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International journal of molecular sciences
Jul 06, 2021;22 (14):

Bactericidal Activity of a Self-Biodegradable Lysine-Containing Dendrimer against Clinical Isolates of Genus.

Silvana Alfei, Debora Caviglia, Gabriella Piatti, Guendalina Zuccari, Anna Maria Schito
Author Information
  1. Silvana Alfei: Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy. ORCID
  2. Debora Caviglia: Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genova, Italy.
  3. Gabriella Piatti: Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genova, Italy.
  4. Guendalina Zuccari: Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy. ORCID
  5. Anna Maria Schito: Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genova, Italy.
PMID: 34298891 DOI: 10.3390/ijms22147274

Abstract

The genus consists of Gram-negative obligate aerobic pathogens, including clinically relevant species, such as , which frequently cause hospital infections, affecting debilitated patients. The growing resistance to antimicrobial therapies shown by is reaching unacceptable levels in clinical practice, and there is growing concern that the serious conditions it causes may soon become incurable. New therapeutic possibilities are, therefore, urgently needed to circumvent this important problem. Synthetic cationic macromolecules, such as cationic antimicrobial peptides (AMPs), which act as membrane disrupters, could find application in these conditions. A lysine-modified cationic polyester-based dendrimer (G5-PDK), capable of electrostatically interacting with bacterial surfaces as AMPs do, has been synthesized and characterized here. Given its chemical structure, similar to that of a fifth-generation lysine containing dendrimer (G5K) with a different , and previously found inactive against Gram-positive bacterial species and , the new G5-PDK was also ineffective on the species mentioned above. In contrast, it showed minimum inhibitory concentration values (MICs) lower than reported for several AMPs and other synthetic cationic compounds on genus (3.2-12.7 µM). Time-kill experiments on , , and ascertained the rapid bactericidal effects of G5-PDK, while subsequent bacterial regrowth supported its self-biodegradability.

Keywords

A. baumannii A. johnsonii A. pittii A. ursingii MIC values (MICs) bactericidal activity cationic lysine-modified dendrimer multi-drug resistant (MDR) clinical isolates self-biodegradability time-kill experiments

References

Int J Antimicrob Agents. 2016 Sep;48(3):331-6 [PMID: 27449542]
PLoS One. 2016 Mar 02;11(3):e0150642 [PMID: 26934182]
Antioxidants (Basel). 2020 Jan 06;9(1): [PMID: 31935872]
Nanomaterials (Basel). 2021 Apr 10;11(4): [PMID: 33920180]
J Hosp Infect. 2006 Nov;64(3):282-7 [PMID: 16930770]
Front Bioeng Biotechnol. 2020 Feb 14;8:55 [PMID: 32117934]
Drug Deliv Transl Res. 2020 Feb;10(1):259-270 [PMID: 31628606]
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3477-82 [PMID: 23345420]
Bioconjug Chem. 2000 Sep-Oct;11(5):637-45 [PMID: 10995206]
Polymers (Basel). 2021 Apr 02;13(7): [PMID: 33918374]
Diagn Microbiol Infect Dis. 2017 Jan;87(1):79-86 [PMID: 27789057]
Front Microbiol. 2012 Apr 23;3:148 [PMID: 22536199]
Clin Microbiol Rev. 2008 Jul;21(3):449-65 [PMID: 18625681]
Biomacromolecules. 2012 May 14;13(5):1554-63 [PMID: 22497522]
Clin Microbiol Infect. 2005 Nov;11(11):868-73 [PMID: 16216100]
Biomacromolecules. 2017 Dec 11;18(12):4323-4330 [PMID: 29131611]
Curr Opin Pharmacol. 2006 Oct;6(5):468-72 [PMID: 16890021]
Biochem Biophys Res Commun. 2019 Oct 20;518(3):472-478 [PMID: 31443965]
Clin Microbiol Infect. 2012 Apr;18(4):383-7 [PMID: 21672084]
Infect Drug Resist. 2018 Jun 06;11:861-872 [PMID: 29922077]
Lancet Infect Dis. 2008 Dec;8(12):751-62 [PMID: 19022191]
Clin Infect Dis. 2006 Sep 1;43 Suppl 2:S49-56 [PMID: 16894515]
Int J Mol Sci. 2021 May 09;22(9): [PMID: 34065133]
Clin Infect Dis. 2001 Oct 1;33(7):939-46 [PMID: 11528563]
Pharm Res. 2000 Jul;17(7):811-6 [PMID: 10990199]
BMC Infect Dis. 2013 Mar 19;13:142 [PMID: 23509931]
Acta Biomater. 2018 Sep 15;78:78-88 [PMID: 30031912]
Microbiol Mol Biol Rev. 2003 Dec;67(4):593-656 [PMID: 14665678]
Probiotics Antimicrob Proteins. 2019 Mar;11(1):317-324 [PMID: 30043322]
Clin Microbiol Rev. 2017 Jan;30(1):409-447 [PMID: 27974412]
Polymers (Basel). 2021 Feb 09;13(4): [PMID: 33572439]
Nat Rev Microbiol. 2018 Feb;16(2):91-102 [PMID: 29249812]
Polymers (Basel). 2020 May 23;12(5): [PMID: 32456255]
Nanomaterials (Basel). 2020 Oct 14;10(10): [PMID: 33066468]
Nanoscale Adv. 2019 Sep 18;1(10):4148-4157 [PMID: 36132112]
J Med Microbiol. 2011 Mar;60(Pt 3):375-377 [PMID: 21109630]
Antimicrob Agents Chemother. 2015 Dec;59(12):7915-8 [PMID: 26459893]
J Med Microbiol. 2014 Sep;63(Pt 9):1154-1159 [PMID: 24965800]
Expert Rev Anti Infect Ther. 2015 May;13(5):567-73 [PMID: 25850806]
ACS Nano. 2015 Jul 28;9(7):7195-206 [PMID: 26149286]
Pathog Immun. 2018 Feb 22;3(1):19-43 [PMID: 30993248]
Eur J Biochem. 2002 Jan;269(2):422-30 [PMID: 11856300]
Clin Infect Dis. 1992 Jan;14(1):83-91 [PMID: 1571467]
Biomedica. 2012 Jun;32(2):179-81 [PMID: 23242290]
Int J Antimicrob Agents. 2011 Feb;37(2):129-34 [PMID: 21163629]
Clin Infect Dis. 2008 Apr 15;46(8):1254-63 [PMID: 18444865]
PLoS One. 2016 Jun 17;11(6):e0157757 [PMID: 27315107]
Polymers (Basel). 2020 Aug 13;12(8): [PMID: 32823557]
Mol Microbiol. 2018 Jan;107(1):47-56 [PMID: 29114953]
Chem Sci. 2015 Nov 1;6(11):6385-6391 [PMID: 30090258]
ACS Appl Mater Interfaces. 2019 Sep 18;11(37):33559-33572 [PMID: 31424189]
mBio. 2015 May 19;6(3):e00478-15 [PMID: 25991684]
J Antimicrob Chemother. 2000 Nov;46(5):807-10 [PMID: 11062203]
J Clin Microbiol. 2002 Jul;40(7):2696-7 [PMID: 12089313]
Eur J Clin Microbiol Infect Dis. 2007 Dec;26(12):857-68 [PMID: 17701432]
Crit Rev Microbiol. 1996;22(3):139-80 [PMID: 8894399]

MeSH Term

Acinetobacter
Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Dendrimers
Drug Resistance, Multiple, Bacterial
Enterobacteriaceae
Lysine
Microbial Sensitivity Tests

Chemicals

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Dendrimers
Lysine
Journal Article

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