PMID- 37882623
OWN - NLM
STAT- MEDLINE
DCOM- 20231113
LR  - 20231115
IS  - 2373-8227 (Electronic)
IS  - 2373-8227 (Linking)
VI  - 9
IP  - 11
DP  - 2023 Nov 10
TI  - Confronting the Threat: Designing Highly Effective bis-Benzimidazolium Agents to 
      Overcome Biofilm Persistence and Antimicrobial Resistance.
PG  - 2202-2214
LID - 10.1021/acsinfecdis.3c00289 [doi]
AB  - The objective of this study is to take the initial steps toward developing novel 
      antibiotics to counteract the escalating problem of antimicrobial and bacterial 
      persistence, particularly in relation to biofilms. Our approach involves 
      emulating the structural characteristics of cationic antimicrobial peptides. To 
      circumvent resistance development, we have designed a library of 
      bis-benzimidazolium salts that selectively target the microbial membranes in a 
      nonspecific manner. To explore their structure-activity relationship, we 
      conducted experiments using these compounds on various pathogens known for their 
      resistance to conventional antibiotics, including Gram-positive 
      methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant 
      Enterococcus faecium (VRE), and Gram-negative Escherichia coli (E. coli). 
      Notably, two bis-benzimidazolium salts exhibited robust antimicrobial activity 
      while maintaining a high level of selectivity compared with mammalian cells. Our 
      investigations revealed significant antibiofilm activity, as these compounds 
      rapidly acted against established biofilms. In addition, bis-benzimidazolium 
      compounds exhibited consistent results in resistance development and 
      cross-resistance studies. Consequently, amphiphilic bis-benzimidazolium salts 
      hold promise as potential candidates to combat resistance-associated infections.
FAU - Petit, Maude
AU  - Petit M
AD  - Departement de Chimie, Faculte des Arts et des Sciences, Universite de Montreal, 
      Campus MIL, 1375, Ave. Therese Lavoie-Roux, Montreal, Quebec H2 V 0B3, Canada.
FAU - Tessier, Jeremie
AU  - Tessier J
AD  - Departement de Chimie, Faculte des Arts et des Sciences, Universite de Montreal, 
      Campus MIL, 1375, Ave. Therese Lavoie-Roux, Montreal, Quebec H2 V 0B3, Canada.
AD  - College Bois-de-Boulogne, 10555 Ave. de Bois-de-Boulogne, Montreal H4N 1L4, 
      Canada.
FAU - Sahli, Celia
AU  - Sahli C
AUID- ORCID: 0000-0002-5548-4909
AD  - Departement de Chimie, Faculte des Arts et des Sciences, Universite de Montreal, 
      Campus MIL, 1375, Ave. Therese Lavoie-Roux, Montreal, Quebec H2 V 0B3, Canada.
AD  - CNRS-UMR 7086, Interfaces, Traitements, Organisation et Dynamique des Systemes 
      (ITODYS), Universite Paris Cite, Paris 75013 , France.
FAU - Schmitzer, Andreea R
AU  - Schmitzer AR
AUID- ORCID: 0000-0002-3806-9076
AD  - Departement de Chimie, Faculte des Arts et des Sciences, Universite de Montreal, 
      Campus MIL, 1375, Ave. Therese Lavoie-Roux, Montreal, Quebec H2 V 0B3, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231026
PL  - United States
TA  - ACS Infect Dis
JT  - ACS infectious diseases
JID - 101654580
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Salts)
RN  - 0 (Anti-Infective Agents)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology/chemistry
MH  - *Methicillin-Resistant Staphylococcus aureus
MH  - Salts
MH  - Escherichia coli
MH  - Drug Resistance, Bacterial
MH  - *Anti-Infective Agents/pharmacology
MH  - *Bacterial Infections
MH  - Biofilms
MH  - Mammals
OTO - NOTNLM
OT  - antibiofilm agents
OT  - antimicrobials
OT  - bacterial resistance
OT  - bis-benzimidazolium salts
OT  - cross-resistance
OT  - quaternary ammoniums
EDAT- 2023/10/26 12:42
MHDA- 2023/11/13 06:42
CRDT- 2023/10/26 09:33
PHST- 2023/11/13 06:42 [medline]
PHST- 2023/10/26 12:42 [pubmed]
PHST- 2023/10/26 09:33 [entrez]
AID - 10.1021/acsinfecdis.3c00289 [doi]
PST - ppublish
SO  - ACS Infect Dis. 2023 Nov 10;9(11):2202-2214. doi: 10.1021/acsinfecdis.3c00289. 
      Epub 2023 Oct 26.