Nonclassical Antagonism Between Human Lysozyme and AMPs Against Pseudomonas Aeruginosa

Overview

Journal FEBS Open Bio

Specialty Biology

Date 2021 Jan 22

PMID 33480189

Citations 5

Authors

Ian Blumenthal

Lydia R Davis

Chet M Berman

Karl E Griswold

Affiliations

Soon will be listed here.

Abstract

Combinations of human lysozyme (hLYS) and antimicrobial peptides (AMPs) are known to exhibit either additive or synergistic activity, and as a result, they have therapeutic potential for persistent and antibiotic-resistant infections. We examined hLYS activity against Pseudomonas aeruginosa when combined with six different AMPs. In contrast to prior reports, we discovered that some therapeutically relevant AMPs manifest striking antagonistic interactions with hLYS across particular concentration ranges. We further found that the synthetic AMP Tet009 can inhibit hLYS-mediated bacterial lysis. To the best of our knowledge, these results represent the first observations of antagonism between hLYS and AMPs, and they advise that future development of lytic enzyme and AMP combination therapies considers the potential for antagonistic interactions.

Citing Articles

Diving into drug-screening: zebrafish embryos as an in vivo platform for antimicrobial drug discovery and assessment.

Habjan E, Schouten G, Speer A, van Ulsen P, Bitter W FEMS Microbiol Rev. 2024; 48(3).

PMID: 38684467 PMC: 11078164. DOI: 10.1093/femsre/fuae011.

Synergistic Antimicrobial Action of Lactoferrin-Derived Peptides and Quorum Quenching Enzymes.

Aslanli A, Domnin M, Stepanov N, Efremenko E Int J Mol Sci. 2023; 24(4).

PMID: 36834977 PMC: 9965131. DOI: 10.3390/ijms24043566.

The In Vitro Antimicrobial and Antibiofilm Activities of Lysozyme against Gram-Positive Bacteria.

Liu F, Wang X, Huang L, Wang X, Kong L, Duan J Comput Math Methods Med. 2022; 2022:4559982.

PMID: 35991138 PMC: 9385363. DOI: 10.1155/2022/4559982.

Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.

Escobar-Salom M, Torrens G, Jordana-Lluch E, Oliver A, Juan C Biol Rev Camb Philos Soc. 2022; 97(3):1005-1037.

PMID: 35043558 PMC: 9304279. DOI: 10.1111/brv.12830.

Applications of Lysozyme, an Innate Immune Defense Factor, as an Alternative Antibiotic.

Ferraboschi P, Ciceri S, Grisenti P Antibiotics (Basel). 2021; 10(12).

PMID: 34943746 PMC: 8698798. DOI: 10.3390/antibiotics10121534.

References

Cosgrove S . The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2005; 42 Suppl 2:S82-9. DOI: 10.1086/499406. View

Scanlon T, Teneback C, Gill A, Bement J, Weiner J, Lamppa J . Enhanced antimicrobial activity of engineered human lysozyme. ACS Chem Biol. 2010; 5(9):809-18. PMC: 2942966. DOI: 10.1021/cb1001119. View

Ragland S, Criss A . From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. PLoS Pathog. 2017; 13(9):e1006512. PMC: 5608400. DOI: 10.1371/journal.ppat.1006512. View

Brandenburg K, Weaver Jr A, Karna S, You T, Chen P, Stryk S . Formation of Pseudomonas aeruginosa Biofilms in Full-thickness Scald Burn Wounds in Rats. Sci Rep. 2019; 9(1):13627. PMC: 6754504. DOI: 10.1038/s41598-019-50003-8. View

Hoover D, Wu Z, Tucker K, Lu W, Lubkowski J . Antimicrobial characterization of human beta-defensin 3 derivatives. Antimicrob Agents Chemother. 2003; 47(9):2804-9. PMC: 182640. DOI: 10.1128/AAC.47.9.2804-2809.2003. View

Wittekind M, Schuch R . Cell wall hydrolases and antibiotics: exploiting synergy to create efficacious new antimicrobial treatments. Curr Opin Microbiol. 2016; 33:18-24. DOI: 10.1016/j.mib.2016.05.006. View

