Study of the antimicrobial activity of cationic carbosilane dendrimers against clinical strains of multidrug-resistant bacteria and their biofilms

Front Cell Infect Microbiol. 2023 Oct 10:13:1203991. doi: 10.3389/fcimb.2023.1203991. eCollection 2023.

Abstract

Introduction: Antimicrobial Resistance is a serious public health problem, which is aggravated by the ability of the microorganisms to form biofilms. Therefore, new therapeutic strategies need to be found, one of them being the use of cationic dendritic systems (dendrimers and dendrons).

Methods: The aim of this study is to analyze the in vitro antimicrobial efficacy of six cationic carbosilane (CBS) dendrimers and one dendron with peripheral ammonium groups against multidrug-resistant bacteria, some of them isolated hospital strains, and their biofilms. For this purpose, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC) and minimum eradication biofilm concentration (MBEC) studies were carried out. In addition, the cytotoxicity on Hela cells of those compounds that proved to be the most effective was analyzed.

Results: All the tested compounds showed in vitro activity against the planktonic forms of methicillin-resistant Staphylococcus aureus and only the dendrimers BDSQ017, BDAC-001 and BDLS-001 and the dendron BDEF-130 against their biofilms. On the other hand, only the dendrimers BDAC 001, BDLS-001 and BDJS-049 and the dendron BDEF-130 were antibacterial in vitro against the planktonic forms of multidrug-resistant Pseudomonas aeruginosa, but they lacked activity against their preformed biofilms. In addition, the dendrimers BDAC-001, BDLS-001 and BDSQ-017 and the dendron BDEF-130 exhibited a good profile of cytotoxicity in vitro.

Discussion: Our study demonstrates the possibility of using the four compounds mentioned above as possible topical antimicrobials against the clinical and reference strains of multidrug-resistant bacteria.

Keywords: antibacterial; biofilms; carbosilane dendrimers and dendrons; multiresistant bacteria; quaternary ammonium salts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / pharmacology
  • Biofilms
  • Dendrimers* / pharmacology
  • HeLa Cells
  • Humans
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests

Substances

  • Dendrimers
  • carbosilane
  • dendron
  • Anti-Bacterial Agents
  • Anti-Infective Agents

Grants and funding

This work was supported by the Ministry of Science and Innovation (ref. PID2020-112924RB-I00), Comunidad Autónoma de Madrid and European funding from FEDER program (CAM_Radioprotect_P2022BMD-7406) and grant EPU-INV/2020/014 (CAM, UAH). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. Also, this work form part of the research project “The search for new compounds with antimicrobial properties against multidrug-resistant pathogens or with ineffective treatments” from the Príncipe de Asturias Universitary Hospital.