Lantibiotics: A Candidate for Future Generation of Antibiotics

Emergence of multi-resistant pathogens has urged the exploration of antibiotic repertoires. The long reliability on the glycopeptide antibiotic vancomycin against fatal diseases caused by Gram-positive bacteria is also in wrecked to insist on finding more promising alternative antibiotics. The peptide antibiotic nisin is effective against vancomycin resistant bacteria. Nisin is the first lantibiotic that was discovered before penicillin and has been widely used as a safe alternative for chemical reagents in food preservation in around 50 countries for over 40 years without natural resistance development. Therefore, lantibiotics are one of the most promising alternative candidate for future antibiotics that maintain their antibacterial efficacy by many modes of action. Till now, more than 60 lantibiotics have been isolated, identified and characterized. We explained various aspects of biosynthesis, grouping, mutagenesis, activities and modes of action of lantibiotics in this review. DOI: http://dx.doi.org/10.3329/sjm.v1i1.9096 Stamford Journal of Microbiology, Vol.1(1), July 2011, p.1-12

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Bacteriocins of Gram-positive bacteria having activity spectra extending beyond closely-related species

Beneficial Microbes ◽

10.3920/bm2018.0126 ◽

2019 ◽

Vol 10 (3) ◽

pp. 315-328 ◽

Cited By ~ 17

Author(s):

S.D. Todorov ◽

B.D.G. de Melo Franco ◽

J.R. Tagg

Keyword(s):

Critical Points ◽

Anticancer Agents ◽

Multidrug Resistant ◽

Food Preservation ◽

Resistant Bacteria ◽

Closely Related Species ◽

Gram Positive Bacteria ◽

Activity Spectrum ◽

Novel Applications ◽

Selection Of

Bacteriocins are bacterially-produced antimicrobial peptides that have killing activity principally against other relatively closely-related bacteria. Some bacteriocins of the lactic acid bacteria (LAB) have for many years been extensively applied in food biopreservation. However, especially during the last decade, a number of reports have appeared about unanticipated extensions to the generally rather narrow anti-bacterial activity spectrum of some of the LAB bacteriocins and novel applications have been proposed for bacteriocins ranging from controlling the growth of an increasingly-heterogeneous variety of pathogens, including Gram-negative multidrug resistant bacteria, viruses, yeasts, and in particular, difficult to control Mycobacterium spp., to their potential application as anticancer agents. How best can we assess this now rapidly-accumulating stream of reports on potential future applications of bacteriocins? Where is the line between realistic, science-based proposals and highly-speculative fiction and what are the ‘critical points’ that might help us to draw this line? In this review, we have attempted to analyse a selection of the presently-available data concerning relatively ‘unorthodox’ (i.e. beyond food preservation) applications of bacteriocins, and, by utilising our set of ‘critical points’, we endeavour to identify essential or/and missing information that appear crucial for success of the proposed applications.

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The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent

Antibiotics ◽

10.3390/antibiotics10060650 ◽

2021 ◽

Vol 10 (6) ◽

pp. 650

Author(s):

Kylen E. Ridyard ◽

Joerg Overhage

Keyword(s):

Bacterial Infections ◽

Antimicrobial Properties ◽

Cross Resistance ◽

Resistant Bacteria ◽

Peptide Antibiotic ◽

Adaptive Responses ◽

Antibiotic Resistant ◽

Structural Modifications ◽

Immobilization Techniques ◽

Conventional Antibiotics

The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.

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Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

Molecules ◽

10.3390/molecules26010170 ◽

2020 ◽

Vol 26 (1) ◽

pp. 170

Author(s):

Urszula Kosikowska ◽

Monika Wujec ◽

Nazar Trotsko ◽

Wojciech Płonka ◽

Piotr Paneth ◽

...

