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 μg 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 ⩾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 ⩾0.5 MIC was sustained for at least 6 h. These results will be informative for the clinical application and evaluation of lysostaphin.
Aires de SousaM.,
CrisóstomoM. I.,
SanchesI. S.,
WuJ. S.,
FuzhongJ.,
TomaszA.,
de LencastreH.2003; Frequent recovery of a single clonal type of multidrug-resistant Staphylococcus aureus from patients in two hospitals in Taiwan and China. J Clin Microbiol 41:159–163[CrossRef]
ClimoM. W.,
EhlertK.,
ArcherG. L.2001; Mechanism and suppression of lysostaphin resistance in oxacillin-resistant Staphylococcus aureus
. Antimicrob Agents Chemother 45:1431–1437[CrossRef]
DajcsJ. J.,
ThibodeauxB. A.,
HumeE. B. H.,
ZhengX.,
SloopG. D.,
O'CallahanR. J.2001; Lysostaphin is effective in treating methicillin-resistant Staphylococcus aureus endophthalmitis in the rabbit. Curr Eye Res 22:451–457[CrossRef]
GoldbergL. M.,
DeFrancoJ. M.,
WatanakunakornC.,
HamburgerM.1967; Studies in experimental staphylococcal endocarditis in dogs. VI. Treatment with lysostaphin. Antimicrob Agents Chemother 7:45–53
KusumaC. M.,
Kokai-KunJ. F.2005; Comparison of four methods for determining lysostaphin susceptibility of various strains of Staphylococcus aureus
. Antimicrob Agents Chemother 49:3256–3263[CrossRef]
MierauI.,
LeijP.,
van SwamI.,
BlommesteinB.,
FlorisE.,
MondJ.,
SmidE. J.2005; Industrial-scale production and purification of a heterologous protein in Lactococcus lactis using the nisin-controlled gene expression system NICE: the case of lysostaphin. Microb Cell Fact 4:15[CrossRef]
National Committee for Clinical Laboratory Standards1999Methods for Determining Bactericidal Activity of Antimicrobial Agents , approved guideline M26-A Wayne, PA: National Committee for Clinical Laboratory Standards;
National Committee for Clinical Laboratory Standards2003aMethods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically , approved standard M7-A6 Wayne, PA: National Committee for Clinical Laboratory Standards;
National Committee for Clinical Laboratory Standards2003bMIC Testing: Supplemental Tables supplement M100-S13 (M7 Wayne, PA: National Committee for Clinical Laboratory Standards;
PatronR. L.,
ClimoM. W.,
GoldsteinB. P.,
ArcherG. L.1999; Lysostaphin treatment of experimental aortic valve endocarditis caused by a Staphylococcus aureus isolate with reduced susceptibility to vancomycin. Antimicrob Agents Chemother 43:1754–1755
von EiffC.,
Kokasi-KunJ. F.,
BeckerK.,
PetersG.2003; In vitro activity of recombinant lysostaphin against Staphylococcus aureus isolates from anterior nares and blood. Antimicrob Agents Chemother 47:3613–3615[CrossRef]
WuB.,
TangY.,
ZhangK.,
ZhangT.,
ZhuJ.,
TanS.2002; Staphylococcus heterogeneously resistant to vancomycin in China and antimicrobial activities of imipenem and vancomycin in combination against it. J Clin Microbiol 40:1109–1112[CrossRef]