Anti-biofilm and anti-adherence activity of Glm-U inhibitors

Ethel Suman, Sushma Janet D'Souza, Pyari Jacob, M. R. Sushruth, M. Shashidhar Kotian

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Intravascular catheters and urinary catheters are an important source of hospital-acquired infections. Many microorganisms colonize indwelling catheters, including central venous catheters (CVCs) forming biofilms and cause infections that are difficult to treat. Although various methods have been employed to reduce biofilms, enzymes involved in bacterial cell wall synthesis could provide novel targets for the development of anti-biofilm agents. N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and catalyzes the formation of uridine-diphospho-N- acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolysaccharide biosynthesis of Gram-positive and Gram-negative bacteria. Previous study has been conducted on the anti-biofilm effect of GlmU inhibitors such as N-ethyl maleimide (NEM) and NEM analogs along with a cationic polypeptide protamine sulfate (PS), which enhanced its anti-biofilm activity. AIM: The present study aimed at finding the effect of sub-inhibitory concentrations of N-ethyl maleimide (NEM) and protamine sulfate (PS) on the biofilms produced by Pseudomonas aeruginosa and Enterococcus spp. isolated from cases of catheter-associated UTI as well as Klebsiella pneumoniae and Staphylococcus aureus isolated from cases of catheter-related bloodstream infections (CRBSI). Materials and Methods: In order to enhance the activity of NEM and to develop a broad-spectrum anti-microbial composition, NEM (50 μg/ml) was combined with protamine sulfate (50 μg/ml) and tested for anti-biofilm activity using a standard quantitative biofilm assay method. Results and Conclusion: It was observed that NEM had no effect on the biofilm produced by Pseudomonas aeruginosa as well as by Enterococcus spp. NEM also caused a significant decrease in biofilm production by Staphylococcus aureus while it had no effect on the biofilm produced by Klebsiella pneumoniae. There was a significant synergistic inhibitory effect on Staphylococcus aureus and Enterococcus spp., whereas Pseudomonas aeruginosa and Klebsiella pneumoniae remained unaffected. Combination of GlmU inhibitor-plus-protamine sulfate failed to significantly reduce bacterial adherence of Pseudomonas aeruginosa and Klebsiella pneumoniae to catheter and cannula pieces, respectively. We found that the GlmU inhibitor was mainly effective in preventing the adherence and biofilm formation by gram-positive organisms. The combination of NEM and protamine sulfate may, therefore, be tried as anti-infective coatings for medical devices such as catheters and cannulas, and thus help in overcoming microbial resistance in the current era of increasing device-associated hospital infections.

Original languageEnglish
Pages (from-to)387-392
Number of pages6
JournalIndian Journal of Medical Sciences
Volume65
Issue number9
DOIs
Publication statusPublished - 01-09-2011

Fingerprint

Biofilms
Protamines
Klebsiella pneumoniae
Pseudomonas aeruginosa
Enterococcus
Catheters
Staphylococcus aureus
Cross Infection
Uridine Diphosphate N-Acetylglucosamine
Catheter-Related Infections
Equipment and Supplies
Urinary Catheters
Indwelling Catheters
Uridine Diphosphate
Central Venous Catheters
Peptidoglycan
maleimide
Enzymes
Gram-Negative Bacteria
Cell Wall

