title: Toward a Molecular Understanding of the Antibacterial Mechanism of Copper-Bearing Titanium Alloys against Staphylococcus aureus.
abstract: The antibacterial mechanism of the Cu-containing materials has not been fully understood although such understanding is crucial for the sustained clinical use of Cu-containing antibacterial materials such as bone implants. The aim of this study is to investigate the molecular mechanisms by which the Gram-positive Staphylococcus aureus is inactivated through Cu-bearing titanium alloys (Ti6Al4V5Cu). Cu ions released from the alloys are found to contribute to lethal damage of bacteria. They destroy the permeability of the bacterial membranes, resulting in the leakage of reducing sugars and proteins from the cells. They also promote the generation of bacteria-killing reactive oxygen species (ROS). The ROS production is confirmed by several assays including fluorescent staining of intracellular oxidative stress, detection of respiratory chain activity, and measurement of the levels of lipid peroxidation, catalase, and glutathione. Furthermore, the released Cu ions show obvious genetic toxicity by interfering the replication of nuc (species-specific) and 16SrRNA genes, but with no effect on the genome integrity. All of these effects lead to the antibacterial effect of Ti6Al4V5Cu. Collectively, our work reconciles the conflicting antibacterial mechanisms of Cu-bearing metallic materials or nanoparticles reported in the literature and highlights the potential use of Ti6Al4V5Cu alloys in inhibiting bacterial infections.
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, 510010, China.|State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK, 73019, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, 510010, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, 510010, China.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, 510010, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, 510010, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Institute of Applied Bioresource Research, College of Animal Science, Zhejiang University, Yuhangtang Road 866, Hangzhou, 310058, China.
authors.forename: Mingying
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, 510010, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK, 73019, USA.|School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Mao
mesh_terms: D000497:Alloys / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D007477:Ions; D015227:Lipid Peroxidation / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects*; D014025:Titanium / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D000497:Alloys; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015415:Biomarkers; D007477:Ions; D009153:Mutagens; C031462:titanium alloy (TiAl6V4); D003300:Copper; D014025:Titanium; D010088:Oxidoreductases
keywords: Staphylococcus aureus; antibacterial mechanism; copper; titanium alloys