IP Library › Granted Patent US 12,371,463
Granted Patent B2
US 12,371,463 · App. 17/724,927 · Granted Jul 29, 2025

Methods and compositions for treatment of antibiotic-resistant bacterial infections

Inventors: Vaughn Cooper (Wexford, PA); Alfonso Santos López (Madrid, ES)
Assignee: University of Pittsburgh—Of the Commonwealth System of Higher Education
C07K14/4723A61P31/04C12N9/1007C12N9/1048C12N9/12A61K38/00C12Y207/13003C12Y301/01061
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Quick Facts
Patent No.
US 12,371,463
App. No.
17/724,927
Granted
Jul 29, 2025
Kind
B2
Abstract

Provided in this disclosure are methods of treating a bacterial infection comprising administering a formulation comprising an antimicrobial peptide described herein when administered to a subject. Further provided herein are methods of treating a bacterial infection wherein the bacterial infection comprises a bacterium with a mutation in a gene resulting in antibiotic resistance.

Claims (29)

1. A method of treating an infection caused by a bacteria selected from Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli , the bacteria comprising a mutation in a pmrB gene, a wspF gene, or a combination thereof, or a hypermutator bacteria strain of the bacteria, in a subject, comprising:

obtaining a sample of the bacteria of the bacterial infection from the subject;

administering to the subject a formulation comprising an antimicrobial peptide or salt thereof in a therapeutically effective amount to treat the bacterial infection, wherein the antimicrobial peptide comprises SEQ ID NO: 1; and

monitoring a bacterial species obtained from the patient at one or more times after administration of the formulation for development of one or more additional mutations in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species, wherein:

one or more of the mutations is in the pmrB gene, wherein the pmrB gene encodes a histidine kinase, wherein the mutations in the pmrB gene occur in at least one codon of the pmrB gene, and wherein each of the one or more mutations occur in the histidine kinase at a position in SEQ ID NO: 29 individually selected from the group consisting of 18, 28, 44, 47, 180, 185, 248, 296, 318, 408, and equivalent positions thereof, and/or

one or more of the mutations is in the wspF gene, wherein the wspF gene encodes a protein-glutamate methylesterase, wherein the at least one mutation in the wspF gene occurs in one or more codons of the wspF gene, and wherein each of the at least one mutation occurs in the protein-glutamate methylesterase at a position in SEQ ID NO: 31, or an equivalent position thereof.

2. The method of claim 1 , further comprising before and/or during administering the formulation to the patient, determining if bacteria obtained from the patient comprises a mutation in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species.

3. The method of claim 1 , wherein if one or more mutations in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species is present in the bacteria, the subject is administered a dose of the formulation comprising the antimicrobial peptide or salt thereof in amounts exceeding a minimum inhibitory concentration (MIC) for the bacterial species.

4. The method of claim 1 , wherein if the bacterial species develops resistance to the formulation comprising the antimicrobial peptide or salt thereof, or develops one or more additional mutations in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species, discontinuing administering of the formulation to the subject.

5. The method of claim 1 , wherein one or more of the mutations is in the pmrB gene, wherein the pmrB gene encodes a histidine kinase, wherein the mutations in the pmrB gene occur in at least one codon of the pmrB gene, and wherein each of the one or more mutations occur in the histidine kinase at a position in SEQ ID NO: 29 individually selected from the group consisting of 18, 28, 44, 47, 180, 185, 248, 296, 318, 408, and equivalent positions thereof.

6. The method of claim 5 , wherein one or more of the mutations in the pmrB gene includes one or more of: V28L, L18P, A248T, L180P, V28A, D47G, F44L, L318P, V185A, L296P, and F408P.

7. The method of claim 1 , wherein one or more of the mutations is in the wspF gene, wherein the wspF gene encodes a protein-glutamate methylesterase, wherein the at least one mutation in the wspF gene occurs in one or more codons of the wspF gene, and wherein each of the at least one mutation occurs in the protein-glutamate methylesterase at a position in SEQ ID NO: 31, or an equivalent position thereof.

8. The method of claim 7 , wherein one or more of the mutations in the wspF gene includes one or more of: L20P, L51P, S159L, L199P, L222P, T274I, G280D, and G283D.

9. The method of claim 1 , wherein the bacterial species is a bacterial species with a higher mutation rate as compared to the bacterial species ancestor (non-mutator) strain.

10. The method of claim 1 , further comprising determining that the bacterial species is resistant to Polymyxin B prior to administering the formulation comprising the antimicrobial peptide or salt thereof, wherein the bacterial species further comprises a mutation in a pmrABC operon gene.

11. The method of claim 1 , wherein the formulation comprising the antimicrobial peptide or salt thereof reduces the level of bacteria that comprises the mutation in the pmrABC operon gene, relative to a wildtype pmrABC operon gene present in a wild type bacteria species, to an extent comparable to a reduction of a level of the bacteria that comprises the wildtype pmrABC operon gene by the formulation comprising the antimicrobial peptide or salt thereof, as determined by an in vitro assay.

12. A method of treating an infection caused by Pseudomonas aeruginosa , the bacteria comprising a mutation in a pmrB gene, a wspF gene, an orfN gene, or a combination thereof, or a hypermutator bacteria strain of the bacteria, in a subject, comprising:

obtaining a sample of the bacteria of the bacterial infection from the subject;

administering to the subject a formulation comprising an antimicrobial peptide or salt thereof in a therapeutically effective amount to treat the bacterial infection, wherein the antimicrobial peptide comprises SEQ ID NO: 1; and

monitoring a bacterial species obtained from the patient at one or more times after administration of the formulation for development of one or more additional mutations in at least one gene affecting an outer membrane of the bacteria species and/or aggregation of the bacteria species, wherein:

one or more of the mutations is in the pmrB gene, wherein the pmrB gene encodes a histidine kinase, wherein the mutations in the pmrB gene occur in at least one codon of the pmrB gene, and wherein each of the one or more mutations occur in the histidine kinase at a position in SEQ ID NO: 29 individually selected from the group consisting of 18, 28, 44, 47, 180, 185, 248, 296, 318, and 408,

one or more of the mutations is in the orfN gene, wherein the orfN gene encodes a putative group 4 glycosyl transferase, wherein the at least one mutation in the orfN gene is in at least one codon of the orfN gene, and wherein the at least one mutation occurs in the putative group 4 glycosyl transferase at position 10 in SEQ ID NO: 30, and/or

one or more of the mutations is in the wspF gene, wherein the wspF gene encodes a protein-glutamate methylesterase, wherein the at least one mutation in the wspF gene occurs in one or more codons of the wspF gene, and wherein each of the at least one mutation occurs in the protein-glutamate methylesterase at a position in SEQ ID NO: 31.

