New Strategies to Counteract Antibiotic Resistance Mechanisms

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 16195

Special Issue Editors

Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi, 32-90123 Palermo, Italy
Interests: marine alkaloids; heterocycles; drug discovery; synthesis; bioactive compounds; antitumor activity; antibiofilm activity; and kinase inhibitors
Special Issues, Collections and Topics in MDPI journals
Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi, 32-90123 Palermo, Italy
Interests: antibiotic resistance; anti-biofilm agents; anti-virulence compounds; anticancer derivatives; sortase A inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotic resistance is an issue of great concern associated with a high social and economic burden.

The excessive use and misuse of antibiotics, as well as the continual evolution and adaptation of microorganisms, are the main causes of multidrug resistance. There is an urgent need for new therapeutic strategies that may restrain or inhibit the mechanisms of resistance.

Antibiotic resistance may exist at cellular and community levels (biofilm).

At the cellular level, drug resistance is essentially due to: (i) enzymatic resistance, causing inactivation of the antibiotic, (ii) chemical modification of the antibiotic target or expression of an alternative target, and (iii) changes in cell permeability (efflux pumps).

At community level, biofilm structure physically limits the penetration of antibiotics in resident bacterial cells and, moreover, the deepest layers of biofilm contain specific bacterial subpopulations, which are metabolically less active and, therefore, intrinsically resistant to conventional antibiotics.

Biofilm formation significantly contributes to microbial survival in hostile environments and it is a key virulence factor for pathogens responsible of serious chronic infections, such as pneumonia in cystic fibrosis patients, osteomyelitis, chronic wound infections and otitis. The majority of antibiotics effective on planktonic cells are inactive against biofilms.

The marine environment is an important source of compounds endowed with antimicrobial properties. Marine invertebrates, such as sponges, are a prolific source of antibacterial compounds, with many interesting modes of action. Representative examples are the bis(indole) alkaloid deoxytopsentin, isolated from the sponge Spongosorites sp, and the 1H-benzo[de][1,6]-naphthyridine alkaloid isoaaptamin, isolated from the Aaptos aaptos marine sponge, which showed potent Sortase A inhibitory activity with IC50 values of 15.67 µg/ml and IC50 of 3.7 µg/ml.

This Special Issue will focus on the development of new marine drugs effective in the treatment of antibiotic resistance mechanisms at both bacterial cell and community levels, especially on compounds able to target virulence mechanisms, such as bacterial adhesion to host tissues, without effecting microbial viability.

In particular, studies on the anti-virulence mechanisms of these compounds are especially encouraged.

Prof. Dr. Patrizia Diana
Dr. Stella Maria Cascioferro
Guest Editors

Manuscript Submission Information

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Keywords

  • Anti-virulence compounds
  • Anti-biofilm agents
  • Sortase A inhibitors
  • Anti-adhesion compounds
  • MRSA
  • Antibiotic resistance
  • Dispersal agents
  • c-di-GMP signaling
  • c-di-AMP pathway
  • efflux pump inhibitors
  • Marine drugs
  • Antibacterial compounds from marine source

Published Papers (4 papers)

