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Biomedicines
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Research of Molecules to Fight Antimicrobial Resistance
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Research of Molecules to Fight Antimicrobial Resistance

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 16803

Special Issue Editors

Dr. Maria Letizia Barreca

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy
Interests: medicinal chemistry; computer-aided drug discovery; anti-infective and neurodegenerative diseases; cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Stefano Sabatini

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Università degli Studi di Perugia, via del Liceo 1, 06123 Perugia, Italy
Interests: medicinal chemistry; rational drug design; antibacterial agents; antimicrobial resistance; drug-resistant pathogens; natural products; drug repurposing; antimicrobial resistance breakers; efflux pump inhibitors
Special Issues, Collections and Topics in MDPI journals
Dr. Andrea Astolfi

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy
Interests: medicinal chemistry; computer-aided drug discovery; anti-infective agents; kinase inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

WHO has declared antimicrobial resistance (AMR) as one of the top 10 global public health problems of the 21st century that threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses, and fungi which are no longer susceptible to common medicines. Classically, there are two main strategies to enhance the discovery of effective antimicrobial agents: drug repurposing or identifying novel chemical entities throughout the drug discovery pipeline, from target identification to clinical trials.

To be more specific, there is a growing interest in targeting non-essential targets (e.g. beta-lactamases, efflux pumps, and virulence factors) using adjuvants antibiotics or antimicrobial resistance breakers (ARBs), opening up the opportunity to limit or overcome the occurrence of resistance strains. Furthermore, anti-biofilm agents show promise for future antimicrobial treatments, as one of mechanisms of resistance used by microorganisms is the formation of biofilms, which protect them from attack by the host immune system and medical treatment.

In this Special Issue, entitled “Research of Molecules to Fight Antimicrobial Resistance”, high-quality reviews and original research articles centered around the identification of molecules to fight antimicrobial resistance, as well as on computational, structural, and functional studies aimed at increasing knowledge on this robust topic, are welcome.

Dr. Maria Letizia Barreca
Dr. Stefano Sabatini
Dr. Andrea Astolfi
Guest Editors

Manuscript Submission Information

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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. Biomedicines 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 2600 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 resistance
  • small molecules
  • drug design
  • computer-aided drug discovery
  • drug repurposing
  • non-essential targets
  • antimicrobial resistance breakers
  • anti-biofilm agents
  • efflux pump inhibitors

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Published Papers (6 papers)