13. The method of claim 12 , wherein one or more of the mutations is in the pmrB gene, wherein the pmrB gene encodes a histidine kinase, wherein the mutations in the pmrB gene occur in at least one codon of the pmrB gene, and wherein each of the one or more mutations occur in the histidine kinase at a position in SEQ ID NO: 29 individually selected from the group consisting of 18, 28, 44, 47, 180, 185, 248, 296, 318, and 408.

14. The method of claim 12 , wherein one or more of the mutations in the pmrB gene includes one or more of: V28L, L18P, A248T, L180P, V28A, D47G, F44L, L318P, V185A, L296P, and F408P.

15. The method of claim 12 , wherein one or more of the mutations is in the wspF gene, wherein the wspF gene encodes a protein-glutamate methylesterase, wherein the at least one mutation in the wspF gene occurs in one or more codons of the wspF gene, and wherein each of the at least one mutation occurs in the protein-glutamate methylesterase at a position in SEQ ID NO: 31.

16. The method of claim 15 , wherein one or more of the mutations in the wspF gene includes one or more of: L20P, L51P, S159L, L199P, L222P, T274I, G280D, and G283D.

17. The method of claim 12 , wherein one or more of the mutations is in the orfN gene, wherein the orfN gene encodes a putative group 4 glycosyl transferase, wherein the at least one mutation in the orfN gene is in at least one codon of the orfN gene, and wherein the at least one mutation occurs in the putative group 4 glycosyl transferase at position 10 in SEQ ID NO: 30.

