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Chitosan coupling makes microbial biofilms susceptible to antibiotics.

Zhang A, Mu H, Zhang W, Cui G, Zhu J, Duan J - Sci Rep (2013)

Bottom Line: Microbial biofilms, prevalent in nature and inherently resistant to both antimicrobial agents and host defenses, can cause serious problems in the chemical, medical and pharmaceutical industries.Herein we demonstrated that conjugation of an aminoglycoside antibiotic (streptomycin) to chitosan could efficiently damage established biofilms and inhibit biofilm formation.This method was suitable to eradiate biofilms formed by Gram-positive organisms, and it appeared that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this anti-biofilm activity.

View Article: PubMed Central - PubMed

Affiliation: 1] College of science, Northwest A&F University, Yangling 712100, Shaanxi, China [2].

ABSTRACT
Microbial biofilms, prevalent in nature and inherently resistant to both antimicrobial agents and host defenses, can cause serious problems in the chemical, medical and pharmaceutical industries. Herein we demonstrated that conjugation of an aminoglycoside antibiotic (streptomycin) to chitosan could efficiently damage established biofilms and inhibit biofilm formation. This method was suitable to eradiate biofilms formed by Gram-positive organisms, and it appeared that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this anti-biofilm activity. Mechanistic insight demonstrated chitosan conjugation rendered streptomycin more accessible into biofilms, thereby available to interact with biofilm bacteria. Thus, this work represent an innovative strategy that antibiotic covalently linked to carbohydrate carriers can overcome antibiotic resistance of microbial biofilms, and might provide a comprehensive solution to combat biofilms in industrial and medical settings.

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Related in: MedlinePlus

Structure-activity relationships in anti-biofilm capacities of C − S conjugate.(A–C) L. monocytogenes biofilms were exposed to the following conjugates (C − S) and the respective mixtures (C + S) at 0.25 mg/mL for 24 h. Biofilms incubated in TSB containing phosphate-buffered saline were used as control. Biofilm mass and viable cells were quantified. (A) ~13 k chitosan derived C − S conjugates containing 0.3%, 15%, 23% and 32% (w/w) streptomycin; (B) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan with different molecular mass: ~3 k (streptomycin: 30%), ~13 k (streptomycin: 28%) and ~180 k Da (streptomycin: 30%); (C) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan (~13 k Da) with different N-deacetylation degrees: 50% DD (streptomycin: 25%), 75% DD (streptomycin: 23%) and 88% DD (streptomycin: 26%); (D) L. monocytogenes biofilms were exposed to 0.25 mg/mL of L-S conjugate containing 42% streptomycin, equivalent epoly-L-lysine (L, 2 ~ 3 kDa) or streptomycin (S) alone, and the respective mixture (L + S) for 24 h. These experiments were performed three times with similar results each time. Error bars represent SD.
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f3: Structure-activity relationships in anti-biofilm capacities of C − S conjugate.(A–C) L. monocytogenes biofilms were exposed to the following conjugates (C − S) and the respective mixtures (C + S) at 0.25 mg/mL for 24 h. Biofilms incubated in TSB containing phosphate-buffered saline were used as control. Biofilm mass and viable cells were quantified. (A) ~13 k chitosan derived C − S conjugates containing 0.3%, 15%, 23% and 32% (w/w) streptomycin; (B) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan with different molecular mass: ~3 k (streptomycin: 30%), ~13 k (streptomycin: 28%) and ~180 k Da (streptomycin: 30%); (C) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan (~13 k Da) with different N-deacetylation degrees: 50% DD (streptomycin: 25%), 75% DD (streptomycin: 23%) and 88% DD (streptomycin: 26%); (D) L. monocytogenes biofilms were exposed to 0.25 mg/mL of L-S conjugate containing 42% streptomycin, equivalent epoly-L-lysine (L, 2 ~ 3 kDa) or streptomycin (S) alone, and the respective mixture (L + S) for 24 h. These experiments were performed three times with similar results each time. Error bars represent SD.

Mentions: To clarify the role of streptomycin contents in anti-biofilm capacity of C − S conjugates, various amounts of streptomycin [0.3%, 15%, 23%, 32% (w/w)] were coupled to chitosan with a molecular mass of ~13 kDa. It appeared that the C − S conjugate containing 0.3% (w/w) streptomycin was not sufficient for induction of higher anti-biofilm and bactericidal activities than the mixture did (Figure 3A). An increase in streptomycin contents significantly enhanced the anti-biofilm and bactericidal capacity of C − S conjugates. Particularly, the C − S conjugate containing 23% streptomycin displayed an optimal activity for biofilm disruption and cell killing towards L. monocytogenes.