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Suman, Ethel ; D'Souza, Sushma Janet ; Jacob, Pyari ; Sushruth, M. R. ; Kotian, M. Shashidhar. / Anti-biofilm and anti-adherence activity of Glm-U inhibitors. In: Indian Journal of Medical Sciences. 2011 ; Vol. 65, No. 9. pp. 387-392.
@article{5d2f65c3c62547f7a128b9d989f05e35,
title = "Anti-biofilm and anti-adherence activity of Glm-U inhibitors",
abstract = "Background: Intravascular catheters and urinary catheters are an important source of hospital-acquired infections. Many microorganisms colonize indwelling catheters, including central venous catheters (CVCs) forming biofilms and cause infections that are difficult to treat. Although various methods have been employed to reduce biofilms, enzymes involved in bacterial cell wall synthesis could provide novel targets for the development of anti-biofilm agents. N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and catalyzes the formation of uridine-diphospho-N- acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolysaccharide biosynthesis of Gram-positive and Gram-negative bacteria. Previous study has been conducted on the anti-biofilm effect of GlmU inhibitors such as N-ethyl maleimide (NEM) and NEM analogs along with a cationic polypeptide protamine sulfate (PS), which enhanced its anti-biofilm activity. AIM: The present study aimed at finding the effect of sub-inhibitory concentrations of N-ethyl maleimide (NEM) and protamine sulfate (PS) on the biofilms produced by Pseudomonas aeruginosa and Enterococcus spp. isolated from cases of catheter-associated UTI as well as Klebsiella pneumoniae and Staphylococcus aureus isolated from cases of catheter-related bloodstream infections (CRBSI). Materials and Methods: In order to enhance the activity of NEM and to develop a broad-spectrum anti-microbial composition, NEM (50 μg/ml) was combined with protamine sulfate (50 μg/ml) and tested for anti-biofilm activity using a standard quantitative biofilm assay method. Results and Conclusion: It was observed that NEM had no effect on the biofilm produced by Pseudomonas aeruginosa as well as by Enterococcus spp. NEM also caused a significant decrease in biofilm production by Staphylococcus aureus while it had no effect on the biofilm produced by Klebsiella pneumoniae. There was a significant synergistic inhibitory effect on Staphylococcus aureus and Enterococcus spp., whereas Pseudomonas aeruginosa and Klebsiella pneumoniae remained unaffected. Combination of GlmU inhibitor-plus-protamine sulfate failed to significantly reduce bacterial adherence of Pseudomonas aeruginosa and Klebsiella pneumoniae to catheter and cannula pieces, respectively. We found that the GlmU inhibitor was mainly effective in preventing the adherence and biofilm formation by gram-positive organisms. The combination of NEM and protamine sulfate may, therefore, be tried as anti-infective coatings for medical devices such as catheters and cannulas, and thus help in overcoming microbial resistance in the current era of increasing device-associated hospital infections.",
author = "Ethel Suman and D'Souza, {Sushma Janet} and Pyari Jacob and Sushruth, {M. R.} and Kotian, {M. Shashidhar}",
year = "2011",
month = "9",
day = "1",
doi = "10.4103/0019-5359.108954",
language = "English",
volume = "65",
pages = "387--392",
journal = "Indian Journal of Medical Sciences",
issn = "0019-5359",
publisher = "Medknow Publications and Media Pvt. Ltd",
number = "9",

}

Anti-biofilm and anti-adherence activity of Glm-U inhibitors. / Suman, Ethel; D'Souza, Sushma Janet; Jacob, Pyari; Sushruth, M. R.; Kotian, M. Shashidhar.

In: Indian Journal of Medical Sciences, Vol. 65, No. 9, 01.09.2011, p. 387-392.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-biofilm and anti-adherence activity of Glm-U inhibitors

AU - Suman, Ethel

AU - D'Souza, Sushma Janet

AU - Jacob, Pyari

AU - Sushruth, M. R.