18. The method of claim 12 , wherein the mutation in the orfN gene results in at least two different changes in the glycosyl transferase, wherein one of the at least two mutations comprise (10) G to (9) G.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 4, 2024
From: COOPER, VAUGHN; SANTOS LÓPEZ, ALFONSO
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 069481/0535 →
Continuity (3)
Provisional Application 63287686 · Dec 9, 2021
Provisional Application 63177046 · Apr 20, 2021
Related Publication 20220332777A1 · Oct 20, 2022
References Cited (225)
US 5504190A · Houghten et al. · 1996 [cited by applicant]
US 5714577A · Montelaro et al. · 1998 [cited by applicant]
US 5945507A · Montelaro et al. · 1999 [cited by applicant]
US 5981698A · Brittain · 1999 [cited by applicant]
US 6835713B2 · Montelaro et al. · 2004 [cited by applicant]
US 6887847B2 · Montelaro et al. · 2005 [cited by applicant]
US 6974701B2 · Bouboulis · 2005 [cited by applicant]
US 8071540B2 · Montelaro et al. · 2011 [cited by applicant]
US 8357394B2 · Flanner et al. · 2013 [cited by applicant]
US 20030036627A1 · Montelaro et al. · 2003 [cited by applicant]
US 20040043041A1 · Baker, Jr. et al. · 2004 [cited by applicant]
US 20050025761A1 · Thorpe et al. · 2005 [cited by applicant]
US 20050282239A1 · Allbritton et al. · 2005 [cited by applicant]
US 20070225213A1 · Kosak · 2007 [cited by applicant]
US 20090053278A1 · Fatora et al. · 2009 [cited by applicant]
US 20090099533A1 · Montelaro et al. · 2009 [cited by applicant]
US 20090198200A1 · Tumey et al. · 2009 [cited by applicant]
US 20100210506A1 · Quay et al. · 2010 [cited by applicant]
US 20130261534A1 · Niezgoda et al. · 2013 [cited by applicant]
US 20150118183A1 · Baumhof · 2015 [cited by applicant]
US 20200071361A1 · Steckbeck · 2020 [cited by applicant]
US 20200121495A1 · Nelson et al. · 2020 [cited by applicant]
US 20200277334A1 · Steckbeck · 2020 [cited by applicant]
US 20220054589A1 · Urish et al. · 2022 [cited by applicant]
EP 0273716B1 · 1988 [cited by applicant]
WO WO02066608A2 · 2002 [cited by examiner]
WO 03103718A2 · 2003 [cited by applicant]
WO 2008070083A2 · 2008 [cited by applicant]
WO 2010112848A2 · 2010 [cited by applicant]
WO 2013169264A1 · 2013 [cited by applicant]
WO 2018125746A1 · 2018 [cited by applicant]
WO 2018160997A1 · 2018 [cited by applicant]
WO 2018187617A1 · 2018 [cited by applicant]
WO 2019178274A1 · 2019 [cited by applicant]
WO 2021130390A1 · 2021 [cited by applicant]
Santos-Lopez et al. (Experimental evolution to identify undescribed mechanisms 1 of resistance to a novel cationic, bioRxiv 2020.12.16.423161) (Year: 2020). [cited by examiner]
Sanz-Garcia et al. (Front Genet. Oct. 18, 2018;9:451) (Year: 2018). [cited by examiner]
Moskowitz et al. (Antimicrob Agents Chemother. Feb. 2012; 56(2): 1019-1030) (Year: 2012). [cited by examiner]
Swedan et al., Synergism of cationic antimicrobial peptide WLBU2 with antibacterial agents against biofilms of multi-drug resistant Acinetobacter baumannii and Klebsiella pneumoniae, Infection and Drug Resistance, 2019,… [cited by applicant]
Tam et al., Disulfide Bond Formation in Peptides by Dimethyl Sulfoxide. Scope and Applications, J. Am. Chem. Soc., 1991, pp. 6657-6662, vol. 113, American Chemical Society. [cited by applicant]
Tande et al., Clinical Presentation, Risk Factors, and Outcomes of Hematogenous Prosthetic Joint Infection in Patients with [cited by applicant]
Tande et al., Prosthetic Joint Infection, Clinical Microbiology Reviews, 2014, pp. 302-345, vol. 27, No. 2, American Society for Microbiology. [cited by applicant]
Tencza et al., Lentivirus-derived antimicrobial peptides: increased potency by sequence engineering and dimerization, Journal of Antimicrobial Chemotherapy, 1999, pp. 33-41, vol. 44, The British Society for Antimicrobia… [cited by applicant]
Tencza et al., Calmodulin-Binding Function of LLP Segments from the HIV Type 1 Transmembrane Protein Is Conserved among Natural Sequence Variants, Aids Research and Human Retroviruses, 1997, pp. 263-269, vol. 13, No. 3,… [cited by applicant]
Tencza et al., Novel Antimicrobial Peptides Derived from Human Immunodeficiency Virus Type 1 and Other Lentivirus Transmembrane Proteins, Antimicrobial Agents and Chemotherapy, 1997, pp. 2394-2398, vol. 41, No. 11, Amer… [cited by applicant]
Tencza et al., Effect of Amino Acid Substitutions on Calmodulin Binding and Cytolytic Properties of the LLP-1 Peptide Segment of Human Immunodeficiency Virus Type 1 Transmembrane Protein, Journal of Virology, 1995, pp. … [cited by applicant]
Toprak et al., Evolutionary paths to antibiotic resistance under dynamically sustained drug selection, Nature Genetics, 2012, pp. 101-106, vol. 44, No. 1, Nature America, Inc. [cited by applicant]
Trampari et al., Antibiotics select for novel pathways of resistance in biofilms, bioRxiv, 2019, pp. 1-67. [cited by applicant]
Urish et al., Antibiotic-tolerant [cited by applicant]
Venable et al., Theoretically Determined Three-Dimensional Structures for Amphipathic Segments of the HIV-1 gp41 Envelope Protein, AIDS Research and Human Retroviruses, 1989, pp. 7-22, vol. 5, No. 1, Mary Ann Liebert, I… [cited by applicant]
Vogwill et al., Testing the Role of Genetic Background in Parallel Evolution Using the Comparative Experimental Evolution of Antibiotic Resistance, Mol. Biol. Evol., 2014, pp. 3314-3323. [cited by applicant]
Von Eiff et al., Infections Associated with Medical Devices: Pathogenesis, Management and Prophylaxis, Drugs, 2005, pp. 179-214, vol. 65, Adis Data Information BV. [cited by applicant]
Wachinger et al., Influence of amphipathic peptides on the HIV-1 production in persistently infected T lymphoma cells, 1992, pp. 235-241, vol. 309, No. 3, Elsevier Science Publishers B.V. [cited by applicant]
Wachinger et al., Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression, Journal of General Virology, 1998, p. 731-740, vol. 79, SGM. [cited by applicant]
Walkenhorst et al., pH Dependence of Microbe Sterilization by Cationic Antimicrobial Peptides, Antimicrobial Agents and Chemotherapy, 2013, pp. 3312-3320, vol. 57, No. 7, American Society for Microbiology. [cited by applicant]
Ward et al., Inhibition of protein kinase C by a synthetic peptide corresponding to cytoplasmic domain residues 828-848 of the human immunodeficiency virus type 1 envelope glycoprotein, Cancer Letters, 1995, pp. 37-40, … [cited by applicant]