Keyword(s):

Antibacterial Activity ◽

Methicillin Resistant Staphylococcus Aureus ◽

Resistant Bacteria ◽

Binding Affinities ◽

Substitution Pattern ◽

Minimal Inhibitory Concentrations ◽

Gram Positive Bacteria ◽

Structure Activity ◽

Drug Resistant Bacteria ◽

Reference Strains

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

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Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum

Molecular and Cellular Biochemistry ◽

10.1007/s11010-021-04181-7 ◽

2021 ◽

Author(s):

Erum Malik ◽

David A. Phoenix ◽

Timothy J. Snape ◽

Frederick Harris ◽

Jaipaul Singh ◽

...

Keyword(s):

Helical Structure ◽

Food Preservation ◽

Forming Process ◽

Gram Positive ◽

Gram Negative ◽

Bacterial Membranes ◽

Gram Positive Bacteria ◽

Alkaline Conditions ◽

Ph Dependent ◽

Gram Negative Organisms

AbstractHere the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.25 μM). E2EM-lin adopted an α-helical structure in the presence of bacterial membranes that increased as pH was increased from 6 to 8 (↑ 15.5–26.9%), whilst similar increases in pH enhanced the ability of the peptide to penetrate (↑ 2.3–5.1 mN m−1) and lyse (↑ 15.1–32.5%) these membranes. Theoretical analysis predicted that this membranolytic mechanism involved a tilted segment, that increased along the α-helical long axis of E2EM-lin (1–23) in the N → C direction, with − < µH > increasing overall from circa − 0.8 to − 0.3. In combination, these data showed that E2EM-lin killed bacteria via novel mechanisms that were enhanced by alkaline conditions and involved the formation of tilted and membranolytic, α-helical structure. The preference of E2EM-lin for Gram-positive bacteria over Gram-negative organisms was primarily driven by the superior ability of phosphatidylglycerol to induce α-helical structure in the peptide as compared to phosphatidylethanolamine. These data were used to generate a novel pore-forming model for the membranolytic activity of E2EM-lin, which would appear to be the first, major reported instance of pH dependent AMPs with alkaline optima using tilted structure to drive a pore-forming process. It is proposed that E2EM-lin has the potential for development to serve purposes ranging from therapeutic usage, such as chronic wound disinfection, to food preservation by killing food spoilage organisms.

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Distinct Chemistries Define the Diverse Biological Effects of Plasma Activated Water Generated with Spark and Glow Plasma Discharges

Applied Sciences ◽

10.3390/app11031178 ◽

2021 ◽

Vol 11 (3) ◽

pp. 1178

Author(s):

Evanthia Tsoukou ◽

Maxime Delit ◽

Louise Treint ◽

Paula Bourke ◽

Daniela Boehm

Keyword(s):

Mammalian Cells ◽

Biomedical Application ◽

Biological Effects ◽

Mode Of Delivery ◽

Chemical Species ◽

Resistant Bacteria ◽

Cytotoxic Activities ◽

Promising Alternative ◽

Plasma Activated Water

The spread of multidrug-resistant bacteria poses a significant threat to human health. Plasma activated liquids (PAL) could be a promising alternative for microbial decontamination, where different PAL can possess diverse antimicrobial efficacies and cytotoxic profiles, depending on the range and concentration of their reactive chemical species. In this research, the biological activity of plasma activated water (PAW) on different biological targets including both microbiological and mammalian cells was investigated in vitro. The aim was to further an understanding of the specific role of distinct plasma reactive species, which is required to tailor plasma activated liquids for use in applications where high antimicrobial activity is required without adversely affecting the biology of eukaryotic cells. PAW was generated by glow and spark discharges, which provide selective generation of hydrogen peroxide, nitrite and nitrate in the liquid. The PAW made by either spark or glow discharges showed similar antimicrobial efficacy and stability of activity, despite the very different reactive oxygen species (ROS) and reactive nitrogen species profiles (RNS). However, different trends were observed for cytotoxic activities and effects on enzyme function, which were translated through the selective chemical species generation. These findings indicate very distinct mechanisms of action which may be exploited when tailoring plasma activated liquids to various applications. A remarkable stability to heat and pressure was noted for PAW generated with this set up, which broadens the application potential. These features also suggest that post plasma modifications and post generation stability can be harnessed as a further means of modulating the chemistry, activity and mode of delivery of plasma functionalised liquids. Overall, these results further understanding on how PAL generation may be tuned to provide candidate disinfectant agents for biomedical application or for bio-decontamination in diverse areas.

