In vitro activity of recombinant lysostaphin against Staphylococcus aureus isolates from hospitals in Beijing, China.
Lysostaphin is a glycylglycine endopeptidase. It cleaves the pentaglycine cross-bridge structure unique to the staphylococcal cell wall and is considered to be a potential drug for Staphylococcus aureus. In the present study, the in vitro activity of recombinant lysostaphin was investigated in 257 S. aureus isolates collected from hospital patients in Beijing, China, by determination of MIC and minimum bactericidal concentration (MBC) and a time-kill curve test. An agar dilution method was used for MIC determination in all of the isolates and a macrobroth dilution method was employed to verify MIC values for a subset of the isolates. All of the S. aureus strains were sensitive to the recombinant lysostaphin with MICs ranging from 0.03 to 2 microg ml(-1) in the agar dilution assay. The antibacterial activity of lysostaphin was greater than that of vancomycin and other reference agents. For most of the isolates, the MICs from the agar dilution method were higher than those from the broth dilution method. The MBCs of lysostaphin in the test isolates were between 1- and 8-fold higher than their MIC values. Bactericidal activity (>99.9 % reduction) was observed after 2 h exposure of the isolates to lysostaphin at concentrations of > or =0.5 MIC. Lysostaphin showed a rapid bactericidal activity against the test strains of meticillin-susceptible S. aureus and meticillin-resistant S. aureus. Its activity at > or =0.5 MIC was sustained for at least 6 h. These results will be informative for the clinical application and evaluation of lysostaphin.
Yang
Xin-Yi
XY
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Li
Cong-Ran
CR
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Lou
Ren-Hui
RH
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Wang
Yue-Ming
YM
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Zhang
Wei-Xin
WX
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Chen
Hui-Zhen
HZ
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Huang
Qing-Shan
QS
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
Han
Yan-Xing
YX
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Jiang
Jian-Dong
JD
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
You
Xue-Fu
XF
Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D002681:China; D003428:Cross Infection / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008248:Lysostaphin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D011994:Recombinant Proteins; D014640:Vancomycin; D008248:Lysostaphin