Wheeler et al., Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domain, Biochemical and Biophysical Research Communications, 2003, pp. 54-59, vol. 301, Elsevier Science (USA). [cited by applicant]
Wild et al., A synthetic peptide inhibitor of human immunodeficiency virus replication: Correlation between solution structure and viral inhibition, Proc. Natl. Acad. Sci. USA, 1992, pp. 10537-10541, vol. 89, Medical Sc… [cited by applicant]
Wu et al., Adsorption, structural alteration and elution of peptides at pendant PEO layers, Colloids Surf B Biointerfaces, 2013, pp. 1-18, vol. 112, Elsevier B.V. [cited by applicant]
Wu et al., Sequential and competitive adsorption of peptides at pendant PEO layers, Colloids Surf B Biointerfaces, 2015, pp. 69-76, vol. 130, Elsevier B.V. [cited by applicant]
Wu et al., Concentration effects on peptide elution from pendant PEO layers, Colloids Surf B Biointerfaces, 2014, pp. 210-217, vol. 118, Elsevier B.V. [cited by applicant]
Yang et al., Antimicrobial peptide-modified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy, Photochem. Photobiol. Sci., 2011, pp. 1593-1601, vol. 10, The Royal Society … [cited by applicant]
Yasin et al., Evaluation of the Inactivation of Infectious Herpes Simplex Virus by Host-Defense Peptides, Eur J Clin Micobiol Infect Dis, 2000, pp. 187-194, vol. 19, Springer-Verlag. [cited by applicant]
Yuan et al., Characterization of the Calmodulin Binding Domain of SIV Transmembrane Glycoprotein by NMR and CD Spectroscopy, Biochemistry, 1995, pp. 10690-10696, vol. 34, American Chemical Society. [cited by applicant]
Zabner et al., Adenovirus-Mediated Gene Transfer to Ciliated Airway Epithelia Requires Prolonged Incubation Time, Journal of Virology, 1996, pp. 6994-7003, vol. 70, No. 10, American Society for Microbiology. [cited by applicant]
Zanetti et al., Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain, FEBS Letters, 1995, pp. 1-5, vol. 374, Federation of European Biochemical Societies. [cited by applicant]
Zasloff, Antimicrobial peptides of multicellular organisms, Nature, 2002, pp. 389-395, vol. 415, Macmillan Magazines Ltd. [cited by applicant]
Zhang et al., Interactions of Bacterial Cationic Peptide Antibiotics with Outer and Cytoplasmic Membranes of Pseudomonas aeruginosa, Antimicrobial Agents and Chemotherapy, 2000, pp. 3317-3321, vol. 44, No. 12, American … [cited by applicant]
Zhang et al., Amphipathic domains in the C terminus of the transmembrane protein (gp41) permeabilize HIV-1 virions: A molecular mechanism underlying natural endogenous reverse transcription, Proc. Natl. Acad. Sci. USA, … [cited by applicant]
Ziegler et al., The Cationic Cell-Penetrating Peptide CPP(TAT) Derived from the HIV-1 Protein TAT Is Rapidly Transported into Living Fibroblasts: Optical, Biophysical, and Metabolic Evidence, Biochemistry, 2005, pp. 138… [cited by applicant]
Zimmerli et al., Prosthetic-Joint Infections, The New England Journal of Medicine, 2004, pp. 1645-1654, vol. 351, Massachusetts Medical Society. [cited by applicant]
Zmistowski et al., Periprosthetic Joint Infection Increases the Risk of One-Year Mortality, J Bone Joint Surg Am, 2013, pp. 2177-2184, vol. 95, The Journal of Bone and Joint Surgery. [cited by applicant]
Abdelbaqi et al., Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei, Journal of Medical Microbiology, 2016, pp… [cited by applicant]
Ahmed et al., Evolution of Antibiotic Resistance in Biofilm and Planktonic Pseudomonas aeruginosa Populations Exposed to Subinhibitory Levels of Ciprofloxacin, Antimicrobial Agents and Chemotherapy, 2018, pp. 1-12, vol.… [cited by applicant]
Arroyo et al., Membrane Permeabilization by Different Regions of the Human Immunodeficiency Virus Type 1 Transmembrane Glycoprotein gp41, Journal of Virology, 1995, pp. 4095-4102, vol. 69, No. 7, American Society for Mi… [cited by applicant]
Bailey et al., The Effect of Selection Environment on the Probability of Parallel Evolution, Mol. Biol. Evol. 2015, pp. 1436-1448, vol. 32. [cited by applicant]
Barbosa et al., Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa, eLife, 2019, pp. 1-22. [cited by applicant]
Barrick et al., Identifying structural variation in haploid microbial genomes from short-read resequencing data using preseq, BMC Genomics, 2014, pp. 1-17, vol. 15. [cited by applicant]
Baym et al., Inexpensive Multiplexed Library Preparation for Megabase-Sized Genomes, PLOS ONE, 2015, pp. 1-15, vol. 10, No. 5. [cited by applicant]
Beary et al., Interruption of T-cell signal transduction by lentivirus lytic peptides from HIV-1 transmembrane protein, J. Peptide Res., 1998, pp. 75-79, vol. 51, Munksgaard. [cited by applicant]
Bell et al., The Search for ‘Evolution-Proof’ Antibiotics, Trends in Microbiology, 2018, pp. 471-483, vol. 26, No. 6, Elsevier Ltd. [cited by applicant]
Berge et al., Pharmaceutical Salts, Journal of Pharmaceutical Sciences, 1977, pp. 1-19, vol. 66, No. 1. [cited by applicant]
Beumer et al., Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice, Current Reviews in Clinical and Experimental Pharmacology, 2021, pp. 2… [cited by applicant]
Blondelle et al., Design of Model Amphipathic Peptides Having Potent Antimicrobial Activities, Biochemistry, 1992, pp. 12688-12694, vol. 31. [cited by applicant]
Bolger et al., Trimmomatic: a flexible trimmer for Illumina sequence data, Bioinformatics, 2014, pp. 2114-2120, vol. 30, No. 15, Oxford University Press. [cited by applicant]
Brockhurst et al., Assessing evolutionary risks of resistance for new antimicrobial therapies, Nature Ecology & Evolution, 2019, pp. 515-517, vol. 3. [cited by applicant]
Brown et al., Dilute Betadine Lavage Before Closure for the Prevention of Acute Postoperative Deep Periprosthetic Joint Infection, The Journal of Arthroplasty, 2012, pp. 27-30, vol. 27, No. 1, Elsevier Inc. [cited by applicant]
Brutlag et al., Improved sensitivity of biological sequence database searches, Cabios, 1990, pp. 237-245, vol. 6, No. 3, Oxford University Press. [cited by applicant]
Bucki et al., Resistance of the antibacterial agent ceragenin CSA-13 to inactivation by DNA or F-actin and its activity in cystic fibrosis sputum, Journal of Antimicrobial Chemotherapy, 2007, pp. 1-12. [cited by applicant]
