PMID- 30193012
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20191122
IS  - 1860-7187 (Electronic)
IS  - 1860-7179 (Print)
IS  - 1860-7179 (Linking)
VI  - 13
IP  - 20
DP  - 2018 Oct 22
TI  - Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in 
      Methicillin-Resistant Staphylococcus epidermidis (MRSE).
PG  - 2240-2248
LID - 10.1002/cmdc.201800433 [doi]
AB  - Staphylococcus epidermidis is one of the most prevalent prokaryotic species on 
      human skin and mucosal membranes that constitute the commensal flora. 
      S. epidermidis has become one of the most common causes of primary bacteremia. 
      Infections are difficult to diagnose because the pathogen has natural niches on 
      human skin and the ability to adhere to inanimate surfaces via biofilms. 
      Alarmingly, S. epidermidis has acquired resistance to many antibiotics, which 
      presents a danger to human health. Known as methicillin-resistant S. epidermidis 
      (MRSE), most clinical isolates of MRSE in North America exhibit beta-lactam 
      resistance primarily due to the presence of mecA, a gene that bestows beta-lactam 
      antibiotic resistance in a manner similar to methicillin-resistant Staphylococcus 
      aureus (MRSA). MecA encodes for expression of penicillin-binding protein 2a 
      (PBP2a), which is absent in beta-lactam susceptible strains of S. epidermidis. We 
      can disable this resistance factor in MRSE with 600-Da branched polyethylenimine 
      (BPEI). Cationic BPEI targets anionic wall teichoic acid (WTA), an essential 
      cofactor for proper functioning of PBP2a. We found that BPEI synergizes the 
      activity of beta-lactam antibiotics against MRSE. Growth curves suggest that the 
      combination of BPEI and oxacillin is bactericidal. Electron micrographs indicate 
      abnormalities in the cellular septa and cell walls of treated samples. Therefore, 
      first-line clinical treatments can be effective against MRSE when used in 
      combination with BPEI.
CI  - (c) 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Lam, Anh K
AU  - Lam AK
AD  - Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson 
      Parkway, Norman, OK, 73019, USA.
FAU - Hill, Melissa A
AU  - Hill MA
AD  - Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson 
      Parkway, Norman, OK, 73019, USA.
FAU - Moen, Erika L
AU  - Moen EL
AD  - Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson 
      Parkway, Norman, OK, 73019, USA.
FAU - Pusavat, Jennifer
AU  - Pusavat J
AD  - Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson 
      Parkway, Norman, OK, 73019, USA.
FAU - Wouters, Cassandra L
AU  - Wouters CL
AD  - Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson 
      Parkway, Norman, OK, 73019, USA.
FAU - Rice, Charles V
AU  - Rice CV
AUID- ORCID: 0000-0003-1424-405X
AD  - Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson 
      Parkway, Norman, OK, 73019, USA.
LA  - eng
GR  - R03 AI142420/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180925
PL  - Germany
TA  - ChemMedChem
JT  - ChemMedChem
JID - 101259013
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Penicillin-Binding Proteins)
RN  - 0 (Teichoic Acids)
RN  - 9002-98-6 (Polyethyleneimine)
RN  - UH95VD7V76 (Oxacillin)
SB  - IM
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Bacterial Proteins/antagonists & inhibitors
MH  - Cell Wall/drug effects
MH  - Drug Synergism
MH  - Methicillin Resistance/*drug effects
MH  - Microbial Sensitivity Tests
MH  - Oxacillin/pharmacology
MH  - Penicillin-Binding Proteins/antagonists & inhibitors
MH  - Polyethyleneimine/*pharmacology
MH  - Staphylococcus epidermidis/*drug effects
MH  - Teichoic Acids/metabolism
PMC - PMC6869378
MID - NIHMS1053518
OTO - NOTNLM
OT  - Staphylococcus epidermidis
OT  - antibiotic resistance
OT  - branched polyethylenimine
OT  - wall teichoic acid
OT  - beta-lactams
COIS- Conflict of interest The authors declare no conflict of interest.
EDAT- 2018/09/08 06:00
MHDA- 2019/09/17 06:00
PMCR- 2019/11/21
CRDT- 2018/09/08 06:00
PHST- 2018/06/28 00:00 [received]
PHST- 2018/09/05 00:00 [revised]
PHST- 2018/09/08 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/09/08 06:00 [entrez]
PHST- 2019/11/21 00:00 [pmc-release]
AID - 10.1002/cmdc.201800433 [doi]
PST - ppublish
SO  - ChemMedChem. 2018 Oct 22;13(20):2240-2248. doi: 10.1002/cmdc.201800433. Epub 2018 
      Sep 25.