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UJI RESISTENSI BAKTERI BACILLUS SP YANG DIISOLASI DARI PLAK GIGI TERHADAP MERKURI DAN ERITROMISIN

Jurnal e-Biomedik ◽

10.35790/ebm.3.1.2015.6610 ◽

2015 ◽

Vol 3 (1) ◽

Author(s):

Terence Kanzil ◽

Fatimawali . ◽

Aaltje Manampiring

Keyword(s):

Heavy Metal ◽

Toxic Effects ◽

Resistant Bacteria ◽

Bacillus Sp ◽

Gram Positive ◽

Toxic Heavy Metal ◽

Mer Operon ◽

Dental Fillings ◽

Gram Positive Bacteria ◽

Mercury Resistant Bacteria

Abstract: Mercury is a toxic heavy metal that is used for dental fillings in the form of amalgam. To reduce the toxic effects produced by mercury, mercury resistant bacteria can be used. Bacillus sp is a gram-positive bacteria that is resistant to mercury. Besides having the mer operon genes that can transform Hg2+ to Hg0 that is less toxic, Bacillus sp bacteria also produce esterase that cause these bacteria resistant to erythromycin antibiotic. Erythromycin is a macrolide class of antibiotic used for the treatment of diseases caused by Gram-positive bacteria, especially Staphylococcus and Diphtheroids. To determine the resistance of Bacillus sp bacteria against mercury and erythromycin antibiotic. This study used a descriptive exploratory method with samples of bacteria and mercury are already available in the Laboratory of Pharmaceutical Microbiology. Based on the research that has been conducted, showed that the Bacillus sp bacteria is resistant to mercury and erythromycin.Keywords: bacteria, bacillus sp, resistant, mercury, erythromycinAbstrak: Merkuri merupakan logam berat bersifat toksik yang digunakan untuk penambalan gigi dalam bentuk amalgam. Untuk mengurangi efek toksik yang dihasilkan oleh merkuri, dapat digunakan bakteri resisten merkuri. Bakteri Bacillus sp merupakan bakteri gram positif yang resisten terhadap merkuri. Selain memiliki gen mer operon yang dapat mengubah Hg2+ menjadi Hg0 yang kurang toksik, bakteri Bacillus sp juga membentuk esterase yang menyebabkan terjadinya resisten bakteri ini terhadap antibiotik eritromisin. Eritromisin adalah antibiotik golongan makrolid yang digunakan untuk pengobatan penyakit akibat bakteri Gram positif khususnya Staphylococcus dan Diphtheroids. Untuk mengetahui resistensi bakteri Bacillus sp terhadap merkuri dan antibiotik eritromisin. Penelitian ini menggunakan metode deskriptif eksploratif dengan sampel bakteri dan merkuri yang sudah tersedia di Laboratorium Mikrobiologi Farmasi. Berdasarkan hasil penelitian yang telah dilakukan, diperoleh bahwa bakteri Bacillus sp resisten terhadap merkuri dan eritromisin.Kata Kunci: bakteri, bacillus sp, resisten, merkuri, eritromisin

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Antibacterial Activity of Prismatomeris tetrandra K. Schum Root Extract against Antibiotic Resistance Bacteria

Walailak Journal of Science and Technology (WJST) ◽

10.48048/wjst.2019.6291 ◽

2018 ◽

Vol 16 (5) ◽

pp. 341-348

Author(s):

On-Anong SOMSAP

Keyword(s):