Bucki et al., Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13, Journal of Antimicrobial Chemotherapy, 2008, pp. 329-335, vol. 62, Oxford Unive… [cited by applicant]
Burton et al., Antibiofilm Activity of GlmU Enzyme Inhibitors against Catheter-Associated Uropathogens, Antimicrobial Agents and Chemotherapy, 2006, pp. 1835-1840, vol. 50, No. 5, American Society for Microbiology. [cited by applicant]
Byfield et al., Cathelicidin LL-37 Increases Lung Epithelial Cell Stiffness, Decreases Transepithelial Permeability, and Prevents Epithelial Invasion by Pseudomonas aeruginosa, The Journal of Immunology, 2011, pp. 6402-… [cited by applicant]
Cannatelli et al., An allelic variant of the PmrB sensor kinase reponsible for colistin resistance in an [cited by applicant]
Caron et al., Intracellular Delivery of a Tat-eGFP Fusion Protein into Muscle Cells, Molecular Therapy, 2001, pp. 310-318, vol. 3, No. 3, The American Society of Gene Therapy. [cited by applicant]
Chan et al., Selective Permeabilization of Gram-Negative Bacterial Membranes Using Multivalent Peptide Constructs for Antibiotic Sensitization, ACS Infectious Diseases, 2021, pp. 721-732, vol. 7, American Chemical Socie… [cited by applicant]
Chen et al., Enhanced efficacy of the engineered antimicrobial peptide WLBU2 via direct airway delivery in a murine model of Pseudomonas aeruginosa pneumonia, Clinical Microbiology and Infection, 2018, pp. 547e1-547e8, … [cited by applicant]
Chernomordik et al., An amphipathic Peptide from the C-Terminal Region of the Human Immunodeficiency Virus Envelope Glycoprotein Causes Pore Formation in Membranes, Journal of Virology, 1994, pp. 7115-7123, vol. 68, No.… [cited by applicant]
Chou et al., Prediction of the Secondary Structure of Proteins from their amino acid sequence, Adv Enzymol Relat Areas Mol Biol., 1978, pp. 45-148, vol. 47. [cited by applicant]
Chou et al., Prediction of Protein Conformation, Biochemistry, 1974, pp. 222-245, vol. 13, No. 2. [cited by applicant]
Cirioni et al., Pre-treatment of central venous catheters with the cathelicidin BMAP-28 enhances the efficacy of antistaphylococcal agents in the treatment of experimental catheter-related infection, Peptides, 2006, pp.… [cited by applicant]
Comardelle et al., A Synthetic Peptide Corresponding to the Carboxy Terminus of Human Immunodeficiency Virus Type 1 Transmembrane Glycoprotein Induces Alterations in the lonic Permeability of Xenopus laevis Oocytes, AID… [cited by applicant]
Cooper, Experimental Evolution as a High-Throughput Screen for Genetic Adaptations, mSphere, 2018, pp. 1-7, vol. 3, issue 3. [cited by applicant]
Deatherage et al., Identification of mutations in laboratory evolved microbes from next-generation sequencing data using breseq, Methods Mol Biol., 2014, pp. 165-188, vol. 1151. [cited by applicant]
Deslouches et al., De Novo Generation of Cationic Antimicrobial Peptides: Influence of Length and Tryptophan Substitution on Antimicrobial Activity, Antimicrobial Agents and Chemotherapy, 2005, pp. 316-322, vol. 49, No.… [cited by applicant]
Deslouches et al., Comparative functional properties of engineered cationic antimicrobial peptides consisting exclusively of tryptophan and either lysine or arginine, Journal of Medical Microbiology, 2016, pp. 554-565, … [cited by applicant]
Deslouches et al., De novo-derived cationic antimicrobial peptide activity in a murine model of Pseudomonas aeruginosa bacteraemia, Journal of Antimicrobial Chemotherapy, 2007, pp. 669-672, vol. 60, Oxford University Pr… [cited by applicant]
Deslouches et al., Engineered Cationic Antimicrobial Peptides to Overcome Multidrug Resistance by ESKAPE Pathogens, Antimicrobial Agents and Chemotherapy, 2015, pp. 1329-1333, vol. 59, No. 2, American Society for Microb… [cited by applicant]
Deslouches et al., Rational Design of Engineered Cationic Antimicrobial Peptides Consisting Exclusively of Arginine and Tryptophan, and Their Activity against Multidrug-Resistant Pathogens, Antimicrobial Agents and Chem… [cited by applicant]
Deslouches et al., Activity of the De Novo Engineered Antimicrobial Peptide WLBU2 against Pseudomonas aeruginosa in Human Serum and Whole Blood: Implications for Systemic Applications, Antimicrobial Agents and Chemother… [cited by applicant]
De Visser et al., Diminishing Returns from Mutation Supply Rate in Asexual Populations, Science, 1999, pp. 404-407, vol. 283. [cited by applicant]
Di et al., Enhanced therapeutic index of an antimicrobial peptide in mice by increasing safety and activity against multidrug-resistant bacteria, Science Advances, 2020, pp. 1-10, vol. 6. [cited by applicant]
Dietz et al., Delivery of bioactive molecules into the cell: the Trojan horse approach, Mol. Cell. Neurosci., 2004, pp. 35-131, vol. 27, Elsevier Inc. [cited by applicant]
Dillon et al., Genome-Wide Biases in the Rate and Molecular Spectrum of Spontaneous Mutations in Vibrio cholerae and Vibrio fischeri, Mol. Biol. Evol., 2016, pp. 93-109, vol. 34, Oxford University Press. [cited by applicant]
Donlan et al., Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms, Clinical Microbiology Reviews, 2002, pp. 167-193, vol. 15, No. 2, American Society for Microbiology. [cited by applicant]
Eisenberg et al., Analysis of Membrane and Surface Protein Sequences with the Hydrophobic Moment Plot, J. Mol. Biol., 1984, pp. 125-142, vol. 179, Academic Press Inc (London) Ltd. [cited by applicant]
Eisenberg et al., The hydrophobic moment detects periodicity in protein hydrophobicity, Proc. Natl. Acad. Sci., 1984, pp. 140-144, vol. 81. [cited by applicant]
Eisenberg et al., The Most Highly Amphiphilic a-Helices Include Two Amino Acid Segments in Human Immunodeficiency Virus Glycoprotein 41, Biopolymers, 1990, pp. 171-177, vol. 29, John Wiley & Sons, Inc. [cited by applicant]
El-Ghannam et al., Nanoporous Delivery System to Treat Osteomyelitis and Regenerate Bone: Gentamicin Release Kinetics and Bactericidal Effect, J Biomed Mater Res Part B: Appl Biomater, 2005, pp. 277-284, vol. 73B, Wiley… [cited by applicant]
Ellman, Tissue Sulfydryl Groups, Archives of Biochemistry and Biophysics, 1959, pp. 70-77, vol. 82. [cited by applicant]
Redefining STEM Learning, EvolvingSTEM, 2020, https://web.archive.org/web/20201125222559/https://evolvingstem.org/. [cited by applicant]
