New Insights in Antimicrobial Discovery

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 23767

Special Issue Editors


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Guest Editor
College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
Interests: infectious diseases; drug discovery from novel and unusual sources; nanotechnology
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Guest Editor
College of Arts and Sciences, American University of Sharjah, Sharjah 269999, United Arab Emirates
Interests: pathogens of the CNS; antimicrobial resistance; antimicrobial drug discovery

Special Issue Information

Dear Colleagues,

Infectious diseases are a leading cause of morbidity and mortality, killing more than 14 million people globally every year. Furthermore, the emergence of antimicrobial resistance presents a significant threat to human and animal health despite advances in antimicrobial discovery. This Special Issue seeks manuscript submissions on all aspects of antimicrobial discovery, comprising nanotechnology, antimicrobial peptides, and modification of existent drugs in the quest to treat rising infectious diseases. All submission types, such as original research manuscripts, short communications, and reviews, are appreciated.

Prof. Dr. Naveed Ahmed Khan
Prof. Dr. Ruqaiyyah Siddiqui 
Guest Editors

Manuscript Submission Information

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Keywords

  • antimicrobial discovery
  • novel molecules
  • nanoparticles
  • antimicrobial resistance
  • infectious diseases
  • drug discovery

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Published Papers (5 papers)

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Research

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12 pages, 3126 KiB  
Article
Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.
by Rubén L. Rodríguez-Expósito, Ines Sifaoui, María Reyes-Batlle, Sutherland K. Maciver, José E. Piñero and Jacob Lorenzo-Morales
Antibiotics 2022, 11(2), 280; https://doi.org/10.3390/antibiotics11020280 - 21 Feb 2022
Cited by 9 | Viewed by 2511
Abstract
Acanthamoeba is a ubiquitous opportunistic protozoan pathogen that is known to cause blinding keratitis and rare, but usually fatal, granulomatous encephalitis. The difficulty in treating infections and the toxicity issues of the current treatments emphasize the need to use alternative agents with amoebicidal [...] Read more.
Acanthamoeba is a ubiquitous opportunistic protozoan pathogen that is known to cause blinding keratitis and rare, but usually fatal, granulomatous encephalitis. The difficulty in treating infections and the toxicity issues of the current treatments emphasize the need to use alternative agents with amoebicidal activity. The aim of this study was to evaluate the in vitro antiamoebic activity of three third-generation statins—cerivastatin, pitavastatin and rosuvastatin—against both cysts and trophozoites of the following four strains of Acanthamoeba: A. castellanii Neff, A. polyphaga, A. griffini and A. quina. Furthermore, programmed cell death (PCD) induction traits were evaluated by measuring chromatin condensation, damages at the mitochondrial level, production of reactive oxygen species (ROS) and the distribution of actin cytoskeleton fibers. Acanthamoeba castellanii Neff was the strain most sensitive to all the statins, where cerivastatin showed the lowest amoebicidal activity for both trophozoite and cyst forms (0.114 ± 0.050 and 0.704 ± 0.129 µM, respectively). All the statins were able to cause DNA condensation, collapse in the mitochondrial membrane potential and a reduction in ATP level production, and disorganization of the total actin fibers in the cytoskeleton of all the evaluated Acanthamoeba strains. Our results showed that the tested statins were able to induce PCD compatible events in the treated amoebae, including chromatin condensation, collapse in the mitochondrial potential and ATP levels, cytoskeleton disassembly and ROS generation. Full article
(This article belongs to the Special Issue New Insights in Antimicrobial Discovery)
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14 pages, 1115 KiB  
Article
Novel Plant-Based Metabolites as Disinfectants against Acanthamoeba castellanii
by Ruqaiyyah Siddiqui, Noor Akbar, Bushra Khatoon, Muhammad Kawish, Muhammad Shaiq Ali, Muhammad Raza Shah and Naveed Ahmed Khan
Antibiotics 2022, 11(2), 248; https://doi.org/10.3390/antibiotics11020248 - 14 Feb 2022
Cited by 11 | Viewed by 3156
Abstract
Due to global warming, coupled with global water shortages and the reliance of the public on household water tanks, especially in developing countries, it is anticipated that infections caused by free-living amoebae such as Acanthamoeba will rise. Thus, the development of novel disinfectant(s) [...] Read more.
Due to global warming, coupled with global water shortages and the reliance of the public on household water tanks, especially in developing countries, it is anticipated that infections caused by free-living amoebae such as Acanthamoeba will rise. Thus, the development of novel disinfectant(s) which can target pathogenic free-living amoebae effectively is warranted. Herein, we extracted and isolated several plant-based secondary metabolites as novel disinfectants for use against pathogenic Acanthamoeba. The identity of the compounds was confirmed by nuclear magnetic resonance and tested for antiamoebic activities against clinical isolate of A. castellanii, belonging to the T4 genotype. Amoebicidal assays revealed that the compounds tested showed antiamoebic properties. Betulinic acid and betulin exhibited parasite killing of more than 65%. When tested against the cyst stage, betulinic acid, betulin, and vanillic acid inhibited both encystation and excystation processes. Furthermore, the plant-based metabolites significantly inhibited the binding capability of A. castellanii to host cells. Finally, most of the tested compounds displayed minimal cytotoxic activities against human cells and noticeably perturbed amoeba-mediated host cell cytotoxicity. Notably, both alkaloid and betulinic acid showed 20% cytotoxic effects, whereas betulin and lupeol had cytotoxic effects of 24% and 30%, respectively. Overall, our findings indicate that plant-based natural compounds demonstrate anti-Acanthamoebic properties, and they have potential candidates for water disinfectants or contact lens disinfecting solutions, as well as possible therapeutic drugs against Acanthamoeba infections. Full article
(This article belongs to the Special Issue New Insights in Antimicrobial Discovery)
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Review

