PMID- 32484998
OWN - NLM
STAT- MEDLINE
DCOM- 20210202
LR  - 20211203
IS  - 1554-527X (Electronic)
IS  - 0736-0266 (Print)
IS  - 0736-0266 (Linking)
VI  - 38
IP  - 12
DP  - 2020 Dec
TI  - Direct antimicrobial activity of cationic amphipathic peptide WLBU2 against 
      Staphylococcus aureus biofilms is enhanced in physiologic buffered saline.
PG  - 2657-2663
LID - 10.1002/jor.24765 [doi]
AB  - Periprosthetic joint infection of total knee arthroplasties represents a major 
      challenge to the field of orthopedic surgery. These infections are commonly 
      associated with antibiotic-tolerant Staphylococcus aureus biofilms. Engineered 
      cationic amphipathic peptide WLBU2 has shown the ability to kill 
      antibiotic-resistant pathogens and drug-tolerant bacterial biofilms. The novelty 
      of using WLBU2 during the direct irrigation and debridement of periprosthetic 
      joint infections led our group to investigate the optimal washout conditions for 
      treatment of S. aureus biofilms. S. aureus mature biofilms were grown on metal 
      implant material and treated with WLBU2 dissolved in differing irrigation 
      solvents. Mature biofilms were treated both in vitro as well as in a 
      periprosthetic joint infection murine model. WLBU2 activity against S. aureus 
      biofilms was increased when dissolved in diphosphate-buffered saline (dPBS) with 
      pH of 7.0 compared with normal saline with pH of 5.5. WLBU2 activity was 
      decreased in acidic dPBS and increased in alkaline dPBS. WLBU2 activity could be 
      decreased in hypertonic dPBS and increased in hypotonic dPBS. WLBU2 dissolved in 
      less acidic dPBS displayed increased efficacy in treating periprosthetic joint 
      infection (PJI) implants ex vivo. WLBU2 demonstrated the ability to eliminate PJI 
      associated S. aureus biofilms on arthroplasty material. The efficacy of 
      engineered cationic amphipathic peptide WLBU2 for intraoperative elimination of 
      S. aureus biofilms can be further optimized when kept in a less acidic and more 
      physiologic pH adjusted saline. Understanding optimal physical washout conditions 
      are vital for the success of WLBU2 in treating S. aureus biofilms in PJI clinical 
      trials going forward.
CI  - (c) 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.
FAU - Mandell, Jonathan B
AU  - Mandell JB
AUID- ORCID: 0000-0002-5804-9822
AD  - Arthritis and Arthroplasty Design Laboratory, Department of Orthopaedic Surgery, 
      University of Pittsburgh, Pittsburgh, Pennsylvania.
AD  - Department of Infectious Diseases and Microbiology, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - A Koch, John
AU  - A Koch J
AUID- ORCID: 0000-0001-5692-7970
AD  - Arthritis and Arthroplasty Design Laboratory, Department of Orthopaedic Surgery, 
      University of Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Deslouches, Berthony
AU  - Deslouches B
AD  - Department of Environmental and Occupational Health, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Urish, Kenneth L
AU  - Urish KL
AUID- ORCID: 0000-0002-4511-1308
AD  - Arthritis and Arthroplasty Design Laboratory, Department of Orthopaedic Surgery, 
      University of Pittsburgh, Pittsburgh, Pennsylvania.
AD  - The Bone and Joint Center, Magee Womens Hospital, University of Pittsburgh 
      Medical Center, Pittsburgh, Pennsylvania.
AD  - Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.
AD  - Clinical and Translational Science Institute, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
AD  - Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, 
      Pennsylvania.
LA  - eng
GR  - K08 AR071494/AR/NIAMS NIH HHS/United States
GR  - KL2 TR001856/TR/NCATS NIH HHS/United States
GR  - R01 GM125917/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200609
PL  - United States
TA  - J Orthop Res
JT  - Journal of orthopaedic research : official publication of the Orthopaedic 
      Research Society
JID - 8404726
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Saline Solution)
RN  - 0 (WLBU2 peptide)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides/*administration & dosage
MH  - Biofilms/*drug effects
MH  - Drug Evaluation, Preclinical
MH  - Female
MH  - Hydrogen-Ion Concentration
MH  - Mice
MH  - Osmolar Concentration
MH  - Prosthesis-Related Infections/*drug therapy
MH  - Saline Solution
MH  - Staphylococcus aureus/*drug effects
PMC - PMC7665995
MID - NIHMS1615220
OTO - NOTNLM
OT  - antimicrobial peptide
OT  - biofilm, periprosthetic joint infection, Staphylococcus aureus
EDAT- 2020/06/03 06:00
MHDA- 2021/02/03 06:00
PMCR- 2021/12/01
CRDT- 2020/06/03 06:00
PHST- 2020/01/04 00:00 [received]
PHST- 2020/04/30 00:00 [revised]
PHST- 2020/05/25 00:00 [accepted]
PHST- 2020/06/03 06:00 [pubmed]
PHST- 2021/02/03 06:00 [medline]
PHST- 2020/06/03 06:00 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - 10.1002/jor.24765 [doi]
PST - ppublish
SO  - J Orthop Res. 2020 Dec;38(12):2657-2663. doi: 10.1002/jor.24765. Epub 2020 Jun 9.