Antibiotic Resistance Mechanisms and Their Potential Solutions

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 15 October 2024 | Viewed by 3999

Special Issue Editors


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Guest Editor
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: antibiotic resistance; molecular epidemiology; antimicrobial development
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, Taiwan
Interests: antimicrobial resistance mechanisms; bacterial genomics and gene regulation; antimicrobial-drug development
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Medical Laboratory Science, I-Shou University, Kaohsiung, Taiwan
Interests: antibiotic resistance; molecular epidemiology; antimicrobial development; bioactive materials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Due to the overconsumption of antibiotics, growing resistance has extensively limited their therapeutic options in clinical settings, such as resistance to carbapenems, colistin, methicillin, and vancomycin. Mechanistic studies on antibiotic resistance could potentially provide evidence for further research, including molecular docking for antibiotic development and control of the spreading resistance. Furthermore, the World Health Organization announced a priority list for antibiotic development in 2017, highlighting the severity of antibiotic resistance and the urgent need for novel antimicrobials.

In the current Special Issue, we study the efforts made to develop antibiotic-resistant mechanisms and potential therapeutic options/approaches to address this crisis. Our interests include but are not limited to extensively/multiple-drug-resistant Mycobacterium tuberculosis, carbapenem-resistant Gram-negative bacterium, vancomycin-resistant Enterococcus spp., methicillin-resistant Staphylococcus spp., clarithromycin-resistant Helicobacter pylori, fluoroquinolone-resistant Campylobacter spp. and Salmonella spp., and 3rd-generation cephalosporin-resistant Neisseria gonorrhoeae.

Prof. Dr. Sung-Pin Tseng
Dr. Cheng Yen Kao
Dr. Tsung-Ying Yang
Guest Editors

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Keywords

  • antibiotic resistance
  • antimicrobial development
  • molecular mechanism
  • priority for antibiotics
  • newly therapeutic approach

Published Papers (3 papers)