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25 pages, 4937 KiB  
Review
The Association between Biofilm Formation and Antimicrobial Resistance with Possible Ingenious Bio-Remedial Approaches
by Yogesh Dutt, Ruby Dhiman, Tanya Singh, Arpana Vibhuti, Archana Gupta, Ramendra Pati Pandey, V. Samuel Raj, Chung-Ming Chang and Anjali Priyadarshini
Antibiotics 2022, 11(7), 930; https://doi.org/10.3390/antibiotics11070930 - 11 Jul 2022
Cited by 49 | Viewed by 6856
Abstract
Biofilm has garnered a lot of interest due to concerns in various sectors such as public health, medicine, and the pharmaceutical industry. Biofilm-producing bacteria show a remarkable drug resistance capability, leading to an increase in morbidity and mortality. This results in enormous economic [...] Read more.
Biofilm has garnered a lot of interest due to concerns in various sectors such as public health, medicine, and the pharmaceutical industry. Biofilm-producing bacteria show a remarkable drug resistance capability, leading to an increase in morbidity and mortality. This results in enormous economic pressure on the healthcare sector. The development of biofilms is a complex phenomenon governed by multiple factors. Several attempts have been made to unravel the events of biofilm formation; and, such efforts have provided insights into the mechanisms to target for the therapy. Owing to the fact that the biofilm-state makes the bacterial pathogens significantly resistant to antibiotics, targeting pathogens within biofilm is indeed a lucrative prospect. The available drugs can be repurposed to eradicate the pathogen, and as a result, ease the antimicrobial treatment burden. Biofilm formers and their infections have also been found in plants, livestock, and humans. The advent of novel strategies such as bioinformatics tools in treating, as well as preventing, biofilm formation has gained a great deal of attention. Development of newfangled anti-biofilm agents, such as silver nanoparticles, may be accomplished through omics approaches such as transcriptomics, metabolomics, and proteomics. Nanoparticles’ anti-biofilm properties could help to reduce antimicrobial resistance (AMR). This approach may also be integrated for a better understanding of biofilm biology, guided by mechanistic understanding, virtual screening, and machine learning in silico techniques for discovering small molecules in order to inhibit key biofilm regulators. This stimulated research is a rapidly growing field for applicable control measures to prevent biofilm formation. Therefore, the current article discusses the current understanding of biofilm formation, antibiotic resistance mechanisms in bacterial biofilm, and the novel therapeutic strategies to combat biofilm-mediated infections. Full article
(This article belongs to the Special Issue New Insights in Antimicrobial Discovery)
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16 pages, 1354 KiB  
Review
Epigenetic-Mediated Antimicrobial Resistance: Host versus Pathogen Epigenetic Alterations
by Jibran Sualeh Muhammad, Naveed Ahmed Khan, Sutherland K. Maciver, Ahmad M. Alharbi, Hasan Alfahemi and Ruqaiyyah Siddiqui
Antibiotics 2022, 11(6), 809; https://doi.org/10.3390/antibiotics11060809 - 16 Jun 2022
Cited by 9 | Viewed by 4390
Abstract
Since the discovery of antibiotics, humans have been benefiting from them by decreasing the morbidity and mortality associated with bacterial infections. However, in the past few decades, misuse of antibiotics has led to the emergence of bacterial infections resistant to multiple drugs, a [...] Read more.
