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Pharmaceutics
Special Issues
Drug Targeting towards Fighting Pathogen Bacteria
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Drug Targeting towards Fighting Pathogen Bacteria

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 12175

Special Issue Editor

Dr. Sandra N. Pinto

E-Mail Website
Guest Editor
Institute for Bioengineering and Biosciences and i4HB—Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
Interests: cell biophysics; antimicrobial agents; cancer therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

One of the major public health concerns of the 21st century is the continuous emergence of antibiotic-resistant strains, which cause a serious threat to the efficient prevention and treatment of bacterial-related infections.

Antibiotic resistance can be considered an inevitable consequence of the rambunctious and unregulated use of antibiotics, which remains a major factor facilitating the emergence of antibiotics resistance worldwide.

Several fields of medicine depend on the availability of antibiotic drugs; for instance, the immunosuppression induced by cancer therapy and long-term vascular catheter placement make cancer patients susceptible to bacterial infections often caused by resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Thus, to avoid secondary infections, cancer patients are routinely given antibiotics, which cause many side effects, including antimicrobial resistance.

Conventional antibiotics have many disadvantages, such as the development of resistance and, in some cases, a low therapeutic index. Thus, more efficient and effective compounds are urgently required.

This Special Issue aims to identify novel strategies and/or compounds that can help improve the success of bacterial treatment.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: 

  • Antimicrobial polymers;
  • Antimicrobial peptides and peptidomimetics;
  • Use of natural products;
  • Combinations of antimicrobial agents effect;
  • Inhibitors of virulence factors;
  • Use of nanoparticles;
  • Drug delivery systems;
  • Topical antimicrobial treatment;
  • Phage therapy;
  • Enzybiotics. 

This Special Issue welcomes different types of submissions, such as original research papers, short communications, reviews, case reports, and opinion papers.

I look forward to receiving your contributions.

Dr. Sandra N. Pinto
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial compounds
  • antibiotic resistance
  • antibiotics
  • bacterial infections
  • antimicrobial strategies

Published Papers (5 papers)

