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Development of Active Compounds to Combat Antibiotic Resistant Microorganisms
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Development of Active Compounds to Combat Antibiotic Resistant Microorganisms

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 14821

Special Issue Editors

Dr. Aleksandra Królicka

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Guest Editor
Intercollegiate Faculty of Biotechnology UG-MUG, Laboratory of Biologically Active Compounds, University of Gdansk, 80-307 Gdansk, Poland
Interests: plant cell tissue; synergistic combination of drugs; biologically active compounds; transformation; phytopharmaceuticals; green synthesis of nanoparticles; drug resistance of bacteria
Special Issues, Collections and Topics in MDPI journals
Dr. Marta Krychowiak-Maśnicka

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Co-Guest Editor
Intercollegiate Faculty of Biotechnology UG-MUG, Laboratory of Biologically Active Compounds, University of Gdansk, 80-307 Gdansk, Poland
Interests: plant secondary metabolites; bacterial pathogens; antimicrobials; antibiotic resistance; nanotechnology; drug synergy; drug antagonism; Caenorhabditis elegans

Special Issue Information

Dear Colleagues,

While the discovery of antibiotics in the mid-20th century transformed human health, several antibiotic-resistant bacterial strains were identified in the decades that followed. Currently, despite the broad spectrum of antimicrobial compounds, bacterial infections are among the leading causes of death. Moreover, infections resulting from multidrug-resistant bacteria (MDR) strains are an increasing problem in modern medicine, with the ESCAPE group comprising the most threatening bacteria species. Due to bacterial resistance and a limited possibility of a new antibiotic breakthrough, we are inevitably faced with further development of new therapeutic methods to combat human bacterial pathogens.

The mechanisms of bacterial resistance are diverse and include such defense mechanisms as drug enzymatic degradation, removal of compound with the use of pumps (active transport), modifications of drug-target sites of action, or creation of an alternative metabolic pathway. The extensive defense mechanisms presented by bacteria demand a combined effort, encompassing various fields of research, from plant sciences, nanotechnology, chemistry, to computer modeling.

To address the Special Issue of treating bacterial infections caused by MDR bacteria, we are searching for new antibiotics, natural-occurring antibacterial compounds, e.g., plant secondary metabolites or peptides, synthetic substances, e.g., metal nanoparticles, and combining antibacterial substances and/or therapies aimed at obtaining a synergistic effect to prevent bacterial resistance. Reduction in effective doses and diminished toxicity towards human cells, as well as the final multi-target antimicrobial effect, are significant advantages of synergy.

Dr. Aleksandra Królicka

Dr. Marta Krychowiak-Maśnicka

Guest Editor

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Keywords

  • metal nanoparticles
  • in vitro and in vivo studies
  • plant secondary metabolites
  • synthetic peptides
  • new antimicrobials
  • antimicrobial activity
  • non-toxic towards eukaryotic cells
  • computer modeling
  • artificial intelligence algorithms

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Published Papers (4 papers)