Falagas et al., Rifampicin-impregnated central venous catheters: a meta-analysis of randomized controlled trials, Journal of Antimicrobial Chemotherapy, 2007, pp. 359-369, vol. 59. [cited by applicant]
Fernandez et al., Characterization of the Polymyxin B Resistome of Pseudomonas aeruginosa, Antimicrobial Agents and Chemotherapy, 2013, pp. 110-119, vol. 57. [cited by applicant]
Maltas et al., Pervasive and diverse collateral sensitivity profiles inform optimal strategies to limit antibiotic resistance, PLOS Biology, 2019, pp. 1-34, vol. 17, No. 10. [cited by applicant]
Mandell et al., Elimination of Antibiotic Resistant Surgical Implant Biofilms Using an Engineered Cationic Amphipathic Peptide WLBU2, Scientific Reports, 2017, pp. 1-9, vol. 7. [cited by applicant]
Mandell et al., Direct antimicrobial activity of cationic amhipathic peptide WLBU2 against [cited by applicant]
Mcclanahan et al., Bioactivity of WLBU2 peptide antibiotic in combination with bioerodible polymer, Int J Antimicrob Agents, 2011, pp. 530-533, vol. 38, Elsevier B.v. and the International Society of Chemotherapy. [cited by applicant]
Mehta et al., Using experimental evolution to identify druggable targets that could inhibit the evolution of antimicrobial resistance, J Antibiot (Tokyo), pp. 279-286, vol. 71. [cited by applicant]
Melvin et al., Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection, mSphere, 2016, pp. 1-11, vol. 1, issue 3. [cited by applicant]
Mena et al., Genetic Adaptation of Pseudomonas aeruginosa to the Airways of Cystic Fibrosis Patients Is Catalyzed by Hypermutation, Journal of Bacteriology, 2008, pp. 7910-7917, vol. 190, No. 24, American Society for Mi… [cited by applicant]
Merrifield et al., Design and synthesis of antimicrobial peptides, Antimicrobial peptides, 1994, pp. 5-26, Wiley, Chichester. [cited by applicant]
Mi et al., Characterization of a Class of Cationic Peptides Able to Facilitate Efficient Protein Transduction in Vitro and in Vivo, Molecular Therapy, 2000, pp. 339-347, vol. 2, No. 4, The American Society of Gene Thera… [cited by applicant]
Miller et al., Alterations in Cell Membrane Permeability by the Lentivirus Lytic Peptide (LLP-1) of HIV-1 Transmembrane Protein, Virology, 1993, pp. 89-100, vol. 196, Academic Press, Inc. [cited by applicant]
Miller et al., A Structural Correlation Between Lentivirus Transmembrane Proteins and Natural Cytolytic Peptides, AIDS Research and Human Retroviruses, 1991, pp. 511-519, vol. 7, No. 6, Mary Ann Liebert, Inc., Publisher… [cited by applicant]
Miller et al., Identification of a Calmodulin-Binding and Inhibitory Peptide Domain in the HIV-1 Transmembrane Glycoprotein, Aids Research and Human Retroviruses, 1993, 1057-1066, vol. 9, No. 11, Mary Ann Liebert, Inc.,… [cited by applicant]
Moore et al., Preliminary Experimental Anticancer Activity of Cecropins, Peptide Research, 1994, pp. 265-269, vol. 7, No. 5. [cited by applicant]
Moran et al., The diagnosis and management of prosthetic joint infections, J Antimicrob Chemother, 2010, pp. ii45-ii54, vol. 65, Oxford University Press. [cited by applicant]
Morris et al., A peptide carrier for the delivery of biologically active proteins into mammalian cells, Nature Biotechnology, 2001, pp. 1173-1176, vol. 19, Nature Publishing Group. [cited by applicant]
Moskowitz et al., PmrB Mutations Promote Polymyxin Resistance of Pseudomonas aeruginosa Isolated from Colistin-Treated Cystic Fibrosis Patients, Antimicrobial Agents and Chemotherapy, 2011, pp. 1019-1030, American Socie… [cited by applicant]
Novak et al., Efficacy of the De Novo-Derived Antimicrobial Peptide WLBU2 against Oral Bacteria, Antimicrobial Agents and Chemotherapy, 2007, pp. 1837-1839, vol. 51, No. 5, American Society for Microbiology. [cited by applicant]
Oliver et al., High Frequency of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Lung Infection, Science, 2000, pp. 1251-1253, vol. 288. [cited by applicant]
Palace et al., Determination of amino acids in diverse polymeric matrices using HPLC with emphasis on agars and agaroses, Biochimica et Biophysica Acta, 1999, pp. 509-518, vol. 1472, Elsevier Science B.V. [cited by applicant]
Papkou et al., Efflux pump activity potentiates the evolution of antibiotic resistance across [cited by applicant]
Paranjape et al., Modulation of proinflammatory activity by the engineered cationic antimicrobial peptide WLBU-2, F1000Research, 2013, pp. 1-9. [cited by applicant]
Pearson et al., Method for Reliable Determination of Minimal Lethal Antibiotic Concentrations, Antimicrobial Agents and Chemotherapy, 1980, pp. 699-708, vol. 18, No. 5. [cited by applicant]
Perron et al., Experimental evolution of resistance to an antimicrobial peptide, Proc. R. Soc. B, 2006, pp. 251-256, vol. 273, The Royal Society. [cited by applicant]
Pettit et al., Application of a high throughput Alamar blue biofilm susceptibility assay to [cited by applicant]
Phadke et al., Selective toxicity of engineered lentivirus lytic peptides in a CF airway cell model, Peptides, 2003, pp. 1099-1107, vol. 24, Elsevier Inc. [cited by applicant]
Phadke et al., Antimicrobial Peptides in Mucosal Secretions: The Importance of Local Secretions in Mitigating Infection, Symposium: Innate Immunity and Human Milk, 2005, American Society for Nutritional Sciences. [cited by applicant]
Pulido et al., Periprosthetic Joint Infection, Clin Orthop Relat Res, 2008, pp. 1710-1715, vol. 466, The Association of Bone and Joint Surgeons. [cited by applicant]
Raman et al., Enhanced capture of bacteria and endotoxin by antimicrobial WLBU2 peptide tethered on polyethylene oxide spaces, Biointerphases, 2017, pp. 1-11, vol. 12, American Vacuum Society. [cited by applicant]
Remington: The Science and Practice of Pharmacy, Chs. 37, 41-45, and 47, 21st Edition, Lippincott Williams & Wilkins. [cited by applicant]
Ribeiro et al., Heme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic beta-cells, Biochemical and Biophysical Research Communications, 2003, pp. 876-881, vol. 305, Elsevier Science (USA). [cited by applicant]
Robinson et al., Integrative Genomics Viewer, Nat Biotechnol, 2011, pp. 24-26, vol. 29. [cited by applicant]
Robinson Jr et al., Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils, Journal of Leukocyte Biology, 1998, pp. 94-100, vol. 63. [cited by applicant]
Rocchetta et al., Genetics of O-Antigen Biosynthesis in Pseudomonas aeruginosa, Microbiology and Molecular Biology Reviews, 1999, pp. 523-553, vol. 63, No. 3, American Society for Microbiology. [cited by applicant]
