Nisin Z, Mutant Nisin Z and Lacticin 481 Interactions with Anionic Lipids Correlate with Antimicrobial Activity. A Monolayer Study

ABSTRACT The only human cathelicidin, the 37-residue peptide LL-37, exhibits antimicrobial activity against both gram-positive and gram-negative bacteria. We studied the ability of several fragments of LL-37, exhibiting different antimicrobial activities, to interact with membranes whose compositions mimic the cytoplasmic membranes of gram-positive or of gram-negative bacteria. These fragments are as follows: KR-12, the smallest active segment of LL-37, with the sequence KRIVQRIKDFLR, which exhibits antimicrobial activity only against gram-negative bacteria; a slightly smaller peptide, RI-10, missing the two cationic residues at the N and C termini of KR-12, which has been shown not to have any antimicrobial activity; a longer peptide, GF-17, which shows antimicrobial activity against gram-positive as well as gram-negative bacteria; and GF-17D3, with 3 d-amino-acid residues, which is also selective only for gram-negative bacteria. Those fragments with the capacity to cluster anionic lipids away from zwitterionic lipids in a membrane exhibit selective toxicity toward bacteria containing zwitterionic as well as anionic lipids in their cytoplasmic membranes but not toward bacteria with only anionic lipids. This finding allows for the prediction of the bacterial-species selectivity of certain agents and paves the way for designing new antimicrobials targeted specifically toward gram-negative bacteria.

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Influence of Ca2+ Ions on the Activity of Lantibiotics Containing a Mersacidin-Like Lipid II Binding Motif

Applied and Environmental Microbiology ◽

10.1128/aem.00262-09 ◽

2009 ◽

Vol 75 (13) ◽

pp. 4427-4434 ◽

Cited By ~ 23

Author(s):

T. Böttiger ◽

T. Schneider ◽

B. Martínez ◽

H.-G. Sahl ◽

I. Wiedemann

Keyword(s):

Antimicrobial Activity ◽

Cell Wall ◽

Mode Of Action ◽

Cell Wall Biosynthesis ◽

Binding Motif ◽

Bacterial Membrane ◽

Lipid Ii ◽

Lacticin 3147 ◽

Lacticin 481

ABSTRACT Mersacidin binds to lipid II and thus blocks the transglycosylation step of the cell wall biosynthesis. Binding of lipid II involves a special motif, the so-called mersacidin-lipid II binding motif, which is conserved in a major subgroup of lantibiotics. We analyzed the role of Ca2+ ions in the mode of action of mersacidin and some related peptides containing a mersacidin-like lipid II binding motif. We found that the stimulating effect of Ca2+ ions on the antimicrobial activity known for mersacidin also applies to plantaricin C and lacticin 3147. Ca2+ ions appear to facilitate the interaction of the lantibiotics with the bacterial membrane and with lipid II rather than being an essential part of a peptide-lipid II complex. In the case of lacticin 481, both the interaction with lipid II and the antimicrobial activity were Ca2+ independent.

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Interactions of the antimicrobial peptide nisin Z with conventional antibiotics and the use of nanostructured lipid carriers to enhance antimicrobial activity

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2017.04.071 ◽

2017 ◽

Vol 526 (1-2) ◽

pp. 244-253 ◽

Cited By ~ 28

Author(s):

Angélique Lewies ◽

Johannes Frederik Wentzel ◽

Anine Jordaan ◽

Carlos Bezuidenhout ◽

Lissinda Hester Du Plessis

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptide ◽

Nanostructured Lipid Carriers ◽

Nisin Z ◽

Conventional Antibiotics

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Lactococcus lactis RBT18: From the Rainbow Trout Farm to the Lab, the Tale of a Nisin Z Producer

Proceedings ◽

10.3390/proceedings2020066008 ◽

2020 ◽

Vol 66 (1) ◽

pp. 8

Author(s):

Diogo Contente ◽

Javier Feito ◽

Juan Borrero ◽

Nuria Peña ◽

Estefanía Muñoz-Atienza ◽

...