Stover C, Pham X, Erwin A, Mizoguchi S, Warrener P, Hickey M . Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000; 406(6799):959-64. DOI: 10.1038/35023079. View

Singh P, Tack B, McCray Jr P, Welsh M . Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol. 2000; 279(5):L799-805. DOI: 10.1152/ajplung.2000.279.5.L799. View

Teneback C, Scanlon T, Wargo M, Bement J, Griswold K, Leclair L . Bioengineered lysozyme reduces bacterial burden and inflammation in a murine model of mucoid Pseudomonas aeruginosa lung infection. Antimicrob Agents Chemother. 2013; 57(11):5559-64. PMC: 3811238. DOI: 10.1128/AAC.00500-13. View

10.

Klockgether J, Cramer N, Wiehlmann L, Davenport C, Tummler B . Pseudomonas aeruginosa Genomic Structure and Diversity. Front Microbiol. 2011; 2:150. PMC: 3139241. DOI: 10.3389/fmicb.2011.00150. View

11.

Lin P, Li Y, Dong K, Li Q . The Antibacterial Effects of an Antimicrobial Peptide Human β-Defensin 3 Fused with Carbohydrate-Binding Domain on Pseudomonas aeruginosa PA14. Curr Microbiol. 2015; 71(2):170-6. DOI: 10.1007/s00284-015-0814-x. View

12.

Odds F . Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother. 2003; 52(1):1. DOI: 10.1093/jac/dkg301. View

13.

Zhang L, Parente J, Harris S, Woods D, Hancock R, Falla T . Antimicrobial peptide therapeutics for cystic fibrosis. Antimicrob Agents Chemother. 2005; 49(7):2921-7. PMC: 1168697. DOI: 10.1128/AAC.49.7.2921-2927.2005. View

14.

Briers Y, Walmagh M, Van Puyenbroeck V, Cornelissen A, Cenens W, Aertsen A . Engineered endolysin-based "Artilysins" to combat multidrug-resistant gram-negative pathogens. mBio. 2014; 5(4):e01379-14. PMC: 4161244. DOI: 10.1128/mBio.01379-14. View

15.

Bucki R, Leszczynska K, Byfield F, Fein D, Won E, Cruz K . Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate. Antimicrob Agents Chemother. 2010; 54(6):2525-33. PMC: 2876363. DOI: 10.1128/AAC.01682-09. View

16.

Hilpert K, Elliott M, Jenssen H, Kindrachuk J, Fjell C, Korner J . Screening and characterization of surface-tethered cationic peptides for antimicrobial activity. Chem Biol. 2009; 16(1):58-69. DOI: 10.1016/j.chembiol.2008.11.006. View

17.

Hilpert K, Elliott M, Volkmer-Engert R, Henklein P, Donini O, Zhou Q . Sequence requirements and an optimization strategy for short antimicrobial peptides. Chem Biol. 2006; 13(10):1101-7. DOI: 10.1016/j.chembiol.2006.08.014. View

18.

Mohammed I, Said D, Nubile M, Mastropasqua L, Dua H . Cathelicidin-Derived Synthetic Peptide Improves Therapeutic Potential of Vancomycin Against . Front Microbiol. 2019; 10:2190. PMC: 6761703. DOI: 10.3389/fmicb.2019.02190. View

19.

Ruden S, Rieder A, Chis Ster I, Schwartz T, Mikut R, Hilpert K . Synergy Pattern of Short Cationic Antimicrobial Peptides Against Multidrug-Resistant . Front Microbiol. 2019; 10:2740. PMC: 6901909. DOI: 10.3389/fmicb.2019.02740. View

20.

Cherkasov A, Hilpert K, Jenssen H, Fjell C, Waldbrook M, Mullaly S . Use of artificial intelligence in the design of small peptide antibiotics effective against a broad spectrum of highly antibiotic-resistant superbugs. ACS Chem Biol. 2008; 4(1):65-74. DOI: 10.1021/cb800240j. View