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In Vitro Activities of Nisin and Nisin Derivatives Alone and In Combination with Antibiotics against Staphylococcus Biofilms.

Field D, O' Connor R, Cotter PD, Ross RP, Hill C - Front Microbiol (2016)

Bottom Line: Growth curve-based comparisons established that combinations of derivatives nisin V + penicillin or nisin I4V + chloramphenicol had an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius DSM21284, respectively, compared to the equivalent nisin A + antibiotic combinations or when each antimicrobial was administered alone.Furthermore, the metabolic activity of established biofilms treated with nisin V + chloramphenicol and nisin I4V + chloramphenicol combinations revealed a significant decrease in S. aureus SA113 and S. pseudintermedius DSM21284 biofilm viability, respectively, compared to the nisin A + antibiotic combinations as determined by the rapid colorimetric XTT assay.The results indicate that the activities of the nisin derivative and antibiotic combinations represent a significant improvement over that of the wild-type nisin and antibiotic combination and merit further investigation with a view to their use as anti-biofilm agents.

View Article: PubMed Central - PubMed

Affiliation: School of Microbiology, University College Cork Cork, Ireland.

ABSTRACT
The development and spread of pathogenic bacteria that are resistant to the existing catalog of antibiotics is a major public health threat. Biofilms are complex, sessile communities of bacteria embedded in an organic polymer matrix which serve to further enhance antimicrobial resistance. Consequently, novel compounds and innovative methods are urgently required to arrest the proliferation of drug-resistant infections in both nosocomial and community environments. Accordingly, it has been suggested that antimicrobial peptides could be used as novel natural inhibitors that can be used in formulations with synergistically acting antibiotics. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many Gram-positive bacteria. Recently we have used bioengineering strategies to enhance the activity of nisin against several high profile targets, including multi-drug resistant clinical pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, staphylococci, and streptococci associated with bovine mastitis. We have also identified nisin derivatives with an enhanced ability to impair biofilm formation and to reduce the density of established biofilms of methicillin resistant S. pseudintermedius. The present study was aimed at evaluating the potential of nisin and nisin derivatives to increase the efficacy of conventional antibiotics and to assess the possibility of killing and/or eradicating biofilm-associated cells of a variety of staphylococcal targets. Growth curve-based comparisons established that combinations of derivatives nisin V + penicillin or nisin I4V + chloramphenicol had an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius DSM21284, respectively, compared to the equivalent nisin A + antibiotic combinations or when each antimicrobial was administered alone. Furthermore, the metabolic activity of established biofilms treated with nisin V + chloramphenicol and nisin I4V + chloramphenicol combinations revealed a significant decrease in S. aureus SA113 and S. pseudintermedius DSM21284 biofilm viability, respectively, compared to the nisin A + antibiotic combinations as determined by the rapid colorimetric XTT assay. The results indicate that the activities of the nisin derivative and antibiotic combinations represent a significant improvement over that of the wild-type nisin and antibiotic combination and merit further investigation with a view to their use as anti-biofilm agents.

No MeSH data available.


Related in: MedlinePlus

Growth curve analysis of S. pseudintermedius DSM21284 in the presence of nisin A (A), nisin V (V), and nisin I4V (I4V) peptides (0.292 μM; 0.932 μg/ml) and in combination with 0.8 μg/ml penicillin (Pen), 3.0 μg/ml chloramphenicol (Cm), 0.5 μg/ml vancomycin (Van), and 4.0 μg/ml erythromycin (Ery). The means and standard deviations of three independent determinations are presented.
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Figure 2: Growth curve analysis of S. pseudintermedius DSM21284 in the presence of nisin A (A), nisin V (V), and nisin I4V (I4V) peptides (0.292 μM; 0.932 μg/ml) and in combination with 0.8 μg/ml penicillin (Pen), 3.0 μg/ml chloramphenicol (Cm), 0.5 μg/ml vancomycin (Van), and 4.0 μg/ml erythromycin (Ery). The means and standard deviations of three independent determinations are presented.

Mentions: When S. pseudintermedius DSM 21284 was employed, nisin A caused a slight delay in growth relative to the non nisin-containing control at the concentration of peptide used (0.2 μM; 0.6 μg/ml) (Figure 2A). Identical concentrations of nisin I4V resulted in a greatly extended lag time, highlighting its greater potency as previously observed (Field et al., 2015b). Furthermore, when combined with penicillin (0.8 μg/ml), the nisin I4V + penicillin combination appeared to completely inhibit the growth of S. pseudintermedius DSM 21284. This impact was not apparent for any other combination of nisin or nisin variant (M21V) and penicillin or when any antimicrobial compound was used alone (Figure 2A). Indeed, the benefits of employing I4V were evident when combinations of nisin and nisin derivatives with chloramphenicol (Figure 2B), vancomycin (Figure 2C), and erythromycin (Figure 2D) were used in that the longest lag in growth was observed for the nisin I4V and antibiotic combination compared to all others tested.