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Research

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20 pages, 7219 KiB  
Article
E. coli Cell Lysis Induced by Lys394 Enzyme Assisted by Magnetic Nanoparticles Exposed to Non-Heating Low-Frequency Magnetic Field
by Azizbek D. Usvaliev, Natalia G. Belogurova, Konstantin V. Pokholok, Alexander V. Finko, Andrey N. Prusov, Dmitry Yu. Golovin, Konstantin A. Miroshnikov, Yuri I. Golovin and Natalia L. Klyachko
Pharmaceutics 2023, 15(7), 1871; https://doi.org/10.3390/pharmaceutics15071871 - 03 Jul 2023
Viewed by 1262
Abstract
The spreading of microbial pathogens with more and more resistance to traditional low-molecular antibiotic agents demands new approaches to antibacterial therapy. The employment of bacteriophage enzymes capable of breaking bacterial cell walls has attracted much interest within this context. The specific features of [...] Read more.
The spreading of microbial pathogens with more and more resistance to traditional low-molecular antibiotic agents demands new approaches to antibacterial therapy. The employment of bacteriophage enzymes capable of breaking bacterial cell walls has attracted much interest within this context. The specific features of the morphology of Gram-negative bacteria prevent the effective direct usage of lytic enzymes and require assistance from additional helpers to facilitate cell lysis. The current work is devoted to the study of boosting the lysis of Escherichia coli (E. coli) JM 109 and MH 1 strains induced by Lys394 bacteriophage endolysin by means of rod-like (56 × 13 nm) magnetic nanoparticles (MNPs) activated by a non-heating low-frequency magnetic field (LF MF) with a frequency of 50 Hz and a flux density of 68.5 mT in a pulse–pause mode (1 s on and 0.3 s off). According to theoretical assumptions, the mechanism of MNP assistance is presumably based upon the disordering of the outer membrane that facilitates enzyme permeation into peptidoglycans to its substrate. It is found that the effect of the LF MF reaches an almost a twofold acceleration of the enzyme reaction, resulting in almost 80 and 70%, respectively, of lysed E. coli JM 109 and MH 1 cells in 21 min. An increase in the membrane permeability was proven by two independent experiments employing β-lactamase periplasmic enzyme leakage and Nile Red (NR) hydrophobic dye fluorescence. It is shown that the outer membrane disordering of E. coli caused by exposure to LF MF nanoparticle movement leads to almost complete (more than 80%) β-lactamase release out of the cells’ periplasm to the buffer suspension. Experiments with NR (displaying fluorescence in a non-polar medium only) reveal a drastic reduction in NR fluorescence intensity, reaching a change of an order of magnitude when exposed to LF MF. The data obtained provide evidence of changes in the bacterial cell wall structure. The result shown open up the prospects of non-heating LF MF application in enhancing enzyme activity against Gram-negative pathogens. Full article
(This article belongs to the Special Issue Drug Targeting towards Fighting Pathogen Bacteria)
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13 pages, 3056 KiB  
Article
Targeting Siderophore-Mediated Iron Uptake in M. abscessus: A New Strategy to Limit the Virulence of Non-Tuberculous Mycobacteria
by Matteo Mori, Giovanni Stelitano, Giulia Cazzaniga, Arianna Gelain, Andrea Tresoldi, Mario Cocorullo, Martina Roversi, Laurent R. Chiarelli, Martina Tomaiuolo, Pietro Delre, Giuseppe F. Mangiatordi, Anna Griego, Loris Rizzello, Alberto Cassetta, Sonia Covaceuszach, Stefania Villa and Fiorella Meneghetti
Pharmaceutics 2023, 15(2), 502; https://doi.org/10.3390/pharmaceutics15020502 - 02 Feb 2023
Cited by 6 | Viewed by 2150
Abstract
Targeting pathogenic mechanisms, rather than essential processes, represents a very attractive approach for the development of new antimycobacterial drugs. In this context, iron acquisition routes have recently emerged as potentially druggable pathways. However, the importance of siderophore biosynthesis in the virulence and pathogenicity [...] Read more.
Targeting pathogenic mechanisms, rather than essential processes, represents a very attractive approach for the development of new antimycobacterial drugs. In this context, iron acquisition routes have recently emerged as potentially druggable pathways. However, the importance of siderophore biosynthesis in the virulence and pathogenicity of M. abscessus (Mab) is still poorly understood. In this study, we investigated the Salicylate Synthase (SaS) of Mab as an innovative molecular target for the development of inhibitors of siderophore production. Notably, Mab-SaS does not have any counterpart in human cells, making it an interesting candidate for drug discovery. Starting from the analysis of the binding of a series of furan-based derivatives, previously identified by our group as inhibitors of MbtI from M. tuberculosis (Mtb), we successfully selected the lead compound 1, exhibiting a strong activity against Mab-SaS (IC50 ≈ 5 µM). Computational studies characterized the key interactions between 1 and the enzyme, highlighting the important roles of Y387, G421, and K207, the latter being one of the residues involved in the first step of the catalytic reaction. These results support the hypothesis that 5-phenylfuran-2-carboxylic acids are also a promising class of Mab-SaS inhibitors, paving the way for the optimization and rational design of more potent derivatives. Full article
(This article belongs to the Special Issue Drug Targeting towards Fighting Pathogen Bacteria)
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14 pages, 2500 KiB  
Article
Exploring the Antimicrobial and Pharmacological Potential of NF22 as a Potent Inhibitor of E. coli DNA Gyrase: An In Vitro and In Silico Study
by Samman Munir, Mohsin Khurshid, Matloob Ahmad, Usman Ali Ashfaq and Magdi E. A. Zaki
Pharmaceutics 2022, 14(12), 2768; https://doi.org/10.3390/pharmaceutics14122768 - 10 Dec 2022
Cited by 2 | Viewed by 1292
Abstract
Toward the search for novel antimicrobial agents to control pathogenic E. coli-associated infections, a series of novel norfloxacin derivatives were screened for antimicrobial activities. The norfloxacin derivative, 1-ethyl-6-fluoro-7-(4-(2-(2-(3-hydroxybenzylidene)hydrazinyl)-2-oxoethyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (NF22) demonstrated excellent antibacterial activities against E. coli ATCC 25922 (MIC = 0.0625 [...] Read more.
Toward the search for novel antimicrobial agents to control pathogenic E. coli-associated infections, a series of novel norfloxacin derivatives were screened for antimicrobial activities. The norfloxacin derivative, 1-ethyl-6-fluoro-7-(4-(2-(2-(3-hydroxybenzylidene)hydrazinyl)-2-oxoethyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (NF22) demonstrated excellent antibacterial activities against E. coli ATCC 25922 (MIC = 0.0625 μg/mL) and MDR E. coli 1–3 (MIC = 1, 2 and 1 µg/mL). The time-kill kinetic studies have demonstrated that the NF22 was advantageous over norfloxacin and ciprofloxacin in killing the control and MDR E. coli strains. The checkerboard assay showed that NF22 in combination with tetracycline had a synergistic effect against the E. coli strains. The experimental findings are supported by molecular modeling studies on DNA gyrase, explaining the interactions involved for compound NF22, compared to norfloxacin and ciprofloxacin. Further, the compound was also evaluated for various pharmacokinetics (absorption, metabolism, distribution, toxicity and excretion) as well as drug-likeness properties. Our data have highlighted the potential of norfloxacin by restoring its efficacy against E. coli which could lead to the development of new antimicrobial agents. Full article
(This article belongs to the Special Issue Drug Targeting towards Fighting Pathogen Bacteria)
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15 pages, 2827 KiB  
Article
Cecropin A Improves the Antibacterial Activity of Hen Egg White Lysozyme against Challenging Salmonella enterica Serovars
by Hani A. Alhadrami, Ahmed M. Sayed, Hossam M. Hassan, Mostafa E. Rateb and Karim Abdelkader
Pharmaceutics 2022, 14(10), 2201; https://doi.org/10.3390/pharmaceutics14102201 - 16 Oct 2022
Viewed by 1548
Abstract
The prevalence of multidrug-resistant Salmonella enterica among animal- and plant-derived food products threatens global healthcare and economic sectors. Hen egg white lysozyme is widely exploited as a food preservative against Gram-positive pathogens. Nevertheless, its limited penetration of the outer membrane renders it ineffective [...] Read more.
The prevalence of multidrug-resistant Salmonella enterica among animal- and plant-derived food products threatens global healthcare and economic sectors. Hen egg white lysozyme is widely exploited as a food preservative against Gram-positive pathogens. Nevertheless, its limited penetration of the outer membrane renders it ineffective against Gram-negative bacteria. Herein, we present a safe and effective approach to facilitate HEWL access to peptidoglycan layers using cecropin A. In silico analysis of cecropin A peptide revealed an amphipathic α-helical peptide with potential outer membrane permeabilizing activity through its interaction with both hydrophobic and ionic stabilizing forces. Evaluation of HEWL/cecropin A combination showed a cecropin A dose-dependent bacterial count reduction up to 4.16 and 3.18 ± 0.26 log units against Salmonella enterica ATCC 35664 at the logarithmic and stationary growth phases, respectively. Moreover, the combination displayed antibacterial activity of 2.1 ± 0.31 and ~1 log-unit reductions against Salmonella enterica serovars Kentucky, Typhimurium, and Enteritidis, respectively, whereas Hato and Shangani were found irresponsive. The cytotoxicity assay revealed compatibility of cecropin A with oral epithelial cells. These observations suggest HEWL/cecropin A combination as an effective and safe alternative to lysozyme against Salmonella enterica. Full article
(This article belongs to the Special Issue Drug Targeting towards Fighting Pathogen Bacteria)
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Review

