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Special Issue "Advances in Antibacterial Drug Discovery and Therapy"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 15 February 2019

Special Issue Editor

Guest Editor
Dr. Dianqing Sun

The Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii
Website | E-Mail
Phone: 001-808-933-2960
Interests: Organic and Medicinal Chemistry; Antibacterial and Anticancer Drug Discovery

Special Issue Information

Dear Colleagues,

On behalf of the Journal of Clinical Medicine (JCM) editorial team, we are delighted to present a new Special Issue on the topic of “Advances in Antibacterial Drug Discovery and Therapy”, Guest Edited by Dr. Dianqing Sun, from the University of Hawaii at Hilo, USA.

Bacterial infections caused by Mycobacterium tuberculosis and other clinically significant pathogenic bacteria pose growing and serious threats to global public health. This problem is further compounded by mounting antibacterial drug resistance, limited antimicrobial therapy options, and the overall lack of new antibacterial development by the pharmaceutical industry. According to the Centers for Disease Control and Prevention (CDC), in the United States alone, there are more than two million illnesses and 23,000 deaths every year resulting from antibiotic-resistant bacterial infections, with added healthcare costs of about 20 billion dollars. In addition, a 2013 CDC report assigned Clostridium difficile (C. difficile), carbapenem-resistant Enterobacteriaceae, and drug-resistant Neisseria gonorrhoeae into the antibiotic resistance “urgent threat” category. C. difficile remains the most common cause of hospital-acquired diarrhea and can lead to a life-threatening infection or inflammation, particularly among the elderly. In the US, C. difficile is responsible for about 500,000 cases of infections and approximately 15,000 deaths each year, with added healthcare costs of one billion dollars. Notably, for drug resistant and more difficult-to-treat organisms including some gram-negative pathogens, older, more toxic, and costly last-resort antibiotics are increasingly being used to combat these serious infections. As a result, superbugs resistant to the last-resort antibiotics have also been on the rise. Therefore, there is a significant need to develop the next generation of safe antibiotics with improved efficacy and antibacterial resistance profiles.

This Special Issue highlights some recent and historical advances in antibacterial drug discovery and development. Topics may include, but are not limited to, natural product antibacterial drug discovery, small molecule antimicrobial agents, target identification and validation, hit to lead and lead optimization, structure-based design, combination antibiotic therapy, and clinical practice guidelines.

Dr. Dianqing Sun
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 papers will be 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. Journal of Clinical Medicine 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 1000 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

  • antibacterial drug discovery and development
  • antimicrobial resistance
  • medicinal chemistry
  • structure–activity relationship
  • chemical synthesis
  • rational design
  • computational modeling
  • natural product drug discovery
  • bacterial therapy
  • clinical practice

Published Papers (3 papers)

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Research

Open AccessArticle Effects of 462 nm Light-Emitting Diode on the Inactivation of Escherichia coli and a Multidrug-Resistant by Tetracycline Photoreaction
J. Clin. Med. 2018, 7(9), 278; https://doi.org/10.3390/jcm7090278
Received: 13 August 2018 / Revised: 6 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
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Abstract
The adaptability of bacterial resistance to antibiotics contributes to its high efficiency during evolution. Tetracycline (TC) is a broad-spectrum antimicrobial agent. Chromatographic analyses and mass spectrometry were used to study the effects of the light illumination of a 462 nm light-emitting diode (LED)
[...] Read more.
The adaptability of bacterial resistance to antibiotics contributes to its high efficiency during evolution. Tetracycline (TC) is a broad-spectrum antimicrobial agent. Chromatographic analyses and mass spectrometry were used to study the effects of the light illumination of a 462 nm light-emitting diode (LED) on the conformational changes of TC in a phosphate buffer solution (PBS, pH 7.8). Especially, the inactivation of superoxide anion radicals (O2) and Escherichia coli (E. coli), including that of a multidrug-resistant E. coli (MDR E. coli), were investigated during the photolysis of TC. A photolysis product of TC (PPT) was generated in an alkaline solution after the illumination of a blue light. The mass spectra of PPT had characteristic ion signals in m/z 459, 445, and 249.1 Da. The PPT has the molecular formula of C22H22N2O9, and the exact mass is 458.44 g/mol. The inactivation of MDR E. coli is not significant with TC treatment. The drug-resistant ability of MDR E. coli has a less significant effect on PPT, and the changed conformation of TC retained the inactivation ability of MDR E. coli upon blue light photoreaction. With TC, illuminated by a blue light in a pH 7.8 PBS, O2 was generated from TC photolysis, which enhanced the inactivation of E. coli and MDR E. coli. A 96.6% inactivation rate of MDR E. coli was reached with TC under 2.0 mW/cm2 blue light illumination at 25 ± 3 °C for 120 min, and the effects of the TC-treated photoreaction on MDR E. coli viability repressed the growth of MDR E. coli by 4 to 5 logs. The present study of the blue light photoreaction of TC offers a new approach to the inactivation of MDR E. coli. Full article
(This article belongs to the Special Issue Advances in Antibacterial Drug Discovery and Therapy)
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Figure 1