Ruder et al., Treatment of Periprosthetic Joint Infection Using Antimicrobials: Dilute Povidone-Iodine Lavage, J. Bone Joint Infect., 2017, pp. 10-14, vol. 2, Ivyspring International Publisher. [cited by applicant]
Rushlow et al., Lentivirus Genomic Organization: The Complete Nucleotide Sequence of the env Gene Region of Equine Infectious Anemia Virus, Virology, 1986, pp. 309-321, vol. 155, American Press. [cited by applicant]
Ryder et al., Binding Interactions of Bacterial Lipopolysaccharide and the Cationic Amphiphilic Peptides Polymyxin B and WLBU2, Colloids Surf B Biointerfaces, 2014, pp. 81-87, vol. 120, Elsevier B.V. [cited by applicant]
Santajit et al., Mechanisms of Antimicrobial Resistance in ESKAPE pathogens, BioMed Research International, 2016, pp. 1-8, Hindawi Publishing Corporation. [cited by applicant]
Santos-Lopez et al., Experimental evolution to identify undescribed mechanisms of resistance to a novel cationic peptide antibiotic, bioRxiv, 2020, pp. 1-21. [cited by applicant]
Santos-Lopez et al., Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle, eLife, 2019, pp. 1-23. [cited by applicant]
Santos-Lopez et al., Experimental evolution to identify undescribed mechanisms of resistance to a novel cationic peptide antibiotic, bioRxiv, 2021, pp. 1-26. [cited by applicant]
Sarin et al., Quantitative Monitoring of Solid-Phase Peptide Synthesis by the Ninhydrin Reaction, Analytical Biochemistry, 1981, pp. 147-157, vol. 117, Academic Press, Inc. [cited by applicant]
Scott et al. Biological Properties of Structurally Related alpha-Helical Cationic Antimicrobial Peptides, Infection and Immunity, 1999, pp. 2005-2009, vol. 67, No. 4, American Society for Microbiology. [cited by applicant]
Scribner et al., Parallel Evolution of Tobramycin Resistance across Species and Environments, mBio, 2020, pp. 1-17, vol. 11, issue 3. [cited by applicant]
Shaver et al., Fitness Evolution and the Rise of Mutator Alleles in Experimental [cited by applicant]
Shen et al., Evaluation of Peptide-Mediated Transduction in Human CD34+ Cells, Human Gene Therapy, 2004, pp. 415-419, vol. 15, Mary Ann Liebert, Inc. [cited by applicant]
Skinner et al., Evaluation of WLBU2 Peptide and 3-O-Octyl-sn-Glycerol Lipid as Active Ingredients for a Topical Microbicide Formulation Targeting Chlamydia trachomatis, Antimicrobial Agents and Chemotherapy, 2010, pp. 6… [cited by applicant]
Spohn et al., Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance, Nature Communications, 2019, pp. 1-13. [cited by applicant]
Srinivas et al., Calmodulin Antagonists Inhibit Human Immunodeficiency Virus-Induced Cell Fusion but Not Virus Replication, AIDS Research and Human Retroviruses, 1994, pp. 1489-1496, vol. 10, No. 11. [cited by applicant]
Srinivas et al., Cytosolic Domain of the Human Immunodeficiency Virus Envelope Glycoproteins Binds to Calmodulin and Inhibits Calmodulin-regulated Proteins, The Journal of Biological Chemistry, 1993, pp. 22895-22899, vo… [cited by applicant]
Starkey et al., Pseudomonas aeruginosa Rugose Small-Colony Variants Have Adaptations That Likely Promote Persistence in the Cystic Fibrosis Lung, Journal of Bacteriology, 2009, pp. 3492-3503, vol. 191, No. 11, American … [cited by applicant]
File, Overview of Resistance in the 1990s, Chest, 1999, pp. 3S-8S, vol. 115, American College of Chest Physicians. [cited by applicant]
Flynn et al., Evolution of Ecological Diversity in Biofilms of Pseudomonas aeruginosa by Altered Cyclic Diguanylate Signaling, Journal of Bacteriology, 2016, pp. 2608-2618, vol. 198, No. 19. [cited by applicant]
Fontenot et al., A Survey of Potential Problems and Quality Control in Peptide Synthesis by the Fluorenylmethoxycarbonyl Procedure, Peptide Research, 1991, pp. 19-25, vol. 4, No. 1. [cited by applicant]
Friedrich et al., Salt-Resistant Alpha-Helical Cationic Antimicrobial Peptides, Antimicrobial Agents and Chemotherapy, 1999, pp. 1542-1548, vol. 43, No. 7, American Society for Microbiology. [cited by applicant]
Frisch et al., Intraoperative chlorhexidine irrigation to prevent infection in total hip and knee arthroplasty, Arthroplasty Today, 2017, pp. 294-297, vol. 3, Elsevier Inc. [cited by applicant]
Fujii et al., A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41, Protein Science, 1992, pp. 1454-1464, The Protein Society. [cited by applicant]
Fux et al., Survival strategies of infectious biofilms, Trends in Microbiology, 2005, pp. 34-40, vol. 13, No. 1, Elsevier td. [cited by applicant]
Ganz et al., Antimicrobial peptides of leukocytes, Current Opinion in Hematology 1997, pp. 53-58, vol. 4, Rapid Science Publishers. [cited by applicant]
Garnier et al., Analysis of the Accuracy and Implications of Simple Methods for Predicting the Secondary Structure of Globular Proteins, J. Mol. Biol., 1978, pp. 97-120, vol. 120, Academic Press Inc. (London) Ltd. [cited by applicant]
Gawrisch et al., Interaction of Peptide Fragment 828-848 of the Envelope Glycoprotein of Human Immunodeficiency Virus Type I with Lipid Bilayers, Biochemistry, 1993, pp. 3112-3118, vol. 32, American Chemical Society. [cited by applicant]
George et al., Use of Chlorhexidine Preparations in Total Joint Arthroplasty, J. Bone Joint Infect., 2017, pp. 15-22, vol. 2, Ivyspring International Publisher. [cited by applicant]
Gifford et al., Mutators drive evolution of multi-resistance to antibiotics, bioRxiv, 2021, pp. 1-36. [cited by applicant]
Gloag et al., Pseudomonas aeruginosa Interstrain Dynamics and Selection of Hyperbiofilm Mutatnts during a Chronic Infection, mBio (ASM Journals), 2019, pp. 1-16, vol. 10, issue 4. [cited by applicant]
Golbek et al., Identifying the selectivity of antimicrobial peptides to cell membranes by sum frequency generation spectroscopy, Biointerphases, 2017, pp. 1-10, vol. 12, American Vacuum Society. [cited by applicant]
Guelen et al., TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells, Oncogene, 2004, pp. 1153-1165, vol. 23, Nature Publishing Group. [cited by applicant]
Gullberg et al., Selection of Resistant Bacteria at Very Low Antibiotic Concentrations, PLOS Pathogens, 2011, pp. 1-9, vol. 7, issue 7. [cited by applicant]
Ha et al., c-di-GMP and its effects on biofilm formation and dispersion: a Pseudomonas aeruginosa review, Microbiol Spectr., 2015, pp. 1-20, vol. 3, issue 2. [cited by applicant]
