PMID- 26119274 OWN - NLM STAT- MEDLINE DCOM- 20160229 LR - 20220408 IS - 1095-8673 (Electronic) IS - 0022-4804 (Linking) VI - 199 IP - 2 DP - 2015 Dec TI - Ultrasound microbubbles enhance human beta-defensin 3 against biofilms. PG - 458-69 LID - S0022-4804(15)00610-1 [pii] LID - 10.1016/j.jss.2015.05.030 [doi] AB - BACKGROUND: The infection of orthopedic implantation devices with Staphylococcus has been a serious concern within the biomaterial community. Treatments are not always successful because of antibiotic-resistant bacteria biofilm infection. Recent studies have shown that combination of antibiotics with low-frequency ultrasound (US) can enhance the bactericidal activity effectively against the formation of biofilms in vitro pilot study. Meanwhile, microbubbles evolved as targeted drug-delivery agents can provide nuclei for inertial cavitation and lower the threshold for US-induced cavitation. Human beta-defensin 3 (HBD-3) is a cationic antimicrobial peptide considered particularly promising for future bactericidal employment and has effect on antibiotic-resistant Staphylococcus biofilms. But the effect has not been reported when combined with US-targeted microbubble destruction (UTMD) in vivo. METHODS: In this study, we evaluated the effect of HBD-3 combined with UTMD on two tested Staphylococcus by the spread plate method, crystal violet staining, confocal laser scanning microscopy, scanning electron microscopy, and real-time polymerase chain reaction. RESULTS: In the study, we found that the biofilm densities, the percentage of live cells, and the viable counts of two tested Staphylococcus that recovered from the biofilm on the titanium surface in mice were significantly decreased in the group of the HBD-3 combined with UTMD, compared with those of other groups. Furthermore, in the experiment, we found out that UTMD could enhance HBD-3 activity, which inhibits the biofilm-associated genes expression of icaAD and the methicillin-resistance genes expression of MecA by promoting the icaR expression simultaneously. CONCLUSIONS: The combination of HBD-3 with UTMD can play a significant role on the elimination of the antibiotic-resistant Staphylococcus biofilms in vivo. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Li, Shoumin AU - Li S AD - Department of Orthopaedic Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. FAU - Zhu, Chen AU - Zhu C AD - Department of Orthopaedic Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. FAU - Fang, Shiyuan AU - Fang S AD - Department of Orthopaedic Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. FAU - Zhang, Weiwei AU - Zhang W AD - Department of Geriatrics, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. FAU - He, Nianan AU - He N AD - Department of Ultrasound, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. FAU - Xu, Wei AU - Xu W AD - Department of Orthopaedic Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. FAU - Kong, Rong AU - Kong R AD - Department of Orthopaedic Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. Electronic address: kongrongahslyy@163.com. FAU - Shang, Xifu AU - Shang X AD - Department of Orthopaedic Surgery, Anhui Provincial Hospital of Anhui Medical University, Hefei, China. Electronic address: shangxifuahslyy@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150522 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Bacterial Proteins) RN - 0 (DEFB103A protein, human) RN - 0 (MecA protein, Staphylococcus epidermidis) RN - 0 (Penicillin-Binding Proteins) RN - 0 (beta-Defensins) RN - 0 (mecA protein, Staphylococcus aureus) RN - D1JT611TNE (Titanium) SB - IM MH - Animals MH - Bacterial Proteins/metabolism MH - *Biofilms MH - Drug Evaluation, Preclinical MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Microbial Sensitivity Tests MH - *Microbubbles MH - Microscopy, Confocal MH - Microscopy, Electron, Scanning MH - Penicillin-Binding Proteins MH - Phenotype MH - Prosthesis-Related Infections/*drug therapy MH - Staphylococcus aureus MH - Staphylococcus epidermidis MH - Titanium MH - *Ultrasonic Therapy MH - beta-Defensins/*administration & dosage OTO - NOTNLM OT - Biofilm OT - Microbubbles OT - Mouse OT - Staphylococcus OT - Ultrasound OT - beta-defensin EDAT- 2015/06/30 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/06/30 06:00 PHST- 2014/10/03 00:00 [received] PHST- 2015/04/06 00:00 [revised] PHST- 2015/05/19 00:00 [accepted] PHST- 2015/06/30 06:00 [entrez] PHST- 2015/06/30 06:00 [pubmed] PHST- 2016/03/02 06:00 [medline] AID - S0022-4804(15)00610-1 [pii] AID - 10.1016/j.jss.2015.05.030 [doi] PST - ppublish SO - J Surg Res. 2015 Dec;199(2):458-69. doi: 10.1016/j.jss.2015.05.030. Epub 2015 May 22.