AU - Kotian, M. Shashidhar

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Background: Intravascular catheters and urinary catheters are an important source of hospital-acquired infections. Many microorganisms colonize indwelling catheters, including central venous catheters (CVCs) forming biofilms and cause infections that are difficult to treat. Although various methods have been employed to reduce biofilms, enzymes involved in bacterial cell wall synthesis could provide novel targets for the development of anti-biofilm agents. N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and catalyzes the formation of uridine-diphospho-N- acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolysaccharide biosynthesis of Gram-positive and Gram-negative bacteria. Previous study has been conducted on the anti-biofilm effect of GlmU inhibitors such as N-ethyl maleimide (NEM) and NEM analogs along with a cationic polypeptide protamine sulfate (PS), which enhanced its anti-biofilm activity. AIM: The present study aimed at finding the effect of sub-inhibitory concentrations of N-ethyl maleimide (NEM) and protamine sulfate (PS) on the biofilms produced by Pseudomonas aeruginosa and Enterococcus spp. isolated from cases of catheter-associated UTI as well as Klebsiella pneumoniae and Staphylococcus aureus isolated from cases of catheter-related bloodstream infections (CRBSI). Materials and Methods: In order to enhance the activity of NEM and to develop a broad-spectrum anti-microbial composition, NEM (50 μg/ml) was combined with protamine sulfate (50 μg/ml) and tested for anti-biofilm activity using a standard quantitative biofilm assay method. Results and Conclusion: It was observed that NEM had no effect on the biofilm produced by Pseudomonas aeruginosa as well as by Enterococcus spp. NEM also caused a significant decrease in biofilm production by Staphylococcus aureus while it had no effect on the biofilm produced by Klebsiella pneumoniae. There was a significant synergistic inhibitory effect on Staphylococcus aureus and Enterococcus spp., whereas Pseudomonas aeruginosa and Klebsiella pneumoniae remained unaffected. Combination of GlmU inhibitor-plus-protamine sulfate failed to significantly reduce bacterial adherence of Pseudomonas aeruginosa and Klebsiella pneumoniae to catheter and cannula pieces, respectively. We found that the GlmU inhibitor was mainly effective in preventing the adherence and biofilm formation by gram-positive organisms. The combination of NEM and protamine sulfate may, therefore, be tried as anti-infective coatings for medical devices such as catheters and cannulas, and thus help in overcoming microbial resistance in the current era of increasing device-associated hospital infections.

AB - Background: Intravascular catheters and urinary catheters are an important source of hospital-acquired infections. Many microorganisms colonize indwelling catheters, including central venous catheters (CVCs) forming biofilms and cause infections that are difficult to treat. Although various methods have been employed to reduce biofilms, enzymes involved in bacterial cell wall synthesis could provide novel targets for the development of anti-biofilm agents. N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and catalyzes the formation of uridine-diphospho-N- acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolysaccharide biosynthesis of Gram-positive and Gram-negative bacteria. Previous study has been conducted on the anti-biofilm effect of GlmU inhibitors such as N-ethyl maleimide (NEM) and NEM analogs along with a cationic polypeptide protamine sulfate (PS), which enhanced its anti-biofilm activity. AIM: The present study aimed at finding the effect of sub-inhibitory concentrations of N-ethyl maleimide (NEM) and protamine sulfate (PS) on the biofilms produced by Pseudomonas aeruginosa and Enterococcus spp. isolated from cases of catheter-associated UTI as well as Klebsiella pneumoniae and Staphylococcus aureus isolated from cases of catheter-related bloodstream infections (CRBSI). Materials and Methods: In order to enhance the activity of NEM and to develop a broad-spectrum anti-microbial composition, NEM (50 μg/ml) was combined with protamine sulfate (50 μg/ml) and tested for anti-biofilm activity using a standard quantitative biofilm assay method. Results and Conclusion: It was observed that NEM had no effect on the biofilm produced by Pseudomonas aeruginosa as well as by Enterococcus spp. NEM also caused a significant decrease in biofilm production by Staphylococcus aureus while it had no effect on the biofilm produced by Klebsiella pneumoniae. There was a significant synergistic inhibitory effect on Staphylococcus aureus and Enterococcus spp., whereas Pseudomonas aeruginosa and Klebsiella pneumoniae remained unaffected. Combination of GlmU inhibitor-plus-protamine sulfate failed to significantly reduce bacterial adherence of Pseudomonas aeruginosa and Klebsiella pneumoniae to catheter and cannula pieces, respectively. We found that the GlmU inhibitor was mainly effective in preventing the adherence and biofilm formation by gram-positive organisms. The combination of NEM and protamine sulfate may, therefore, be tried as anti-infective coatings for medical devices such as catheters and cannulas, and thus help in overcoming microbial resistance in the current era of increasing device-associated hospital infections.

UR - http://www.scopus.com/inward/record.url?scp=84875461621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875461621&partnerID=8YFLogxK

U2 - 10.4103/0019-5359.108954

DO - 10.4103/0019-5359.108954

M3 - Article

C2 - 23508481

AN - SCOPUS:84875461621

VL - 65

SP - 387

EP - 392

JO - Indian Journal of Medical Sciences

JF - Indian Journal of Medical Sciences

SN - 0019-5359

IS - 9

ER -