Habermann, Bee and Wasp Venoms, Science, 1972, pp. 314-322, vol. 177, No. 4046, American Association for the Advancement of Science. [cited by applicant]
Hancock, Host Defence (Cationic) Peptides: What is Their Future Clinical Potential?, Drugs, 1999, pp. 469-473, vol. 57, issue 4, Adis International Limited. [cited by applicant]
Handbook of Pharmaceutical Excipients, Pharmaceutical Press, 2006, pp. 1-945, Fifth Edition, Pharmaceutical Press and the American Pharmacists Association. [cited by applicant]
Harris et al., Polygenic Adaption and Clonal Interference Enabled Sustained Diversity in Experimental Pseudomonas aeruginosa Populations, Mol. Biol. Evol., 2021, pp. 5359-5375, vol. 38, issue 12, Oxford University Press. [cited by applicant]
Heinrich et al., Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes, Chemistry, 2020, pp. 6247-6256, vol. 26, issue 28. [cited by applicant]
Hernando-Amado et al., Antibiotic Resistance Evolution Is Contingent on the Quorum-Sensing Response in Pseudomonas aeruginosa, Mol. Biol. Evol., 2019, pp. 2238-2251, vol. 36, issue 10. [cited by applicant]
Hickman et al., A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels, PNAS, 2005, pp. 14422-14427, vol. 102, No. 40, The National Academy of Sciences of the USA. [cited by applicant]
Honig, Protein Folding: From the Levinthal Paradox to Structure Prediction, J. Mol. Biol., 1999, pp. 283-293, vol. 293, Academic Press. [cited by applicant]
Huangyutitham et al., Subcellular Clustering of the Phosphorylated WspR Response Regulator Protein Stimulates Its Diguanylate Cyclase Activity, mBio, 2013, pp. 1-8, vol. 4, issue 3. [cited by applicant]
Hughes et al., Evolutionary Trajectories to Antibiotic Resistance, Annual Review of Microbiology, 2017, pp. 579-596, vol. 71, Annual Reviews. [cited by applicant]
Hwang et al., Structure-function relationships of antimicrobial peptides, Biochem. Cell Biol., 1998, pp. 235-246, vol. 76, NRC Canada. [cited by applicant]
Ibacache-Quiroga et al., Parallel Evolution of High-Level Aminoglycoside Resistance in [cited by applicant]
Isaacs et al., Inactivation of Herpes Simplex Virus Clinical Isolates by Using a Combination Microbicide, Antimicrobial Agents and Chemotherapy, 2006, pp. 1063-1066, vol. 50, No. 3, American Society for Microbiology. [cited by applicant]
Jennings et al., Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix, PNAS, 2015, pp. 11353-11358, vol. 112, No. 36. [cited by applicant]
Kalia et al., Rational Site-Directed Mutations of the LLP-1 and LLP-2 Lentivirus Lytic Peptide Domains in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41 Indicate Common Functions in Cell-Cell Fusi… [cited by applicant]
Klevens et al., Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002, Public Health Reports, 2007, pp. 160-166, vol. 122. [cited by applicant]
Koenig et al., Effect of the conformation of a peptide from gp41 on binding and domain formation in model membranes, Molecular Membrane Biology, 1995, pp. 77-82, vol. 12, Taylor & Francis. [cited by applicant]
Kumagai et al., Elastic behavior of model membranes with antimicrobial peptides depends on lipid specificity and D-enantiomers, Soft Matter, 2019, pp. 1860-1868, vol. 15, No. 8. [cited by applicant]
Labruere et al., Anti-Methicillin-Resistant [cited by applicant]
Lampi et al., Structural attributes affecting peptide entrapment in PEO brush layers, Colloids Surf B Biointerfaces, 2013, pp. 79-85, vol. 106, Elsevier B.V. [cited by applicant]
Lashua et al., Engineered cationic antimicrobial peptide (eCAP) prevents Pseudomonas aeruginosa biofilm growth on airway epithelial cells, Journal Antimicrobial Chemotherapy, 2016, pp. 2200-2207, vol. 71, Oxford Univers… [cited by applicant]
Lehrer et al., Antibacterial Activity of Microbicidal Cationic Proteins 1 and 2, Natural Peptide Antibiotics of Rabbit ung Macrophages, Infection and Immunity, 1983, pp. 10-14, vol. 42, No. 1, American Society for Micro… [cited by applicant]
Leszczynska et al., Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice, BMC Microbiology, 2009, pp. 1-10, vol. 9, BioMed Cent… [cited by applicant]
Li et al., Structural insights into YfiR sequestering by YfiB in Pseudomonas aeruginosa PAO1, Scientific Reports, 2015, pp. 1-14, vol. 5. [cited by applicant]
Li et al., Antibiofilm peptides as a promising strategy: comparative research, Applied Microbiology and Biotechnology, 2021, pp. 1647-1656, vol. 105, Springer. [cited by applicant]
Lieberman et al., Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes, Nature Genetics, 2011, pp. 1275-1281, vol. 43, No. 12, Nature America, Inc. [cited by applicant]
Lin et al., Prevention of ESKAPE pathogen biofilm formation by antimicrobial peptides WLBU2 and LL37, Int J Antimicrob Agents, 2018, pp. 667-672, vol. 52, issue 5. [cited by applicant]
Ling et al., A new antibiotic kills pathogens without detectable resistance, Nature, 2015, pp. 455-459, vol. 517. [cited by applicant]
Macia et al., Hypermutation Is a Key Factor in Development of Multiple-Antimicrobial Resistance in Pseudomonas aeruginosa Strains Causing Chronic Lung Infections, Antimicrobial Agents and Chemotherapy, 2005, pp. 3382-33… [cited by applicant]
Maclean, Assessing the Potenial for [cited by applicant]
Maclean et al., The evolution of antibiotic resistance, Science, 2019, pp. 1082-1083, vol. 365, issue 6458, AAAS. [cited by applicant]
Mai et al., Efficiency of Protein Transduction Is Cell Type-dependent and Is Enhanced by Dextran Sulfate, The Journal of Biological Chemistry, 2002, pp. 30208-30218, vol. 277, No. 33, The American Society for Biochemist… [cited by applicant]
Malik et al., pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents, Pharmaceuticals, 2016, pp. 1-35, vol. 9, No. 67. [cited by applicant]
Gagne, “Osmolarity.” ScienceDirect, 2014, Section 2.1.6. [cited by applicant]
Lashua et al., “Engineered cationic antimicrobial peptide (eCAP) prevents Pseudomonas aeruginosa biofilm growth on airway epithelial cells”, Journal of Antimicrobial Chemotherapy, 2016, pp. 2200-2207, vol. 71. [cited by applicant]
Sanz-Garcia et al., “Mutational Evolution of Pseudomonas aeruginosa Resistance to Ribosome-Targeting Antibiotics”, frontiers in Genetics, 2018, pp. 1-13, vol. 9, Article 451. [cited by applicant]