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Research

11 pages, 999 KiB  
Article
A Synthetic Derivative of Antimicrobial Peptide Holothuroidin 2 from Mediterranean Sea Cucumber (Holothuria tubulosa) in the Control of Listeria monocytogenes
by Maria Grazia Cusimano, Angelo Spinello, Giampaolo Barone, Domenico Schillaci, Stella Cascioferro, Alessandra Magistrato, Barbara Parrino, Vincenzo Arizza and Maria Vitale
Mar. Drugs 2019, 17(3), 159; https://doi.org/10.3390/md17030159 - 08 Mar 2019
Cited by 27 | Viewed by 3493
Abstract
Due to the limited number of available antibiotics, antimicrobial peptides (AMPs) are considered antimicrobial candidates to fight difficult-to-treat infections such as those associated with biofilms. Marine environments are precious sources of AMPs, as shown by the recent discovery of antibiofilm properties of Holothuroidin [...] Read more.
Due to the limited number of available antibiotics, antimicrobial peptides (AMPs) are considered antimicrobial candidates to fight difficult-to-treat infections such as those associated with biofilms. Marine environments are precious sources of AMPs, as shown by the recent discovery of antibiofilm properties of Holothuroidin 2 (H2), an AMP produced by the Mediterranean sea cucumber Holothuria tubulosa. In this study, we considered the properties of a new H2 derivative, named H2d, and we tested it against seven strains of the dangerous foodborne pathogen Listeria monocytogenes. This peptide was more active than H2 in inhibiting the growth of planktonic L. monocytogenes and was able to interfere with biofilm formation at sub-minimum inhibitory concentrations (MICs). Atomic-level molecular dynamics (MD) simulations revealed insights related to the enhanced inhibitory activity of H2d, showing that the peptide is characterized by a more defined tertiary structure with respect to its ancestor. This allows the peptide to better exhibit an amphipathic character, which is an essential requirement for the interaction with cell membranes, similarly to other AMPs. Altogether, these results support the potential use of our synthetic peptide, H2d, as a template for the development of novel AMP-based drugs able to fight foodborne that are resistant to conventional antibiotics. Full article
(This article belongs to the Special Issue New Strategies to Counteract Antibiotic Resistance Mechanisms)
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8 pages, 1486 KiB  
Article
Algal Oxylipins Mediate the Resistance of Diatoms against Algicidal Bacteria
by Nils Meyer, Johanna Rettner, Markus Werner, Oliver Werz and Georg Pohnert
Mar. Drugs 2018, 16(12), 486; https://doi.org/10.3390/md16120486 - 04 Dec 2018
Cited by 39 | Viewed by 4769
Abstract
Algicidal bacteria can lyse microalgal blooms and trigger shifts within plankton communities. Resistant algal species can escape lysis, and have the opportunity to dominate the phytoplankton after a bacterial infection. Despite their important function in ecosystem regulation, little is known about mechanisms of [...] Read more.
Algicidal bacteria can lyse microalgal blooms and trigger shifts within plankton communities. Resistant algal species can escape lysis, and have the opportunity to dominate the phytoplankton after a bacterial infection. Despite their important function in ecosystem regulation, little is known about mechanisms of resistance. Here, we show that the diatom Chaetoceros didymus releases eicosanoid oxylipins into the medium, and that the lytic algicidal bacterium, Kordia algicida, induces the production of several wound-activated oxylipins in this resistant diatom. Neither releases nor an induction occurs in the susceptible diatom Skeletonema costatum that is lysed by the bacterium within a few days. Among the upregulated oxylipins, hydroxylated eicosapentaenoic acids (HEPEs) dominate. However, also, resolvins, known lipid mediators in mammals, increase upon exposure of the algae to the algicidal bacteria. The prevailing hydroxylated fatty acid, 15-HEPE, significantly inhibits growth of K. algicida at a concentration of approximately 1 µM. The oxylipin production may represent an independent line of defense of the resistant alga, acting in addition to the previously reported upregulation of proteases. Full article
(This article belongs to the Special Issue New Strategies to Counteract Antibiotic Resistance Mechanisms)
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10 pages, 4838 KiB  
Article
Antimicrobial and Antibiofilm Activity of a Recombinant Fragment of β-Thymosin of Sea Urchin Paracentrotus lividus
by Angelo Spinello, Maria Grazia Cusimano, Domenico Schillaci, Luigi Inguglia, Giampaolo Barone and Vincenzo Arizza
Mar. Drugs 2018, 16(10), 366; https://doi.org/10.3390/md16100366 - 02 Oct 2018
Cited by 17 | Viewed by 3427
Abstract
With the aim to obtain new antimicrobials against important pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, we focused on antimicrobial peptides (AMPs) from Echinoderms. An example of such peptides is Paracentrin 1 (SP1), a chemically synthesised peptide fragment of a sea [...] Read more.
With the aim to obtain new antimicrobials against important pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, we focused on antimicrobial peptides (AMPs) from Echinoderms. An example of such peptides is Paracentrin 1 (SP1), a chemically synthesised peptide fragment of a sea urchin thymosin. In the present paper, we report on the biological activity of a Paracentrin 1 derivative obtained by recombination. The recombinant paracentrin RP1, in comparison to the synthetic SP1, is 22 amino acids longer and it was considerably more active against the planktonic forms of S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 at concentrations of 50 µg/mL. Moreover, it was able to inhibit biofilm formation of staphylococcal and P. aeruginosa strains at concentrations equal to 5.0 and 10.7 µg/mL, respectively. Molecular dynamics (MD) simulations allowed to rationalise the results of the experimental investigations, providing atomistic insights on the binding of RP1 toward models of mammalian and bacterial cell membranes. Overall, the results obtained point out that RP1 shows a remarkable preference for bacterial membranes, in excellent agreement with the antibacterial activity, highlighting the promising potential of using the tested peptide as a template for the development of novel antimicrobial agents. Full article
(This article belongs to the Special Issue New Strategies to Counteract Antibiotic Resistance Mechanisms)
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15 pages, 1194 KiB  
Article
New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation
by Anna Carbone, Barbara Parrino, Maria Grazia Cusimano, Virginia Spanò, Alessandra Montalbano, Paola Barraja, Domenico Schillaci, Girolamo Cirrincione, Patrizia Diana and Stella Cascioferro
Mar. Drugs 2018, 16(8), 274; https://doi.org/10.3390/md16080274 - 04 Aug 2018
Cited by 38 | Viewed by 4091
Abstract
New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity [...] Read more.
New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC50 values against Staphylococcus aureus ATCC 25923, ranging from 0.40–2.03 µM. The new compounds showed a typical anti-virulence profile, being able to inhibit the biofilm formation without affecting the microbial growth in the planktonic form. Full article
(This article belongs to the Special Issue New Strategies to Counteract Antibiotic Resistance Mechanisms)
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