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A bioengineered nisin derivative to control biofilms of Staphylococcus pseudintermedius.

Field D, Gaudin N, Lyons F, O'Connor PM, Cotter PD, Hill C, Ross RP - PLoS ONE (2015)

Bottom Line: In this study we created a nisin derivative with enhanced antimicrobial activity against S. pseudintermedius.In addition, the novel nisin derivative exhibits an enhanced ability to impair biofilm formation and to reduce the density of established biofilms.The activities of this peptide represent a significant improvement over that of the wild-type nisin peptide and merit further investigation with a view to their use to treat S. pseudintermedius infections.

View Article: PubMed Central - PubMed

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

ABSTRACT
Antibiotic resistance and the shortage of novel antimicrobials are among the biggest challenges facing society. One of the major factors contributing to resistance is the use of frontline clinical antibiotics in veterinary practice. In order to properly manage dwindling antibiotic resources, we must identify antimicrobials that are specifically targeted to veterinary applications. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many gram-positive bacteria, including human and animal pathogens such as Staphylococcus, Bacillus, Listeria, and Clostridium. Although not currently used in human medicine, nisin is already employed commercially as an anti-mastitis product in the veterinary field. 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 (MRSA) and vancomycin-resistant enterococci (VRE) and also against staphylococci and streptococci associated with bovine mastitis. However, newly emerging pathogens such as methicillin resistant Staphylococcus pseudintermedius (MRSP) pose a significant threat in terms of veterinary health and as a reservoir for antibiotic resistance determinants. In this study we created a nisin derivative with enhanced antimicrobial activity against S. pseudintermedius. In addition, the novel nisin derivative exhibits an enhanced ability to impair biofilm formation and to reduce the density of established biofilms. The activities of this peptide represent a significant improvement over that of the wild-type nisin peptide and merit further investigation with a view to their use to treat S. pseudintermedius infections.

No MeSH data available.


Related in: MedlinePlus

Structure of nisin A and deferred antagonism assays of nisin A and nisin I4V.(A) Residues are represented in the single letter code. Post translational modifications are indicated as follows, Dha: dehydroalanine, Dhb: dehydrobutyrine, Abu: 2-aminobutyric acid, A-A: lanthionine, Abu-A: 3-methyllanthionine. (B) Growth inhibition of S. intermedius DSM 20373, S. pseudintermedius DK729 and S. pseudintermedius DSM21284 by the nisin A producing strain L. lactis NZ9800 pDF05 (pCI372-nisA) and the nisin derivative I4V producing strain L. lactis NZ9800 pDF12 (nisA-I4V).
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pone.0119684.g001: Structure of nisin A and deferred antagonism assays of nisin A and nisin I4V.(A) Residues are represented in the single letter code. Post translational modifications are indicated as follows, Dha: dehydroalanine, Dhb: dehydrobutyrine, Abu: 2-aminobutyric acid, A-A: lanthionine, Abu-A: 3-methyllanthionine. (B) Growth inhibition of S. intermedius DSM 20373, S. pseudintermedius DK729 and S. pseudintermedius DSM21284 by the nisin A producing strain L. lactis NZ9800 pDF05 (pCI372-nisA) and the nisin derivative I4V producing strain L. lactis NZ9800 pDF12 (nisA-I4V).

