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Natural Compounds: A New Strategy to Fight the Spread of Antimicrobial Resistance

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 9433

Special Issue Editor


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Guest Editor
Scuola di Medicina e Scienze della Salute, Nuovo Polo Department of Innovative Technology in Medicine and Dentistry Didattico, Edificio C, IV Livello, Università G. d’Annunzio, Chieti-Pescara, Via dei Vestini 31, 66013 Chieti, Italy
Interests: fundamental mechanisms underlying cancer; cell signalling and signal transduction; thyroid cancer; gastric cancer; erbb receptors; oxidative stress; bacterial outer membrane vesicles; cancer therapy

Special Issue Information

Dear Colleagues,

Antibiotic resistance is one of the biggest threats to global health and food security. It occurs naturally, but the overuse and misuse of antibiotics are key factors contributing to its onset. Antibiotic resistance leads to longer hospital stays, increased mortality, and higher medical costs. The microorganisms adopt many strategies to defend themselves against attack by antimicrobial drugs, including the ability to develop biofilms. Biofilms can be defined as complex structures constituted by cells within a self-produced extracellular polymeric substances matrix, a mixture of exopolysaccharides; proteins, extracellular DNA, and, in some cases, extracellular vesicles. Biofilm development induces antibiotic tolerance and protection from the host immune system, making microbial biofilms difficult to eradicate. The use of natural compounds as well as the identification of new molecules or natural compounds derivatives with antimicrobial and/or antibiofilm activities may contribute to fight the spread of antimicrobial resistance. Natural active compounds and derivatives may be used to treat microbial infections, eradication and prevention, food contamination and preservation, as well as the inhibition and/or eradication of biofilm. These agents could also be a promising starting point for an optimization process carried out by medicinal chemists to understand the structural requirements for these activities.

The proposed Special Issue will be an updated collection of articles focused on the study of single bioactive natural compounds and their semisynthetic derivatives with improved biological activity or pharmacokinetics showing potent antimicrobial and antibiofilm activities. The aim is to collect some of the most significant and recent contributions in the interdisciplinary areas of (food) microbiology, medicinal chemistry, natural products, pathology, and pharmacology for a potential application in the molecular biology field as well as in food preservation. Submissions of original research articles and review articles are strongly encouraged.

Dr. Gabriella Mincione
Guest Editor

Manuscript Submission Information

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Keywords

  • antimicrobial agents

  • antimicrobial resistance; biofilm

  • drug tolerance; nanosystems

  • anti-biofilm activity

  • natural active compounds

  • anti-quorum sensing molecules

  • new antimicrobials; bioactive agents

  • drug delivery; medicinal chemistry

  • structure–activity relationships

  • antimicrobial peptides

  • synthetic inhibitors

  • food contamination

  • medical device contamination

Published Papers (3 papers)