Antibacterial Activity ◽

Antibiotic Resistance ◽

Culture Broth ◽

Diffusion Method ◽

Resistant Bacteria ◽

Root Extract ◽

Gram Negative Bacteria ◽

Antibiotic Resistant ◽

Gram Positive Bacteria ◽

Colony Forming Units

Antibiotic resistance bacteria has become an increasing problem now today due to many factors. This study investigates the efficacy of Prismatomeris tetrandra K. Schum root extract as a new source of antibacterial activity for antibiotic resistant bacteria using agar well diffusion method. The results showed that S. aureus TISTR517 exhibited more sensitivity to P. tetrandra K. Schum root extract than other Gram-positive bacteria indicator strains. On the other hand, Gram-negative bacteria exhibited resistance to P. tetrandra K. Schum root extract. The study further showed the activity between P. tetrandra K. Schum root extract and gentamycin (10 µg), it revealed that MRSA142 was resistant to gentamycin (10µg) but sensitive to P. tetrandra K. Schum root extract. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was evaluated by using S. aureus TISTR517 and MRSA142 as indicator strains. The MIC value was 0.59 mg/mL and 1.17 mg/mL for S. aureus TISTR517 and MRSA142, respectively. MBC assay demonstrated that the MBC value was 9.75 mg/mL and 150 mg/mL for S. aureus TISTR517 and MRSA142 respectively. The mode of action was investigated with the presence of P. tetrandra K. Schum root extract in the culture broth. The action of P. tetrandra K. Schum root extract was revealed of bacteriostatic activity due to the Optical density (OD) at 600 nm and Colony-Forming Units (CFU) of indicator strains were continuously decreased.

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Molecular Characterization of Isolated Multidrug-Resistant Bacteria from Tertiary Care Hospitals of Ahmedabad: A Comparison Study Between Previous to COVID-19 and Current Scenario

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.15.2.33 ◽

2021 ◽

Author(s):

Anurag D. Zaveri ◽

Dilip N. Zaveri ◽

Lakshmi Bhaskaran

Keyword(s):

Molecular Characterization ◽

Tertiary Care ◽

Future Generation ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

E Coli ◽

Pseudomonas Spp ◽

Bacillus Spp ◽

Current Scenario ◽

Klebsiella Spp

Hospital Acquired Infections (HAIs) are a significant concern for healthcare setups, as it increases the overall cost of treatment, patients stay in hospitals, making them susceptible to secondary and tertiary infections and, sometimes, mortality1. To prevent or control HAIs, evaluating the organisms isolated from the critically maintained areas is considered of epitome importance and everlasting practice in the healthcare industry. Identifying such organisms and screening them for antibiotic resistance is mandatory, but it also helps professionals understand colonization trends. Sensitive areas of healthcare setups were screened monthly from years 2017 to 2020. A total of 4400 samples of hospital hygiene, e.g., intravenous drip stands, ventilator surface, anesthetist’s trolley, patient’s bed, instrument trolley, etcetera, were collected. Isolated organisms were cultured and screened using the CLSI technique. E. coli, Pseudomonas spp., and Klebsiella spp. were found in both previous to COVID current samples. Multidrug-resistant organisms were subjected to molecular characterization to detect the presence of carbapenem genes. Evaluation data of both pre-and during Coronavirus Disease or COVID-19 were compared. The prevalence of pathogenic (Klebsiella spp., E. coli, and Pseudomonas spp.) and non-pathogenic (Staphylococcus aureus and Bacillus spp.) strains in healthcare setups decreased drastically (Klebsiella spp. from 80% to 20%, E.coli from 90% to 10% and Pseudomonas spp. from 80% to 20%). It is possible only because of the awareness in non-specialists and healthcare workers due to the unforeseen critical situation proving to be a blessing for the future generation.

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Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

Molecules ◽

10.3390/molecules24112077 ◽

2019 ◽

Vol 24 (11) ◽

pp. 2077 ◽

Cited By ~ 1

Author(s):

Andrea Díaz-Roa ◽

Abraham Espinoza-Culupú ◽

Orlando Torres-García ◽

Monamaris M. Borges ◽

Ivan N. Avino ◽

...

