, Craigo JK, Steckbeck JD, Montelaro RC. Comparative functional properties of engineered cationic antimicrobial peptides consisting exclusively of tryptophan and either lysine or arginine. J Med Microbiol. 2016 Jun;65(6):554-565. doi: 10.1099/jmm.0.000258. Epub 2016 Apr 5. PMID: 27046192; PMCID: PMC5042116.
Abdelbaqi S, Deslouches B, Steckbeck J, Montelaro R, Reed DS. Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. J Med Microbiol. 2016 Feb;65(2):188-194. doi: 10.1099/jmm.0.000209. Epub 2015 Dec 15. PMID: 26673248.
Quinn M, Turula H, Tandon M, Deslouches B, Moghbeli T, Snyder CM. Memory T cells specific for murine cytomegalovirus re-emerge after multiple challenges and recapitulate immunity in various adoptive transfer scenarios. J Immunol. 2015 Feb 15;194(4):1726-1736. doi: 10.4049/jimmunol.1402757. Epub 2015 Jan 16. PMID: 25595792; PMCID: PMC4684174.
Deslouches B, Steckbeck JD, Craigo JK, Doi Y, Burns JL, Montelaro RC. Engineered cationic antimicrobial peptides to overcome multidrug resistance by ESKAPE pathogens. Antimicrob Agents Chemother. 2015 Feb;59(2):1329-33. doi: 10.1128/AAC.03937-14. Epub 2014 Nov 24. PMID: 25421473; PMCID: PMC4335883.
Steckbeck JD, Deslouches B, Montelaro RC. Antimicrobial peptides: new drugs for bad bugs? Expert Opin Biol Ther. 2014 Jan;14(1):11-4. doi: 10.1517/14712598.2013.844227. Epub 2013 Nov 11. PMID: 24206062; PMCID: PMC4109705.
Deslouches B, Steckbeck JD, Craigo JK, Doi Y, Mietzner TA, Montelaro RC. Rational design of engineered cationic antimicrobial peptides consisting exclusively of arginine and tryptophan, and their activity against multidrug-resistant pathogens. Antimicrob Agents Chemother. 2013 Jun;57(6):2511-21. doi: 10.1128/AAC.02218-12. Epub 2013 Mar 18. PMID: 23507278; PMCID: PMC3716171.
Neal MD, Deslouches B, Ogilvie J. The use of pre-operative imaging and intraoperative parathyroid hormone level to guide surgical management of tertiary hyperparathyroidism from X-linked hypophosphatemic rickets: a case report. Cases J. 2009 Sep 10;2:7572. doi: 10.4076/1757-1626-2-7572. PMID: 19918472; PMCID: PMC2769362.
Deslouches B, Gonzalez IA, DeAlmeida D, Islam K, Steele C, Montelaro RC, Mietzner TA. De novo-derived cationic antimicrobial peptide activity in a murine model of Pseudomonas aeruginosa bacteraemia. J Antimicrob Chemother. 2007 Sep;60(3):669-72. doi: 10.1093/jac/dkm253. Epub 2007 Jul 10. PMID: 17623696; PMCID: PMC3584960.
Deslouches B, Islam K, Craigo JK, Paranjape SM, Montelaro RC, Mietzner TA. Activity of the de novo engineered antimicrobial peptide WLBU2 against Pseudomonas aeruginosa in human serum and whole blood: implications for systemic applications. Antimicrob Agents Chemother. 2005 Aug;49(8):3208-16. doi: 10.1128/AAC.49.8.3208-3216.2005. PMID: 16048927; PMCID: PMC1196285.
Phadke SM, Deslouches B, Hileman SE, Montelaro RC, Wiesenfeld HC, Mietzner TA. Antimicrobial peptides in mucosal secretions: the importance of local secretions in mitigating infection. J Nutr. 2005 May;135(5):1289-93. doi: 10.1093/jn/135.5.1289. PMID: 15867326.
Deslouches B, Phadke SM, Lazarevic V, Cascio M, Islam K, Montelaro RC, Mietzner TA. De novo generation of cationic antimicrobial peptides: influence of length and tryptophan substitution on antimicrobial activity. Antimicrob Agents Chemother. 2005 Jan;49(1):316-22. doi: 10.1128/AAC.49.1.316-322.2005. PMID: 15616311; PMCID: PMC538858.
Phadke SM, Islam K, Deslouches B, Kapoor SA, Beer Stolz D, Watkins SC, Montelaro RC, Pilewski JM, Mietzner TA. Selective toxicity of engineered lentivirus lytic peptides in a CF airway cell model. Peptides. 2003 Aug;24(8):1099-107. doi: 10.1016/j.peptides.2003.07.001. PMID: 14612179.
Li J, Deslouches B, Cosloy SD, Russell CS. A heme-deficient strain of Escherichia coli has a three-base pair deletion in a "hotspot" in hemA. Biochim Biophys Acta. 2003 Apr 15;1626(1-3):102-5. doi: 10.1016/s0167-4781(03)00041-1. PMID: 12697336.