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Research

15 pages, 1797 KiB  
Article
Bis-Indole Alkaloids Isolated from the Sponge Spongosorites calcicola Disrupt Cell Membranes of MRSA
by Neyaz A. Khan, Navdeep Kaur, Peter Owens, Olivier P. Thomas and Aoife Boyd
Int. J. Mol. Sci. 2022, 23(4), 1991; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23041991 - 11 Feb 2022
Cited by 7 | Viewed by 2262
Abstract
Antimicrobial resistance (AMR) is a global health challenge with methicillin resistant Staphylococcus aureus (MRSA), a leading cause of nosocomial infection. In the search for novel antibiotics, marine sponges have become model organisms as they produce diverse bioactive compounds. We investigated and compared the [...] Read more.
Antimicrobial resistance (AMR) is a global health challenge with methicillin resistant Staphylococcus aureus (MRSA), a leading cause of nosocomial infection. In the search for novel antibiotics, marine sponges have become model organisms as they produce diverse bioactive compounds. We investigated and compared the antibacterial potential of 3 bis-indole alkaloids—bromodeoxytopsentin, bromotopsentin and spongotine A—isolated from the Northeastern Atlantic sponge Spongosorites calcicola. Antimicrobial activity was determined by MIC and time-kill assays. The mechanism of action of bis-indoles was assessed using bacterial cytological profiling via fluorescence microscopy. Finally, we investigated the ability of bis-indole alkaloids to decrease the cytotoxicity of pathogens upon co-incubation with HeLa cells through the measurement of mammalian cell lysis. The bis-indoles were bactericidal to clinically relevant Gram-positive pathogens including MRSA and to the Gram-negative gastroenteric pathogen Vibrio parahaemolyticus. Furthermore, the alkaloids were synergistic in combination with conventional antibiotics. Antimicrobial activity of the bis-indole alkaloids was due to rapid disruption and permeabilization of the bacterial cell membrane. Significantly, the bis-indoles reduced pathogen cytotoxicity toward mammalian cells, indicating their ability to prevent bacterial virulence. In conclusion, sponge bis-indole alkaloids are membrane-permeabilizing agents that represent good antibiotic candidates because of their potency against Gram-positive and Gram-negative bacterial pathogens. Full article
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21 pages, 15641 KiB  
Article
Evaluation of the Antimicrobial Efficacy of N-Acetyl-l-Cysteine, Rhamnolipids, and Usnic Acid—Novel Approaches to Fight Food-Borne Pathogens
by Ondrej Chlumsky, Heidi J. Smith, Albert E. Parker, Kristen Brileya, James N. Wilking, Sabina Purkrtova, Hana Michova, Pavel Ulbrich, Jitka Viktorova and Katerina Demnerova
Int. J. Mol. Sci. 2021, 22(21), 11307; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111307 - 20 Oct 2021
Cited by 4 | Viewed by 2241
Abstract
In the food industry, the increasing antimicrobial resistance of food-borne pathogens to conventional sanitizers poses the risk of food contamination and a decrease in product quality and safety. Therefore, we explored alternative antimicrobials N-Acetyl-l-cysteine (NAC), rhamnolipids (RLs), and usnic acid [...] Read more.
In the food industry, the increasing antimicrobial resistance of food-borne pathogens to conventional sanitizers poses the risk of food contamination and a decrease in product quality and safety. Therefore, we explored alternative antimicrobials N-Acetyl-l-cysteine (NAC), rhamnolipids (RLs), and usnic acid (UA) as a novel approach to prevent biofilm formation and reduce existing biofilms formed by important food-borne pathogens (three strains of Salmonella enterica and two strains of Escherichia coli, Listeria monocytogenes, Staphylococcus aureus). Their effectiveness was evaluated by determining minimum inhibitory concentrations needed for inhibition of bacterial growth, biofilm formation, metabolic activity, and biofilm reduction. Transmission electron microscopy and confocal scanning laser microscopy followed by image analysis were used to visualize and quantify the impact of tested substances on both planktonic and biofilm-associated cells. The in vitro cytotoxicity of the substances was determined as a half-maximal inhibitory concentration in five different cell lines. The results indicate relatively low cytotoxic effects of NAC in comparison to RLs and UA. In addition, NAC inhibited bacterial growth for all strains, while RLs showed overall lower inhibition and UA inhibited only the growth of Gram-positive bacteria. Even though tested substances did not remove the biofilms, NAC represents a promising tool in biofilm prevention. Full article
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14 pages, 1653 KiB  
Article
Biosensor-Assisted Adaptive Laboratory Evolution for Violacein Production
by Da-ae Gwon, Joo Yeon Seok, Gyoo Yeol Jung and Jeong Wook Lee
Int. J. Mol. Sci. 2021, 22(12), 6594; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126594 - 19 Jun 2021
Cited by 13 | Viewed by 4112
Abstract
Violacein is a naturally occurring purple pigment, widely used in cosmetics and has potent antibacterial and antiviral properties. Violacein can be produced from tryptophan, consequently sufficient tryptophan biosynthesis is the key to violacein production. However, the complicated biosynthetic pathways and regulatory mechanisms often [...] Read more.
Violacein is a naturally occurring purple pigment, widely used in cosmetics and has potent antibacterial and antiviral properties. Violacein can be produced from tryptophan, consequently sufficient tryptophan biosynthesis is the key to violacein production. However, the complicated biosynthetic pathways and regulatory mechanisms often make the tryptophan overproduction challenging in Escherichia coli. In this study, we used the adaptive laboratory evolution (ALE) strategy to improve violacein production using galactose as a carbon source. During the ALE, a tryptophan-responsive biosensor was employed to provide selection pressure to enrich tryptophan-producing cells. From the biosensor-assisted ALE, we obtained an evolved population of cells capable of effectively catabolizing galactose to tryptophan and subsequently used the population to obtain the best violacein producer. In addition, whole-genome sequencing of the evolved strain identified point mutations beneficial to the overproduction. Overall, we demonstrated that the biosensor-assisted ALE strategy could be used to rapidly and selectively evolve the producers to yield high violacein production. Full article
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