Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms

被引:225
作者
Jefferson, KK
Goldmann, DA
Pier, GB
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA
关键词
D O I
10.1128/AAC.49.6.2467-2473.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
When bacteria assume the biofilm mode of growth, they can tolerate levels of antimicrobial agents 10 to 1,000 times higher than the MICs of genetically equivalent planktonic bacteria. The properties of biofilms that give rise to antibiotic resistance are only partially understood. Inhibition of antibiotic penetration into the biofilm may play a role, but this has not been proven directly. In this report, penetration of the glycopeptide antibiotic vancomycin into viable Staphylococcus aureus biofilms was analyzed by confocal scanning laser microscopy using a fluorescently labeled derivative of the drug. We found that while vancomycin bound to free-floating bacteria in water within 5 min, it took more than 1 h to bind to cells within the deepest layers of a biofilm. These results indicate that the antibiotic is transported through the depth of the biofilm but that the rate is significantly reduced with respect to its transport through flowing water. This suggests that, whereas planktonic bacteria were rapidly exposed to a full bolus of vancomycin, the bacteria in the deeper layers of the biofilm were exposed to a gradually increasing dose of the drug due to its reduced rate of penetration. This gradual exposure may allow the biofilm bacteria to undergo stress-induced metabolic or transcriptional changes that increase resistance to the antibiotic. We also investigated the role of poly-N-acetylglucosamine, an important component of the S. aureus biofilm matrix, and found that its production was not involved in the observed decrease in the rate of vancomycin penetration.
引用
收藏
页码:2467 / 2473
页数:7
相关论文
共 23 条
[1]  
Bartley Judene, 2002, Infect Control Hosp Epidemiol, V23, P480
[2]   Microarray-based analysis of the Staphylococcus aureus σB regulon [J].
Bischoff, M ;
Dunman, P ;
Kormanec, J ;
Macapagal, D ;
Murphy, E ;
Mounts, W ;
Berger-Bächi, B ;
Projan, S .
JOURNAL OF BACTERIOLOGY, 2004, 186 (13) :4085-4099
[3]  
*CECP, 2004, MMWR-MORBID MORTAL W, V53, P322
[4]  
*CECP, 2002, MMWR-MORBID MORTAL W, V51, P902
[5]   Bacterial biofilms: A common cause of persistent infections [J].
Costerton, JW ;
Stewart, PS ;
Greenberg, EP .
SCIENCE, 1999, 284 (5418) :1318-1322
[6]   The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation [J].
Cramton, SE ;
Gerke, C ;
Schnell, NF ;
Nichols, WW ;
Götz, F .
INFECTION AND IMMUNITY, 1999, 67 (10) :5427-5433
[7]   Control of cell morphogenesis in bacteria: Two distinct ways to make a rod-shaped cell [J].
Daniel, RA ;
Errington, J .
CELL, 2003, 113 (06) :767-776
[8]   Biofilm formation: A clinically relevant microbiological process [J].
Donlan, RM .
CLINICAL INFECTIOUS DISEASES, 2001, 33 (08) :1387-1392
[9]   DIFFUSION OF RIFAMPIN AND VANCOMYCIN THROUGH A STAPHYLOCOCCUS-EPIDERMIDIS BIOFILM [J].
DUNNE, WM ;
MASON, EO ;
KAPLAN, SL .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (12) :2522-2526
[10]   STAPHYLOCOCCUS-EPIDERMIDIS EXTRACTED SLIME INHIBITS THE ANTIMICROBIAL ACTION OF GLYCOPEPTIDE ANTIBIOTICS [J].
FARBER, BF ;
KAPLAN, MH ;
CLOGSTON, AG .
JOURNAL OF INFECTIOUS DISEASES, 1990, 161 (01) :37-40