Open AccessArticle Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations
J. Clin. Med. 2018, 7(8), 226; https://doi.org/10.3390/jcm7080226
Received: 23 July 2018 / Revised: 13 August 2018 / Accepted: 17 August 2018 / Published: 20 August 2018
Cited by 1 | PDF Full-text (1391 KB) | HTML Full-text | XML Full-text
Abstract
The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for
[...] Read more.
The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0–13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5'-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC50) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC50 value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure–activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections. Full article
(This article belongs to the Special Issue Advances in Antibacterial Drug Discovery and Therapy)
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Graphical abstract

Open AccessArticle Tobramycin-Linked Efflux Pump Inhibitor Conjugates Synergize Fluoroquinolones, Rifampicin and Fosfomycin against Multidrug-Resistant Pseudomonas aeruginosa
J. Clin. Med. 2018, 7(7), 158; https://doi.org/10.3390/jcm7070158
Received: 24 May 2018 / Revised: 12 June 2018 / Accepted: 19 June 2018 / Published: 22 June 2018
Cited by 1 | PDF Full-text (608 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, we examined the in vitro effect of tobramycin-efflux pump inhibitor (TOB-EPI) conjugates in combinations with fluoroquinolones, rifampicin and fosfomycin on the growth of multi-drug resistant (MDR) and extremely-drug resistant (XDR) Pseudomonas aeruginosa. The TOB-EPI conjugates include tobramycin covalently linked
[...] Read more.
In this study, we examined the in vitro effect of tobramycin-efflux pump inhibitor (TOB-EPI) conjugates in combinations with fluoroquinolones, rifampicin and fosfomycin on the growth of multi-drug resistant (MDR) and extremely-drug resistant (XDR) Pseudomonas aeruginosa. The TOB-EPI conjugates include tobramycin covalently linked to 1-(1-naphthylmethyl)-piperazine (NMP) (1), paroxetine (PAR) (2) and a dibasic peptide analogue of MC-04,124 (DBP) (3). Potent synergism was found for combinations of TOB-NMP (1), TOB-PAR (2) or TOB-DBP (3) with either fluoroquinolones (moxifloxacin, ciprofloxacin), rifampicin or fosfomycin against a panel of multidrug-resistant/extensively drug-resistant (MDR/XDR) P. aeruginosa clinical isolates. In the presence of ≤8 mg/L (6.1–7.2 µM) (≤¼ × MICadjuvant) concentration of the three conjugates, the MIC80 of moxifloxacin, ciprofloxacin, rifampicin and fosfomycin were dramatically reduced. Furthermore, the MIC80 of rifampicin (0.25–0.5 mg/L) and fosfomycin (8–16 mg/L) were reduced below their interpretative susceptibility breakpoints. Our data confirm the ability of TOB-NMP (1), TOB-PAR (2) and TOB-DBP (3) conjugates to strongly synergize with moxifloxacin, ciprofloxacin, rifampicin and fosfomycin against MDR/XDR P. aeruginosa. These synergistic combinations warrant further studies as there is an urgent need to develop new strategies to treat drug-resistant P. aeruginosa infections. Full article
(This article belongs to the Special Issue Advances in Antibacterial Drug Discovery and Therapy)
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Graphical abstract

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