Since the discovery of antibiotics, humans have been benefiting from them by decreasing the morbidity and mortality associated with bacterial infections. However, in the past few decades, misuse of antibiotics has led to the emergence of bacterial infections resistant to multiple drugs, a significant health concern. Bacteria exposed to inappropriate levels of antibiotics lead to several genetic changes, enabling them to survive in the host and become more resistant. Despite the understanding and targeting of genetic-based biochemical changes in the bacteria, the increasing levels of antibiotic resistance are not under control. Many reports hint at the role of epigenetic modifications in the bacterial genome and host epigenetic reprogramming due to interaction with resistant pathogens. Epigenetic changes, such as the DNA-methylation-based regulation of bacterial mutation rates or bacteria-induced histone modification in human epithelial cells, facilitate its long-term survival. In this review article, epigenetic changes leading to the development of antibiotic resistance in clinically relevant bacteria are discussed. Additionally, recent lines of evidence focusing on human host epigenetic changes due to the human–pathogen interactions are presented. As genetic mechanisms cannot explain the transient nature of antimicrobial resistance, we believe that epigenetics may provide new frontiers in antimicrobial discovery. Full article
(This article belongs to the Special Issue New Insights in Antimicrobial Discovery)
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20 pages, 4522 KiB  
Review
Emerging Concern with Imminent Therapeutic Strategies for Treating Resistance in Biofilm
by Ramendra Pati Pandey, Riya Mukherjee and Chung-Ming Chang
Antibiotics 2022, 11(4), 476; https://doi.org/10.3390/antibiotics11040476 - 2 Apr 2022
Cited by 17 | Viewed by 5407
Abstract
Biofilm production by bacteria is presumed to be a survival strategy in natural environments. The production of biofilms is known to be influenced by a number of factors. This paper has precisely elaborated on the different factors that directly influence the formation of [...] Read more.
Biofilm production by bacteria is presumed to be a survival strategy in natural environments. The production of biofilms is known to be influenced by a number of factors. This paper has precisely elaborated on the different factors that directly influence the formation of biofilm. Biofilm has serious consequences for human health, and a variety of infections linked to biofilm have emerged, rapidly increasing the statistics of antimicrobial resistance, which is a global threat. Additionally, to combat resistance in biofilm, various approaches have been developed. Surface modifications, physical removal, and the use of nanoparticles are the recent advances that have enabled drug discovery for treating various biofilm-associated infections. Progress in nanoparticle production has led to the development of a variety of biofilm-fighting strategies. We focus on the present and future therapeutic options that target the critical structural and functional characteristics of microbial biofilms, as well as drug tolerance mechanisms, such as the extracellular matrix, in this review. Full article
(This article belongs to the Special Issue New Insights in Antimicrobial Discovery)
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