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Research

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14 pages, 7781 KiB  
Article
Enzymes with Lactonase Activity against Fungal Quorum Molecules as Effective Antifungals
by Elena Efremenko, Aysel Aslanli, Maksim Domnin, Nikolay Stepanov and Olga Senko
Biomolecules 2024, 14(3), 383; https://doi.org/10.3390/biom14030383 - 21 Mar 2024
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Abstract
Since the growing number of fungi resistant to the fungicides used is becoming a serious threat to human health, animals, and crops, there is a need to find other effective approaches in the eco-friendly suppression of fungal growth. One of the main mechanisms [...] Read more.
Since the growing number of fungi resistant to the fungicides used is becoming a serious threat to human health, animals, and crops, there is a need to find other effective approaches in the eco-friendly suppression of fungal growth. One of the main mechanisms of the development of resistance in fungi, as well as in bacteria, to antimicrobial agents is quorum sensing (QS), in which various lactone-containing compounds participate as signaling molecules. This work aimed to study the effectiveness of action of enzymes exhibiting lactonase activity against fungal signaling molecules. For this, the molecular docking method was used to estimate the interactions between these enzymes and different lactone-containing QS molecules of fungi. The catalytic characteristics of enzymes such as lactonase AiiA, metallo-β-lactamase NDM-1, and organophosphate hydrolase His6-OPH, selected for wet experiments based on the results of computational modeling, were investigated. QS lactone-containing molecules (butyrolactone I and γ-heptalactone) were involved in the experiments as substrates. Further, the antifungal activity of the enzymes was evaluated against various fungal and yeast cells using bioluminescent ATP-metry. The efficient hydrolysis of γ-heptalactone by all three enzymes and butyrolactone I by His6-OPH was demonstrated for the first time. The high antifungal efficacy of action of AiiA and NDM-1 against most of the tested fungal cells was revealed. Full article
(This article belongs to the Special Issue Antibiotic Resistance Mechanisms and Their Potential Solutions)
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15 pages, 3203 KiB  
Article
Norlobaridone Inhibits Quorum Sensing-Dependent Biofilm Formation and Some Virulence Factors in Pseudomonas aeruginosa by Disrupting Its Transcriptional Activator Protein LasR Dimerization
by Raya Soltane, Ahlam Alasiri, Mostafa N. Taha, Rehab H. Abd El-Aleam, Kawthar Saad Alghamdi, Mosad A. Ghareeb, Doaa El-Ghareeb Keshek, Susana M. Cardoso and Ahmed M. Sayed
Biomolecules 2023, 13(11), 1573; https://doi.org/10.3390/biom13111573 - 24 Oct 2023
Cited by 1 | Viewed by 1195
Abstract
In the present study, norlobaridone (NBD) was isolated from Parmotrema and then evaluated as a new potent quorum sensing (QS) inhibitor against Pseudomonas aeruginosa biofilm development. This phenolic natural product was found to reduce P. aeruginosa biofilm formation (64.6% inhibition) and its related [...] Read more.
In the present study, norlobaridone (NBD) was isolated from Parmotrema and then evaluated as a new potent quorum sensing (QS) inhibitor against Pseudomonas aeruginosa biofilm development. This phenolic natural product was found to reduce P. aeruginosa biofilm formation (64.6% inhibition) and its related virulence factors, such as pyocyanin and rhamnolipids (% inhibition = 61.1% and 55%, respectively). In vitro assays inhibitory effects against a number of known LuxR-type receptors revealed that NBD was able to specifically block P. aeruginosa’s LasR in a dose-dependent manner. Further molecular studies (e.g., sedimentation velocity and thermal shift assays) demonstrated that NBD destabilized LasR upon binding and damaged its functional quaternary structure (i.e., the functional dimeric form). The use of modelling and molecular dynamics (MD) simulations also allowed us to further understand its interaction with LasR, and how this can disrupt its dimeric form. Finally, our findings show that NBD is a powerful and specific LasR antagonist that should be widely employed as a chemical probe in QS of P. aeruginosa, providing new insights into LasR antagonism processes. The new discoveries shed light on the mysterious world of LuxR-type QS in this key opportunistic pathogen. Full article
(This article belongs to the Special Issue Antibiotic Resistance Mechanisms and Their Potential Solutions)
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Review

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14 pages, 1133 KiB  
Review
Boosting Fitness Costs Associated with Antibiotic Resistance in the Gut: On the Way to Biorestoration of Susceptible Populations
by Fernando Baquero, Jerónimo Rodríguez-Beltrán, Teresa M. Coque and Rosa del Campo
Biomolecules 2024, 14(1), 76; https://doi.org/10.3390/biom14010076 - 08 Jan 2024
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Abstract
The acquisition and expression of antibiotic resistance implies changes in bacterial cell physiology, imposing fitness costs. Many human opportunistic pathogenic bacteria, such as those causing urinary tract or bloodstream infections, colonize the gut. In this opinionated review, we will examine the various types [...] Read more.
The acquisition and expression of antibiotic resistance implies changes in bacterial cell physiology, imposing fitness costs. Many human opportunistic pathogenic bacteria, such as those causing urinary tract or bloodstream infections, colonize the gut. In this opinionated review, we will examine the various types of stress that these bacteria might suffer during their intestinal stay. These stresses, and their compensatory responses, probably have a fitness cost, which might be additive to the cost of expressing antibiotic resistance. Such an effect could result in a disadvantage relative to antibiotic susceptible populations that might replace the resistant ones. The opinion proposed in this paper is that the effect of these combinations of fitness costs should be tested in antibiotic resistant bacteria with susceptible ones as controls. This testing might provide opportunities to increase the bacterial gut stress boosting physiological biomolecules or using dietary interventions. This approach to reduce the burden of antibiotic-resistant populations certainly must be answered empirically. In the end, the battle against antibiotic resistance should be won by antibiotic-susceptible organisms. Let us help them prevail. Full article
(This article belongs to the Special Issue Antibiotic Resistance Mechanisms and Their Potential Solutions)
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