Keyword(s):

Antimicrobial Activity ◽

Rainbow Trout ◽

Antimicrobial Properties ◽

Bacterial Pathogen ◽

Pathogen Resistance ◽

Limiting Factors ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Nisin Z

Infectious diseases, such as lactococcosis caused by Lactococcus garvieae, are portrayed as critical limiting factors in aquaculture. The antimicrobial properties of lactic acid bacteria (LAB), mainly the production of organic acids and bacteriocins (e.g., the lanthionine containing nisins A and Z; NisA and NisZ, respectively), led to propose LAB as probiotics to be used as an alternative and/or complementary strategy to vaccination and chemotherapy in aquaculture. L. lactis RBT18, isolated from cultured rainbow trout (Oncorhynchus mykiss, Walbaum), exerts strong, direct, and extracellular antimicrobial activity against L. garvieae and other ichthyopathogens, with the latter being heat-resistant (100 °C, 10 min), and thus suggesting the involvement of a thermostable antimicrobial compound (i.e., bacteriocin). Cross-immunity tests using the agar well diffusion test (ADT) and PCR assays suggested that NisA/Z is the bacteriocin responsible for the extracellular antimicrobial activity exerted by L. lactis RBT18. To demonstrate this hypothesis, the bacteriocin was purified to homogeneity by two multi-chromatographic procedures. MALDI TOF-MS analyses of purified samples after the last reverse-phase chromatography step identified the presence of NisZ (3330 Da), and its oxidized form (3346 Da), derived from the oxidation of a lanthionine ring. The oxidized NisZ showed a diminished antimicrobial activity that would increase the chances of bacterial pathogens to evade its antimicrobial activity. Further experiments are necessary to assess the in vitro and in vivo safety and efficiency of L. lactis RBT18 as a probiotic in aquaculture, but also to optimize the environmental conditions to reduce bacteriocin oxidation and thus bacterial pathogen resistance.

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A Foodgrade Preparation of Nisin from Diluted Milk Fermented with Lactococcus lactis W8

Journal of Food Protection ◽

10.4315/0362-028x-72.12.2615 ◽

2009 ◽

Vol 72 (12) ◽

pp. 2615-2617 ◽

Cited By ~ 4

Author(s):

SURANJITA MITRA ◽

BIDHAN CHANDRA MUKHOPADHYAY ◽

SWADESH RANJAN BISWAS

Keyword(s):

Antimicrobial Activity ◽

Lactococcus Lactis ◽

Food Industry ◽

Skim Milk ◽

Cost Effective ◽

Fermented Milk ◽

Maximum Production ◽

Nisin Z ◽

Liquid Part ◽

Lactis Strain

Lactococcus lactis strain W8, which contains the nisin Z gene in its genome, grew well and produced nisin in cow's milk at temperatures of 30 to 37°C. Maximum production of nisin was achieved at 6 h and was 4,000 activity units (AU) per ml in skim milk and 2,400 AU/ml in 3% fat milk. The organism produced nisin even in 20 times diluted skim milk and 3% fat milk at 1,000 and 600 AU/ml, respectively. Boiling of the fermented milk (pH 4.2) made with this culture allowed the separation of the liquid part (whey) from the curd. When 20 times diluted skim milk was fermented and the whey derived from it was lyophilized, the yield of nisin was 60,000 AU/g. The antimicrobial activity of the nisin preparation was stable for at least 1 year at refrigeration temperature. L. lactis W8 may have significant applications in the food industry for a cost-effective natural nisin preparation.

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Antimicrobial activity of the Nisin Z producer Lactococcus lactis subsp. lactis Lc08 against Listeria monocytogenes in skim milk

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/s0102-09352013000500037 ◽

2013 ◽

Vol 65 (5) ◽

pp. 1554-1560 ◽

Cited By ~ 8

Author(s):

L.M. Perin ◽

R.O. Miranda ◽

A.C. Camargo ◽

M. Colombo ◽

A.F. Carvalho ◽

...

Keyword(s):

Antimicrobial Activity ◽

Listeria Monocytogenes ◽

Lactococcus Lactis ◽

Food Systems ◽

Skim Milk ◽

In Vitro Tests ◽

Lactococcus Lactis Subsp ◽

Ph Values ◽

Nisin Z

The presented study aimed to verify the effect of different pH values, enzyme solutions and heat treatments on the antimicrobial activity of the bacteriocinogenic strain Lactococcus lactis subsp. lactis Lc08 and to test their antimicrobial activity against Listeria monocytogenes in reconstituted skim milk at refrigeration temperatures. This strain was previously described as a nisin Z producer and capable of inhibiting L. monocytogenes growth in in vitro tests. The antimicrobial activity of the bacteriocin cell-free supernatant of Lc08 was sensitive to enzyme treatments (except papain). The pH values and heating (65ºC for 30min, 75ºC for 15s) had no apparent effect on the antimicrobial activity of the bacteriocin produced by Lc08. Only treatment at autoclave conditions result in loss of their antimicrobial activity. Lc08 presented antimicrobial activity against L. monocytogenes in the milk system after 12h at 25ºC. No effect was found at 7ºC. The results show the application viability of the Lc08 in food systems as a biopreservative against L. monocytogenes.

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