Novel Group of Leaderless Multipeptide Bacteriocins from Gram-Positive Bacteria

Ovchinnikov, Kirill V.; Chi, Hai; Mehmeti, Ibrahim; Holo, Helge; Nes, Ingolf F.; Diep, Dzung B.

doi:10.1128/aem.01094-16

Cited by 80 publications

(96 citation statements)

References 39 publications

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“…We have previously shown that synthetic GarKS is functionally comparable to the biologically produced counterpart (31). Synthetic GarKS (with > 90% purity) has a specific activity of 130-140 BU/µg.…”

Section: Resultsmentioning

confidence: 93%

“…It is well known that bacteria are ecologically adapted to the environments where they normally thrive. Since the producer KS1546 was isolated from raw milk (31), we examine the possibility to use skim milk (SM) as growth medium. Bacteriocin production was increased 2-fold in SM (160 BU/ml) compared to GM17 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…GarKS is potent against a set of important pathogens including Staphylococcus , Bacillus , Listeria, Streptococcus and Enterococcus , making it very attractive in diverse antimicrobial applications from food to medicine. Unfortunately, as also for many other bacteriocins, GarKS is produced at relatively low levels during normal laboratory growth conditions (31). The low production by the native producer can dramatically hamper potential applications of GarKS as industrial use of bacteriocins requires high and cost-effective production.…”

Section: Discussionmentioning

confidence: 99%

“…Recently we have reported the identification and characterization of a novel three-peptide bacteriocin called garvicin KS (GarKS), produced by L. garvieae KS1546, a strain isolated from raw bovine milk in Kosovo (31). A gene cluster ( gak ) containing the three structural genes ( gakABC ) and genes likely involved in immunity ( gakIR ) and transport ( gakT ) has been identified in the genome (31). GarKS is active against a broad spectrum of bacteria such as Listeria, Staphylococcus , Bacillus , Streptococcus and Enterococcus (31).…”

Section: Introductionmentioning

confidence: 99%

“…A gene cluster ( gak ) containing the three structural genes ( gakABC ) and genes likely involved in immunity ( gakIR ) and transport ( gakT ) has been identified in the genome (31). GarKS is active against a broad spectrum of bacteria such as Listeria, Staphylococcus , Bacillus , Streptococcus and Enterococcus (31). Despite its great potential, production of GarKS is relatively moderate in standard laboratory growth conditions.…”

Section: Introductionmentioning

confidence: 99%

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Over 2000-fold increased production of the leaderless bacteriocin garvicin KS by genetic engineering and optimization of culture conditions

Telke

et al. 2018

Preprint

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20The leaderless bacteriocin Garvicin KS (GarKS) is a potent antimicrobial, being active against a 21 wide range of important pathogens. GarKS production by the native producer Lactococcus 22 garvieae KS1546 was however relatively low (80 BU/ml) under standard laboratory growth 23 conditions (batch culture in GM17 at 30°C). To improve the production of GarKS, we 24 systematically evaluated the impact of different media and media components on bacteriocin 25 production. Based on the outcomes a new medium formulation was made to greatly improve 26 bacteriocin production. The new medium composed of pasteurized milk and tryptone (PM-T), 27increased GarKS production about 60-fold compared to that achieved in GM17. GarKS production 28 was increased further 4-fold (i.e., to 20,000 BU/ml) by increasing gene dose of the bacteriocin 29 gene cluster (gak) in the native producer. Finally, a combination of the newly composed medium 30 (PM-T), an increased gene dose and a cultivation at a constant pH 6 and a 50-60% dissolved 31 oxygen level in growth medium, gave rise to a GarKS production of 164,000 BU/ml. This high 32 production, which is about 2000-fold higher compared to that initially achieved in GM17, 33 corresponds to a GarKS production of 1.2 g/L. To our knowledge, this is one of the highest 34 bacteriocin production reported hitherto. 35Importance: Low bacteriocin production is a well-known bottle-neck in developing bacteriocins 36 into large-scaled and useful applications. The present study shows different approaches that 37 significantly improve bacteriocin production. This is an important research field to better exploit 38 the antimicrobial potential of bacteriocins, especially with regard to the decreasing effect of 39 antibiotics in infection treatments due to the global emergence of antibiotic resistance. 40 41 42The decreasing effectiveness of antibiotics has become a serious worldwide problem due to the 43 emergence of multidrug-resistant bacteria (1, 2). Despite that, the number of new commercially 44 available antibiotics is dwindling. This is partly due to the fact that developing new antibiotics is 45 a very costly process (3), and the biopharma companies are therefore often reluctant to invest large 46 money in new antibiotics that soon may be useless because of resistance development. 47Consequently, there is an urgent need of cost-effective and efficient antimicrobial agents with 48 different killing mechanisms to overcome multidrug-resistant bacteria. 49Bacteriocins are ribosomally synthesized antibacterial peptides produced by bacteria, probably as 50 a means to compete for nutrients and habitats (4). So far hundreds of bacteriocins have been 51 isolated and characterized. Most of them have narrow-spectrum activity but some are active 52 against a broad-spectrum of bacteria including food-spoiling bacteria as well as important 53 pathogens (5, 6). Bacteriocins produced by lactic acid bacteria (LAB) are particularly interesting 54 due to LAB's safe status as they are commonly found in our foods (7, 8)...

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%