PMID- 37196462
OWN - NLM
STAT- MEDLINE
DCOM- 20230620
LR  - 20230720
IS  - 1873-4367 (Electronic)
IS  - 0927-7765 (Print)
IS  - 0927-7765 (Linking)
VI  - 227
DP  - 2023 Jul
TI  - Surfaces modified with small molecules that interfere with nucleotide signaling 
      reduce Staphylococcus epidermidis biofilm and increase the efficacy of 
      ciprofloxacin.
PG  - 113345
LID - S0927-7765(23)00223-0 [pii]
LID - 10.1016/j.colsurfb.2023.113345 [doi]
AB  - Staphylococcus epidermidis are common bacteria associated with biofilm related 
      infections on implanted medical devices. Antibiotics are often used in combating 
      such infections, but they may lose their efficacy in the presence of biofilms. 
      Bacterial intracellular nucleotide second messenger signaling plays an important 
      role in biofilm formation, and interference with the nucleotide signaling 
      pathways provides a possible way to control biofilm formation and to increase 
      biofilm susceptibility to antibiotic therapy. This study synthesized small 
      molecule derivates of 4-arylazo-3,5-diamino-1 H-pyrazole (named as SP02 and SP03) 
      and found these molecules inhibited S. epidermidis biofilm formation and induced 
      biofilm dispersal. Analysis of bacterial nucleotide signaling molecules showed 
      that both SP02 and SP03 significantly reduced cyclic dimeric adenosine 
      monophosphate (c-di-AMP) levels in S. epidermidis at doses as low as 25 microM while 
      having significant effects on multiple nucleotides signaling including cyclic 
      dimeric guanosine monophosphate (c-di-GMP), c-di-AMP, and cyclic adenosine 
      monophosphate (cAMP) at high doses (100 microM or greater). We then tethered these 
      small molecules to polyurethane (PU) biomaterial surfaces and investigated 
      biofilm formation on the modified surfaces. Results showed that the modified 
      surfaces significantly inhibited biofilm formation during 24 h and 7-day 
      incubations. The antibiotic ciprofloxacin was used to treat these biofilms and 
      the efficacy of the antibiotic (2 microg/mL) was found to increase from 94.8% on 
      unmodified PU surfaces to > 99.9% on both SP02 and SP03 modified surfaces (>3 log 
      units). Results demonstrated the feasibility of tethering small molecules that 
      interfere with nucleotide signaling onto polymeric biomaterial surfaces and in a 
      way that interrupts biofilm formation and increases antibiotic efficacy for S. 
      epidermidis infections.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Xu, Li-Chong
AU  - Xu LC
AD  - Department of Surgery, The Pennsylvania State University College of Medicine, 
      Hershey, PA 17033, USA. Electronic address: lxx5@psu.edu.
FAU - Ochetto, Alyssa
AU  - Ochetto A
AD  - Department of Biological and Biomedical Sciences, Rowan University, Glassboro, NJ 
      08028, USA.
FAU - Chen, Chen
AU  - Chen C
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA.
FAU - Sun, Dongxiao
AU  - Sun D
AD  - Department of Pharmacology, Mass Spectrometry Core Facilities (RRID: SCR_017831), 
      The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
FAU - Allcock, Harry R
AU  - Allcock HR
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA.
FAU - Siedlecki, Christopher A
AU  - Siedlecki CA
AD  - Department of Surgery, The Pennsylvania State University College of Medicine, 
      Hershey, PA 17033, USA; Department of Biomedical Engineering, The Pennsylvania 
      State University College of Medicine, Hershey, PA 17033, USA.
LA  - eng
GR  - R01 HL153231/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20230512
PL  - Netherlands
TA  - Colloids Surf B Biointerfaces
JT  - Colloids and surfaces. B, Biointerfaces
JID - 9315133
RN  - 5E8K9I0O4U (Ciprofloxacin)
RN  - 0 (Nucleotides)
RN  - 0 (Anti-Bacterial Agents)
RN  - H2D2X058MU (Cyclic GMP)
RN  - 0 (Biocompatible Materials)
RN  - 415SHH325A (Adenosine Monophosphate)
SB  - IM
MH  - *Ciprofloxacin/pharmacology
MH  - *Staphylococcus epidermidis
MH  - Nucleotides
MH  - Biofilms
MH  - Anti-Bacterial Agents/pharmacology
MH  - Cyclic GMP/metabolism/pharmacology
MH  - Biocompatible Materials/pharmacology
MH  - Adenosine Monophosphate
PMC - PMC10355139
MID - NIHMS1902697
OTO - NOTNLM
OT  - Biofilm
OT  - C-di-AMP
OT  - C-di-GMP
OT  - Efficacy of antibiotics
OT  - Nucleotide
OT  - Small molecule
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/18 01:07
MHDA- 2023/06/20 06:41
PMCR- 2024/07/01
CRDT- 2023/05/17 18:05
PHST- 2022/11/12 00:00 [received]
PHST- 2023/03/30 00:00 [revised]
PHST- 2023/05/11 00:00 [accepted]
PHST- 2024/07/01 00:00 [pmc-release]
PHST- 2023/06/20 06:41 [medline]
PHST- 2023/05/18 01:07 [pubmed]
PHST- 2023/05/17 18:05 [entrez]
AID - S0927-7765(23)00223-0 [pii]
AID - 10.1016/j.colsurfb.2023.113345 [doi]
PST - ppublish
SO  - Colloids Surf B Biointerfaces. 2023 Jul;227:113345. doi: 
      10.1016/j.colsurfb.2023.113345. Epub 2023 May 12.