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Research

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18 pages, 2709 KiB  
Article
Dietary Isothiocyanates, Sulforaphane and 2-Phenethyl Isothiocyanate, Effectively Impair Vibrio cholerae Virulence
by Klaudyna Krause, Agnieszka Pyrczak-Felczykowska, Monika Karczewska, Magdalena Narajczyk, Anna Herman-Antosiewicz, Agnieszka Szalewska-Pałasz and Dariusz Nowicki
Int. J. Mol. Sci. 2021, 22(19), 10187; https://doi.org/10.3390/ijms221910187 - 22 Sep 2021
Cited by 8 | Viewed by 2390
Abstract
Vibrio cholerae represents a constant threat to public health, causing widespread infections, especially in developing countries with a significant number of fatalities and serious complications every year. The standard treatment by oral rehydration does not eliminate the source of infection, while increasing antibiotic [...] Read more.
Vibrio cholerae represents a constant threat to public health, causing widespread infections, especially in developing countries with a significant number of fatalities and serious complications every year. The standard treatment by oral rehydration does not eliminate the source of infection, while increasing antibiotic resistance among pathogenic V. cholerae strains makes the therapy difficult. Thus, we assessed the antibacterial potential of plant-derived phytoncides, isothiocyanates (ITC), against V. cholerae O365 strain. Sulforaphane (SFN) and 2-phenethyl isothiocyanate (PEITC) ability to inhibit bacterial growth was assessed. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values indicate that these compounds possess antibacterial activity and are also effective against cells growing in a biofilm. Tested ITC caused accumulation of stringent response alarmone, ppGpp, which indicates induction of the global stress response. It was accompanied by bacterial cytoplasm shrinkage, the inhibition of the DNA, and RNA synthesis as well as downregulation of the expression of virulence factors. Most importantly, ITC reduced the toxicity of V. cholerae in the in vitro assays (against Vero and HeLa cells) and in vivo, using Galleria mellonella larvae as an infection model. In conclusion, our data indicate that ITCs might be considered promising antibacterial agents in V. cholerae infections. Full article
(This article belongs to the Special Issue Development of Active Compounds to Combat Antibiotic Resistant Microorganisms)
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27 pages, 4876 KiB  
Article
Fatty Acids-Enriched Fractions of Hermetia illucens (Black Soldier Fly) Larvae Fat Can Combat MDR Pathogenic Fish Bacteria Aeromonas spp.
by Heakal Mohamed, Elena Marusich, Yuriy Afanasev and Sergey Leonov
Int. J. Mol. Sci. 2021, 22(16), 8829; https://doi.org/10.3390/ijms22168829 - 17 Aug 2021
Cited by 11 | Viewed by 4032
Abstract
Aeromonas spp. cause many diseases in aquaculture habitats. Hermetia illucens (Hi) larvae were used as feed-in aquacultures and in eradicating pathogenic fish bacteria. In the present study, we applied consecutive extractions of the same biomass of BSFL fat using the acidic water–methanol solution. [...] Read more.
Aeromonas spp. cause many diseases in aquaculture habitats. Hermetia illucens (Hi) larvae were used as feed-in aquacultures and in eradicating pathogenic fish bacteria. In the present study, we applied consecutive extractions of the same biomass of BSFL fat using the acidic water–methanol solution. The major constituents of the sequential extracts (SEs) were free fatty acids (FFAs), and fatty acids derivatives as identified by gas chromatography spectrometry (GC-MS). Our improved procedure enabled gradual enrichment in the unsaturated fatty acids (USFAs) content in our SEs. The present study aimed to compare the composition and antimicrobial properties of SEs. Among actual fish pathogens, A. hydrophila and A. salmonicida demonstrated multiple drug resistance (MDR) against different recommended standard antibiotics: A. salmonicida was resistant to six, while A. hydrophila was resistant to four antibiotics from ten used in the present study. For the first time, we demonstrated the high dose-dependent antibacterial activity of each SE against Aeromonas spp., especially MDR A. salmonicida. The bacteriostatic and bactericidal (MIC/MBC) activity of SEs was significantly enhanced through the sequential extractions. The third sequential extract (AWME3) possessed the highest activity against Aeromonas spp.: inhibition zone diameters were in the range (21.47 ± 0.14–20.83 ± 0.22 mm) at a concentration of 40 mg/mL, MIC values ranged between 0.09 and 0.38 mg/mL for A. hydrophila and A. salmonicida, respectively. AWME3 MBC values recorded 0.19 and 0.38 mg/mL, while MIC50 values were 0.065 ± 0.004 and 0.22 ± 0.005 mg/mL against A. hydrophila and A. salmonicida, respectively. Thus, the larvae fat from Hermitia illucens may serve as an excellent reservoir of bioactive molecules with good capacity to eradicate the multidrug-resistant bacteria, having promising potential for practical application in the aquaculture field. Full article
(This article belongs to the Special Issue Development of Active Compounds to Combat Antibiotic Resistant Microorganisms)
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13 pages, 2329 KiB  
Article
Potential of Silver Nanoparticles in Overcoming the Intrinsic Resistance of Pseudomonas aeruginosa to Secondary Metabolites from Carnivorous Plants
by Marta Krychowiak-Maśnicka, Mirosława Krauze-Baranowska, Sylwia Godlewska, Zbigniew Kaczyński, Aleksandra Bielicka-Giełdoń, Natalia Grzegorczyk, Magdalena Narajczyk, Joanna E. Frackowiak and Aleksandra Krolicka
Int. J. Mol. Sci. 2021, 22(9), 4849; https://doi.org/10.3390/ijms22094849 - 3 May 2021
Cited by 6 | Viewed by 2961
Abstract
Carnivorous plants are exemplary natural sources of secondary metabolites with biological activity. However, the therapeutic antimicrobial potential of these compounds is limited due to intrinsic resistance of selected bacterial pathogens, among which Pseudomonas aeruginosa represents an extreme example. The objective of the study [...] Read more.
Carnivorous plants are exemplary natural sources of secondary metabolites with biological activity. However, the therapeutic antimicrobial potential of these compounds is limited due to intrinsic resistance of selected bacterial pathogens, among which Pseudomonas aeruginosa represents an extreme example. The objective of the study was to overcome the intrinsic resistance of P. aeruginosa by combining silver nanoparticles (AgNPs) with secondary metabolites from selected carnivorous plant species. We employed the broth microdilution method, the checkerboard titration technique and comprehensive phytochemical analyses to define interactions between nanoparticles and active compounds from carnivorous plants. It has been confirmed that P. aeruginosa is resistant to a broad range of secondary metabolites from carnivorous plants, i.e., naphthoquinones, flavonoids, phenolic acids (MBC = 512 µg mL−1) and only weakly sensitive to their mixtures, i.e., extracts and extracts’ fractions. However, it was shown that the antimicrobial activity of extracts and fractions with a significant level of naphthoquinone (plumbagin) was significantly enhanced by AgNPs. Our studies clearly demonstrated a crucial role of naphthoquinones in AgNPs and extract interaction, as well as depicted the potential of AgNPs to restore the bactericidal activity of naphthoquinones towards P. aeruginosa. Our findings indicate the significant potential of nanoparticles to modulate the activity of selected secondary metabolites and revisit their antimicrobial potential towards human pathogenic bacteria. Full article
(This article belongs to the Special Issue Development of Active Compounds to Combat Antibiotic Resistant Microorganisms)
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Review