Mentions: The diminished capacity of currently available antibiotics to control pathogenic bacteria is a major cause for concern. Against this backdrop, methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged over the last decade as a critically important, opportunistic canine pathogen responsible for skin, soft tissue, and surgical site infections [1]. Although frequently detected in dogs, MRSP has also been isolated from several other host species including cats, horses, donkeys and birds [2]. Worryingly, MRSP has implications for public health as transmission between humans and their pets can occur via direct and indirect contact and infections in humans have been described [3]. MRSP can form biofilms [4,5]; complex, sessile communities of bacteria embedded in an organic polymer matrix [6]. Biofilm formation is now recognized as an important virulence factor in several Staphylococcus spp. [7], providing the bacteria with chemical and physical protection from the host immune response and the effects of antimicrobials [8]. In addition to methicillin resistance and biofilm formation, the acquisition of other resistance genes and resistance-mediating mutations in some MRSP isolates renders these strains resistant to the majority of antimicrobial agents utilized in veterinary medicine [9]. MRSP isolates are typically resistant to aminoglycosides, fluoroquinolones, macrolides, lincosamides, trimethoprim sulfamethoxazol and, in many cases, to tetracycline and chloramphenicol [9–11]. Thus new alternatives to conventional antibiotic therapies are urgently needed. One group of compounds with enormous potential for therapeutic use is the lantibiotic class of bacteriocins (bacterially derived antimicrobial peptides) [12,13]. Lantibiotics are gene-encoded, ribosomally-synthesized peptides that are characterised by the presence of unusual amino acids including lanthionine and/or methyllanthionine [14–16]. The most intensively studied lantibiotic is nisin (Fig. 1A). Produced by Lactococcus lactis, nisin exhibits antibacterial activity against a wide range of Gram-positive bacteria, including foodborne pathogens such as staphylococci, bacilli and clostridia. Nisin is used as a food preservative in over 50 countries and has been approved in the EU (as additive E234) and by the US Food and Drug Administration (FDA) [17]. In addition, both nisin A (and its natural variant nisin Z) are effective against the Gram positive pathogens responsible for bovine mastitis and have been incorporated into a number of products (such as Wipe Out and Mast Out) dedicated to controlling or treating such infections [12,18–20]. Additionally, Bayer have recently released Preva medicated wipes containing 25μg/ml nisin for topical use on dogs, cats, and horses with dermatological conditions associated with bacterial infections or general cleansing (www.animalhealth.bayerhealthcare.com). Notably, in addition to being effective against planktonic cells of multi-drug resistant staphylococci [21,22], nisin has also demonstrated efficacy against biofilms [22–24]. This activity can be further enhanced by taking advantage of the fact that nisin functions synergistically with several conventional antibiotics against biofilms of MRSA [25].


A bioengineered nisin derivative to control biofilms of Staphylococcus pseudintermedius.

Field D, Gaudin N, Lyons F, O'Connor PM, Cotter PD, Hill C, Ross RP - PLoS ONE (2015)

Structure of nisin A and deferred antagonism assays of nisin A and nisin I4V.(A) Residues are represented in the single letter code. Post translational modifications are indicated as follows, Dha: dehydroalanine, Dhb: dehydrobutyrine, Abu: 2-aminobutyric acid, A-A: lanthionine, Abu-A: 3-methyllanthionine. (B) Growth inhibition of S. intermedius DSM 20373, S. pseudintermedius DK729 and S. pseudintermedius DSM21284 by the nisin A producing strain L. lactis NZ9800 pDF05 (pCI372-nisA) and the nisin derivative I4V producing strain L. lactis NZ9800 pDF12 (nisA-I4V).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4366236&req=5