Keyword(s):

Micrococcus Luteus ◽

Multidrug Resistant ◽

Peptide Sequence ◽

Resistant Bacteria ◽

Gram Positive ◽

Antimicrobial Drugs ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Conserved Domain ◽

Health Institutions

Antibiotic resistance is at dangerous levels and increasing worldwide. The search for new antimicrobial drugs to counteract this problem is a priority for health institutions and organizations, both globally and in individual countries. Sarconesiopsis magellanica blowfly larval excretions and secretions (ES) are an important source for isolating antimicrobial peptides (AMPs). This study aims to identify and characterize a new S. magellanica AMP. RP-HPLC was used to fractionate ES, using C18 columns, and their antimicrobial activity was evaluated. The peptide sequence of the fraction collected at 43.7 min was determined by mass spectrometry (MS). Fluorescence and electronic microscopy were used to evaluate the mechanism of action. Toxicity was tested on HeLa cells and human erythrocytes; physicochemical properties were evaluated. The molecule in the ES was characterized as sarconesin II and it showed activity against Gram-negative (Escherichia coli MG1655, Pseudomonas aeruginosa ATCC 27853, P. aeruginosa PA14) and Gram-positive (Staphylococcus aureus ATCC 29213, Micrococcus luteus A270) bacteria. The lowest minimum inhibitory concentration obtained was 1.9 μM for M. luteus A270; the AMP had no toxicity in any cells tested here and its action in bacterial membrane and DNA was confirmed. Sarconesin II was documented as a conserved domain of the ATP synthase protein belonging to the Fli-1 superfamily. The data reported here indicated that peptides could be alternative therapeutic candidates for use in infections against Gram-negative and Gram-positive bacteria and eventually as a new resource of compounds for combating multidrug-resistant bacteria.

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Grapevine Resistance to the Nematode Xiphinema index Is Durable in Muscadine-Derived Plants Obtained from Hardwood Cuttings but Not from In Vitro

Phytopathology ◽

10.1094/phyto-01-20-0008-r ◽

2020 ◽

Vol 110 (9) ◽

pp. 1565-1571

Author(s):

Van Chung Nguyen ◽

Jean-Pascal Tandonnet ◽

Samira Khallouk ◽

Cyril Van Ghelder ◽

Ulysse Portier ◽

...

Keyword(s):

Natural Resistance ◽

Parasitic Nematodes ◽

Promising Alternative ◽

Nematode Reproduction ◽

Xiphinema Index ◽

Plant Nematode ◽

Hardwood Cutting ◽

Muscadinia Rotundifolia ◽

Reproduction Factor

Breeding for varieties carrying natural resistance (R) against plant-parasitic nematodes is a promising alternative to nematicide ban. In perennial crops, the long plant−nematode interaction increases the risk for R breaking and R durability is a real challenge. In grapevine, the nematode Xiphinema index has a high economic impact by transmitting Grapevine fanleaf virus (GFLV) and, to delay GFLV transmission, rootstocks resistant to this vector are being selected, using Muscadinia rotundifolia in particular as an R source. To optimize in fine this strategy, the durability has been studied under controlled conditions in F1 and BC1 muscadine-derived resistant accessions previously obtained from either hardwood-cutting or in vitro propagation. After inoculation with a mix, in equal proportions, of four lines representative of the X. index diversity, multiplication on plants has been monitored 3 to 6 years. The nematode reproduction factor remained lower than 1 in resistant plants obtained from hardwood cuttings while it increased at values far beyond 1 in resistant plants of in vitro origin. Data for nematode numbers per gram of roots mostly paralleled those obtained for the reproduction factor. The effect of the propagation type on resistance over years was also evaluated for the ratio female/juvenile and the frequency of males. Altogether our results illustrate that the muscadine-derived resistance based on hardwood cuttings is durable. By contrast, in resistant and reference accessions obtained from in vitro, our data suggest that the increased nematode multiplication might be mainly due to the modification of root architecture consecutive to this propagation method.

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