Open AccessAntibiofilm Activity of GlmU Enzyme Inhibitors against Catheter-Associated Uropathogens
Author(s) -
Euan Burton,
Purushottam V. Gawande,
Nandadeva Yakandawala,
Karen LoVetri,
George G. Zhanel,
Tony Romeo,
Albert D. Friesen,
Srinivasa Madhyastha
Publication year - 2006
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.50.5.1835-1840.2006
Subject(s) - protamine sulfate , biofilm , microbiology and biotechnology , staphylococcus epidermidis , enterococcus faecalis , chemistry , pseudomonas aeruginosa , klebsiella pneumoniae , protamine , staphylococcus aureus , escherichia coli , bacteria , biology , biochemistry , heparin , gene , genetics
The colonization of uropathogenic bacteria on urinary catheters resulting in biofilm formation frequently leads to the infection of surrounding tissue and often requires removal of the catheter. Infections associated with biofilms are difficult to treat since they may be more than 1,000 times more resistant to antibiotics than their planktonic counterparts. We have developed an antibiofilm composition comprising anN -acetyl-d -glucosamine-1-phosphate acetyltransferase (GlmU) inhibitor and protamine sulfate, a cationic polypeptide. The antibiofilm activity of GlmU inhibitors, such as iodoacetamide (IDA),N -ethyl maleimide (NEM), and NEM analogs, includingN -phenyl maleimide,N ,N ′-(1,2-phenylene)dimaleimide (oPDM), andN -(1-pyrenyl)maleimide (PyrM), was tested against that of catheter-associated uropathogens. Both IDA and NEM inhibited biofilm formation inEscherichia coli . All NEM analogs showed antibiofilm activity against clinical isolates ofE. coli ,Pseudomonas aeruginosa ,Klebsiella pneumoniae ,Staphylococcus epidermidis , andEnterococcus faecalis . The combination of oPDM with protamine sulfate (PS) enhanced its antibiofilm activity and reduced its effective concentration to as low as 12.5 μM. In addition, we found that the in vitro inhibitory activity of oPDM-plus-PS-coated silicone catheters againstP. aeruginosa andS. epidermidis colonization was superior to that of catheters coated with silver hydrogel. Confocal scanning laser microscopy further confirmed that the oPDM-plus-PS-coated silicone catheters were almost free from bacterial colonization. Thus, a broad-spectrum antibiofilm composition comprising a GlmU inhibitor and protamine sulfate shows promise for use in anti-infective coatings for medical devices, including urinary catheters.