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40 pages, 5626 KiB  
Review
Fluoroquinolones Hybrid Molecules as Promising Antibacterial Agents in the Fight against Antibacterial Resistance
by Ioana-Andreea Lungu, Octavia-Laura Moldovan, Victoria Biriș and Aura Rusu
Pharmaceutics 2022, 14(8), 1749; https://doi.org/10.3390/pharmaceutics14081749 - 22 Aug 2022
Cited by 28 | Viewed by 5272
Abstract
The emergence of bacterial resistance has motivated researchers to discover new antibacterial agents. Nowadays, fluoroquinolones keep their status as one of the essential classes of antibacterial agents. The new generations of fluoroquinolones are valuable therapeutic tools with a spectrum of activity, including Gram-positive, [...] Read more.
The emergence of bacterial resistance has motivated researchers to discover new antibacterial agents. Nowadays, fluoroquinolones keep their status as one of the essential classes of antibacterial agents. The new generations of fluoroquinolones are valuable therapeutic tools with a spectrum of activity, including Gram-positive, Gram-negative, and atypical bacteria. This review article surveys the design of fluoroquinolone hybrids with other antibacterial agents or active compounds and underlines the new hybrids’ antibacterial properties. Antibiotic fluoroquinolone hybrids have several advantages over combined antibiotic therapy. Thus, some challenges related to joining two different molecules are under study. Structurally, the obtained hybrids may contain a cleavable or non-cleavable linker, an essential element for their pharmacokinetic properties and mechanism of action. The design of hybrids seems to provide promising antibacterial agents helpful in the fight against more virulent and resistant strains. These hybrid structures have proven superior antibacterial activity and less susceptibility to bacterial resistance than the component molecules. In addition, fluoroquinolone hybrids have demonstrated other biological effects such as anti-HIV, antifungal, antiplasmodic/antimalarial, and antitumor activity. Many fluoroquinolone hybrids are in various phases of clinical trials, raising hopes that new antibacterial agents will be approved shortly. Full article
(This article belongs to the Special Issue Drug Targeting towards Fighting Pathogen Bacteria)
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