Chitosan coupling makes microbial biofilms susceptible to antibiotics.

Zhang A, Mu H, Zhang W, Cui G, Zhu J, Duan J - Sci Rep (2013)

Structure-activity relationships in anti-biofilm capacities of C − S conjugate.(A–C) L. monocytogenes biofilms were exposed to the following conjugates (C − S) and the respective mixtures (C + S) at 0.25 mg/mL for 24 h. Biofilms incubated in TSB containing phosphate-buffered saline were used as control. Biofilm mass and viable cells were quantified. (A) ~13 k chitosan derived C − S conjugates containing 0.3%, 15%, 23% and 32% (w/w) streptomycin; (B) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan with different molecular mass: ~3 k (streptomycin: 30%), ~13 k (streptomycin: 28%) and ~180 k Da (streptomycin: 30%); (C) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan (~13 k Da) with different N-deacetylation degrees: 50% DD (streptomycin: 25%), 75% DD (streptomycin: 23%) and 88% DD (streptomycin: 26%); (D) L. monocytogenes biofilms were exposed to 0.25 mg/mL of L-S conjugate containing 42% streptomycin, equivalent epoly-L-lysine (L, 2 ~ 3 kDa) or streptomycin (S) alone, and the respective mixture (L + S) for 24 h. These experiments were performed three times with similar results each time. Error bars represent SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f3: Structure-activity relationships in anti-biofilm capacities of C − S conjugate.(A–C) L. monocytogenes biofilms were exposed to the following conjugates (C − S) and the respective mixtures (C + S) at 0.25 mg/mL for 24 h. Biofilms incubated in TSB containing phosphate-buffered saline were used as control. Biofilm mass and viable cells were quantified. (A) ~13 k chitosan derived C − S conjugates containing 0.3%, 15%, 23% and 32% (w/w) streptomycin; (B) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan with different molecular mass: ~3 k (streptomycin: 30%), ~13 k (streptomycin: 28%) and ~180 k Da (streptomycin: 30%); (C) C − S conjugates which contain similar levels of streptomycin and were derived from chitosan (~13 k Da) with different N-deacetylation degrees: 50% DD (streptomycin: 25%), 75% DD (streptomycin: 23%) and 88% DD (streptomycin: 26%); (D) L. monocytogenes biofilms were exposed to 0.25 mg/mL of L-S conjugate containing 42% streptomycin, equivalent epoly-L-lysine (L, 2 ~ 3 kDa) or streptomycin (S) alone, and the respective mixture (L + S) for 24 h. These experiments were performed three times with similar results each time. Error bars represent SD.
Mentions: To clarify the role of streptomycin contents in anti-biofilm capacity of C − S conjugates, various amounts of streptomycin [0.3%, 15%, 23%, 32% (w/w)] were coupled to chitosan with a molecular mass of ~13 kDa. It appeared that the C − S conjugate containing 0.3% (w/w) streptomycin was not sufficient for induction of higher anti-biofilm and bactericidal activities than the mixture did (Figure 3A). An increase in streptomycin contents significantly enhanced the anti-biofilm and bactericidal capacity of C − S conjugates. Particularly, the C − S conjugate containing 23% streptomycin displayed an optimal activity for biofilm disruption and cell killing towards L. monocytogenes.

Bottom Line: Microbial biofilms, prevalent in nature and inherently resistant to both antimicrobial agents and host defenses, can cause serious problems in the chemical, medical and pharmaceutical industries.Herein we demonstrated that conjugation of an aminoglycoside antibiotic (streptomycin) to chitosan could efficiently damage established biofilms and inhibit biofilm formation.This method was suitable to eradiate biofilms formed by Gram-positive organisms, and it appeared that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this anti-biofilm activity.

View Article: PubMed Central - PubMed

Affiliation: 1] College of science, Northwest A&F University, Yangling 712100, Shaanxi, China [2].

ABSTRACT
Microbial biofilms, prevalent in nature and inherently resistant to both antimicrobial agents and host defenses, can cause serious problems in the chemical, medical and pharmaceutical industries. Herein we demonstrated that conjugation of an aminoglycoside antibiotic (streptomycin) to chitosan could efficiently damage established biofilms and inhibit biofilm formation. This method was suitable to eradiate biofilms formed by Gram-positive organisms, and it appeared that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this anti-biofilm activity. Mechanistic insight demonstrated chitosan conjugation rendered streptomycin more accessible into biofilms, thereby available to interact with biofilm bacteria. Thus, this work represent an innovative strategy that antibiotic covalently linked to carbohydrate carriers can overcome antibiotic resistance of microbial biofilms, and might provide a comprehensive solution to combat biofilms in industrial and medical settings.

Show MeSH
Related in: MedlinePlus