In Vitro Activities of Nisin and Nisin Derivatives Alone and In Combination with Antibiotics against Staphylococcus Biofilms.

Field D, O' Connor R, Cotter PD, Ross RP, Hill C - Front Microbiol (2016)

Growth curve analysis of S. pseudintermedius DSM21284 in the presence of nisin A (A), nisin V (V), and nisin I4V (I4V) peptides (0.292 μM; 0.932 μg/ml) and in combination with 0.8 μg/ml penicillin (Pen), 3.0 μg/ml chloramphenicol (Cm), 0.5 μg/ml vancomycin (Van), and 4.0 μg/ml erythromycin (Ery). The means and standard deviations of three independent determinations are presented.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834297&req=5

Figure 2: Growth curve analysis of S. pseudintermedius DSM21284 in the presence of nisin A (A), nisin V (V), and nisin I4V (I4V) peptides (0.292 μM; 0.932 μg/ml) and in combination with 0.8 μg/ml penicillin (Pen), 3.0 μg/ml chloramphenicol (Cm), 0.5 μg/ml vancomycin (Van), and 4.0 μg/ml erythromycin (Ery). The means and standard deviations of three independent determinations are presented.
Mentions: When S. pseudintermedius DSM 21284 was employed, nisin A caused a slight delay in growth relative to the non nisin-containing control at the concentration of peptide used (0.2 μM; 0.6 μg/ml) (Figure 2A). Identical concentrations of nisin I4V resulted in a greatly extended lag time, highlighting its greater potency as previously observed (Field et al., 2015b). Furthermore, when combined with penicillin (0.8 μg/ml), the nisin I4V + penicillin combination appeared to completely inhibit the growth of S. pseudintermedius DSM 21284. This impact was not apparent for any other combination of nisin or nisin variant (M21V) and penicillin or when any antimicrobial compound was used alone (Figure 2A). Indeed, the benefits of employing I4V were evident when combinations of nisin and nisin derivatives with chloramphenicol (Figure 2B), vancomycin (Figure 2C), and erythromycin (Figure 2D) were used in that the longest lag in growth was observed for the nisin I4V and antibiotic combination compared to all others tested.

Bottom Line: Growth curve-based comparisons established that combinations of derivatives nisin V + penicillin or nisin I4V + chloramphenicol had an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius DSM21284, respectively, compared to the equivalent nisin A + antibiotic combinations or when each antimicrobial was administered alone.Furthermore, the metabolic activity of established biofilms treated with nisin V + chloramphenicol and nisin I4V + chloramphenicol combinations revealed a significant decrease in S. aureus SA113 and S. pseudintermedius DSM21284 biofilm viability, respectively, compared to the nisin A + antibiotic combinations as determined by the rapid colorimetric XTT assay.The results indicate that the activities of the nisin derivative and antibiotic combinations represent a significant improvement over that of the wild-type nisin and antibiotic combination and merit further investigation with a view to their use as anti-biofilm agents.

View Article: PubMed Central - PubMed

Affiliation: School of Microbiology, University College Cork Cork, Ireland.

ABSTRACT
The development and spread of pathogenic bacteria that are resistant to the existing catalog of antibiotics is a major public health threat. Biofilms are complex, sessile communities of bacteria embedded in an organic polymer matrix which serve to further enhance antimicrobial resistance. Consequently, novel compounds and innovative methods are urgently required to arrest the proliferation of drug-resistant infections in both nosocomial and community environments. Accordingly, it has been suggested that antimicrobial peptides could be used as novel natural inhibitors that can be used in formulations with synergistically acting antibiotics. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many Gram-positive bacteria. Recently we have used bioengineering strategies to enhance the activity of nisin against several high profile targets, including multi-drug resistant clinical pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, staphylococci, and streptococci associated with bovine mastitis. We have also identified nisin derivatives with an enhanced ability to impair biofilm formation and to reduce the density of established biofilms of methicillin resistant S. pseudintermedius. The present study was aimed at evaluating the potential of nisin and nisin derivatives to increase the efficacy of conventional antibiotics and to assess the possibility of killing and/or eradicating biofilm-associated cells of a variety of staphylococcal targets. Growth curve-based comparisons established that combinations of derivatives nisin V + penicillin or nisin I4V + chloramphenicol had an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius DSM21284, respectively, compared to the equivalent nisin A + antibiotic combinations or when each antimicrobial was administered alone. Furthermore, the metabolic activity of established biofilms treated with nisin V + chloramphenicol and nisin I4V + chloramphenicol combinations revealed a significant decrease in S. aureus SA113 and S. pseudintermedius DSM21284 biofilm viability, respectively, compared to the nisin A + antibiotic combinations as determined by the rapid colorimetric XTT assay. The results indicate that the activities of the nisin derivative and antibiotic combinations represent a significant improvement over that of the wild-type nisin and antibiotic combination and merit further investigation with a view to their use as anti-biofilm agents.

No MeSH data available.


Related in: MedlinePlus