pone.0119684.g001: Structure of nisin A and deferred antagonism assays of nisin A and nisin I4V.(A) Residues are represented in the single letter code. Post translational modifications are indicated as follows, Dha: dehydroalanine, Dhb: dehydrobutyrine, Abu: 2-aminobutyric acid, A-A: lanthionine, Abu-A: 3-methyllanthionine. (B) Growth inhibition of S. intermedius DSM 20373, S. pseudintermedius DK729 and S. pseudintermedius DSM21284 by the nisin A producing strain L. lactis NZ9800 pDF05 (pCI372-nisA) and the nisin derivative I4V producing strain L. lactis NZ9800 pDF12 (nisA-I4V).
Mentions: The diminished capacity of currently available antibiotics to control pathogenic bacteria is a major cause for concern. Against this backdrop, methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged over the last decade as a critically important, opportunistic canine pathogen responsible for skin, soft tissue, and surgical site infections [1]. Although frequently detected in dogs, MRSP has also been isolated from several other host species including cats, horses, donkeys and birds [2]. Worryingly, MRSP has implications for public health as transmission between humans and their pets can occur via direct and indirect contact and infections in humans have been described [3]. MRSP can form biofilms [4,5]; complex, sessile communities of bacteria embedded in an organic polymer matrix [6]. Biofilm formation is now recognized as an important virulence factor in several Staphylococcus spp. [7], providing the bacteria with chemical and physical protection from the host immune response and the effects of antimicrobials [8]. In addition to methicillin resistance and biofilm formation, the acquisition of other resistance genes and resistance-mediating mutations in some MRSP isolates renders these strains resistant to the majority of antimicrobial agents utilized in veterinary medicine [9]. MRSP isolates are typically resistant to aminoglycosides, fluoroquinolones, macrolides, lincosamides, trimethoprim sulfamethoxazol and, in many cases, to tetracycline and chloramphenicol [9–11]. Thus new alternatives to conventional antibiotic therapies are urgently needed. One group of compounds with enormous potential for therapeutic use is the lantibiotic class of bacteriocins (bacterially derived antimicrobial peptides) [12,13]. Lantibiotics are gene-encoded, ribosomally-synthesized peptides that are characterised by the presence of unusual amino acids including lanthionine and/or methyllanthionine [14–16]. The most intensively studied lantibiotic is nisin (Fig. 1A). Produced by Lactococcus lactis, nisin exhibits antibacterial activity against a wide range of Gram-positive bacteria, including foodborne pathogens such as staphylococci, bacilli and clostridia. Nisin is used as a food preservative in over 50 countries and has been approved in the EU (as additive E234) and by the US Food and Drug Administration (FDA) [17]. In addition, both nisin A (and its natural variant nisin Z) are effective against the Gram positive pathogens responsible for bovine mastitis and have been incorporated into a number of products (such as Wipe Out and Mast Out) dedicated to controlling or treating such infections [12,18–20]. Additionally, Bayer have recently released Preva medicated wipes containing 25μg/ml nisin for topical use on dogs, cats, and horses with dermatological conditions associated with bacterial infections or general cleansing (www.animalhealth.bayerhealthcare.com). Notably, in addition to being effective against planktonic cells of multi-drug resistant staphylococci [21,22], nisin has also demonstrated efficacy against biofilms [22–24]. This activity can be further enhanced by taking advantage of the fact that nisin functions synergistically with several conventional antibiotics against biofilms of MRSA [25].

Bottom Line: In this study we created a nisin derivative with enhanced antimicrobial activity against S. pseudintermedius.In addition, the novel nisin derivative exhibits an enhanced ability to impair biofilm formation and to reduce the density of established biofilms.The activities of this peptide represent a significant improvement over that of the wild-type nisin peptide and merit further investigation with a view to their use to treat S. pseudintermedius infections.

View Article: PubMed Central - PubMed

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

ABSTRACT
Antibiotic resistance and the shortage of novel antimicrobials are among the biggest challenges facing society. One of the major factors contributing to resistance is the use of frontline clinical antibiotics in veterinary practice. In order to properly manage dwindling antibiotic resources, we must identify antimicrobials that are specifically targeted to veterinary applications. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many gram-positive bacteria, including human and animal pathogens such as Staphylococcus, Bacillus, Listeria, and Clostridium. Although not currently used in human medicine, nisin is already employed commercially as an anti-mastitis product in the veterinary field. 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 (MRSA) and vancomycin-resistant enterococci (VRE) and also against staphylococci and streptococci associated with bovine mastitis. However, newly emerging pathogens such as methicillin resistant Staphylococcus pseudintermedius (MRSP) pose a significant threat in terms of veterinary health and as a reservoir for antibiotic resistance determinants. In this study we created a nisin derivative with enhanced antimicrobial activity against S. pseudintermedius. In addition, the novel nisin derivative exhibits an enhanced ability to impair biofilm formation and to reduce the density of established biofilms. The activities of this peptide represent a significant improvement over that of the wild-type nisin peptide and merit further investigation with a view to their use to treat S. pseudintermedius infections.

No MeSH data available.


Related in: MedlinePlus