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20 pages, 11197 KiB  
Review
Updated Information on Antimicrobial Activity of Hydrazide–Hydrazones
by Łukasz Popiołek
Int. J. Mol. Sci. 2021, 22(17), 9389; https://doi.org/10.3390/ijms22179389 - 30 Aug 2021
Cited by 64 | Viewed by 4472
Abstract
Hydrazide–hydrazones possess a wide spectrum of bioactivity, including antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antidepressant, antiviral, and antiprotozoal properties. This review is focused on the latest scientific reports regarding antibacterial, antimycobacterial, and antifungal activities of hydrazide–hydrazones published between 2017 and 2021. The molecules [...] Read more.
Hydrazide–hydrazones possess a wide spectrum of bioactivity, including antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antidepressant, antiviral, and antiprotozoal properties. This review is focused on the latest scientific reports regarding antibacterial, antimycobacterial, and antifungal activities of hydrazide–hydrazones published between 2017 and 2021. The molecules and their chemical structures presented in this article are the most active derivatives, with discussed activities having a hydrazide–hydrazone moiety as the main scaffold or as a side chain. Presented information constitute a concise summary, which may be used as a practical guide for further design of new molecules with antimicrobial activity. Full article
(This article belongs to the Special Issue Development of Active Compounds to Combat Antibiotic Resistant Microorganisms)
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