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Research

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14 pages, 1394 KiB  
Article
HIV-1 Disease Progression and Drug Resistance Mutations among Children on First-Line Antiretroviral Therapy in Ethiopia
by Yimam Getaneh, Fentabil Getnet, Feng Ning, Abdur Rashid, Lingjie Liao, Feng Yi and Yiming Shao
Biomedicines 2023, 11(8), 2293; https://doi.org/10.3390/biomedicines11082293 - 18 Aug 2023
Cited by 4 | Viewed by 1945
Abstract
Background: High rates of disease progression and HIV drug resistance (HIVDR) among adults taking highly active antiretroviral treatment (HAART) in Sub-Saharan Africa were previously documented. However, children were generally not considered despite their greater risk. Hence, this study was aimed to evaluate HIV-1 [...] Read more.
Background: High rates of disease progression and HIV drug resistance (HIVDR) among adults taking highly active antiretroviral treatment (HAART) in Sub-Saharan Africa were previously documented. However, children were generally not considered despite their greater risk. Hence, this study was aimed to evaluate HIV-1 disease progression and drug resistance mutation among children on first-line antiretroviral therapy in Ethiopia. Method: A longitudinal study was conducted among 551 HIV-positive children (<15 years old) recruited between 2017 and 2019 at 40 antiretroviral treatment delivery sites in Ethiopia. Disease progression was retrospectively measured over a 12-year (2007–2019) follow-up as the progress towards immunosuppression. Two consecutive viral load (VL) tests were conducted in 6-month intervals to assess virologic failure (VF). For children with VF, HIV-1 genotyping and sequencing was performed for the pol gene region using in-house assay validated at the Chinese Center for Disease Control and Prevention, and the Stanford HIVDB v9.0 algorithm was used for identification of drug resistance mutations. The Kaplan–Meier analysis and Cox proportional hazards regression model were used to estimate the rate and predictors of disease progression, respectively. Results: The disease progression rate was 6.3 per 100 person-years-observation (95% CI = 4.21–8.53). Overall immunosuppression (CD4 count < 200 cells/mm3) during the 12-year follow-up was 11.3% (95% CI = 7.5–15.1). Immunosuppression was significantly increased as of the mean duration of 10.5 (95% CI = 10.1–10.8) years (38.2%) to 67.8% at 12 years (p < 0.001). Overall, 14.5% had resistance to at least one drug, and 6.2% had multi-drug resistance. A resistance of 67.8% was observed among children with VF. Resistance to non-nucleotide reverse transcriptase inhibitors (NNRTI) and nucleotide reverse transcriptase inhibitors (NRTI) drugs were 11.4% and 10.1%, respectively. Mutations responsible for NRTI resistance were M184V (30.1%), K65R (12.1%), and D67N (5.6%). Moreover, NNRTI-associated mutations were K103N (14.8%), Y181C (11.8%), and G190A (7.7%). Children who had a history of opportunistic infection [AHR (95% CI) = 3.4 (1.8–6.2)], vitamin D < 20 ng/mL [AHR (95% CI) = 4.5 (2.1–9.9)], drug resistance [AHR (95% CI) = 2.2 (1.4–3.6)], and VF [AHR (95% CI) = 2.82 (1.21, 3.53)] had a higher hazard of disease progression; whereas, being orphan [AOR (95% CI) = 1.8 (1.2–3.1)], history of drug substitution [(AOR (95% CI) = 4.8 (2.1–6.5), hemoglobin < 12 mg/dL [AOR (95% CI) = 1.2 (1.1–2.1)] had higher odds of developing drug resistance. Conclusions: Immunosuppression was increasing over time and drug resistance was also substantially high. Enhancing routine monitoring of viral load and HIVDR and providing a vitamin-D supplement during clinical management could help improve the immunologic outcome. Limiting HAART substitution is also crucial for children taking HAART in Ethiopia. Full article
(This article belongs to the Special Issue Research of Molecules to Fight Antimicrobial Resistance)
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15 pages, 7350 KiB  
Article
Padina boergesenii-Mediated Copper Oxide Nanoparticles Synthesis, with Their Antibacterial and Anticancer Potential
by Thirupathi Balaji, Chethakkad Manikkan Manushankar, Khalid A. Al-Ghanim, Chinnaperumal Kamaraj, Durairaj Thirumurugan, Sundaram Thanigaivel, Marcello Nicoletti, Nadezhda Sachivkina and Marimuthu Govindarajan
Biomedicines 2023, 11(8), 2285; https://doi.org/10.3390/biomedicines11082285 - 17 Aug 2023
Cited by 14 | Viewed by 2618
Abstract
The utilization of nanoparticles derived from algae has generated increasing attention owing to their environmentally sustainable characteristics and their capacity to interact harmoniously with biologically active metabolites. The present study utilized P. boergesenii for the purpose of synthesizing copper oxide nanoparticles (CuONPs), which [...] Read more.
The utilization of nanoparticles derived from algae has generated increasing attention owing to their environmentally sustainable characteristics and their capacity to interact harmoniously with biologically active metabolites. The present study utilized P. boergesenii for the purpose of synthesizing copper oxide nanoparticles (CuONPs), which were subsequently subjected to in vitro assessment against various bacterial pathogens and cancer cells A375. The biosynthesized CuONPs were subjected to various analytical techniques including FTIR, XRD, HRSEM, TEM, and Zeta sizer analyses in order to characterize their stability and assess their size distribution. The utilization of Fourier Transform Infrared (FTIR) analysis has provided confirmation that the algal metabolites serve to stabilize the CuONPs and function as capping agents. The X-ray diffraction (XRD) analysis revealed a distinct peak associated with the (103) plane, characterized by its sharpness and high intensity, indicating its crystalline properties. The size of the CuONPs in the tetragonal crystalline structure was measured to be 76 nm, and they exhibited a negative zeta potential. The biological assay demonstrated that the CuONPs exhibited significant antibacterial activity when tested against both Bacillus subtilis and Escherichia coli. The cytotoxic effects of CuONPs and cisplatin, when tested at a concentration of 100 µg/mL on the A375 malignant melanoma cell line, were approximately 70% and 95%, respectively. The CuONPs that were synthesized demonstrated significant potential in terms of their antibacterial properties and their ability to inhibit the growth of malignant melanoma cells. Full article
(This article belongs to the Special Issue Research of Molecules to Fight Antimicrobial Resistance)
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8 pages, 1278 KiB  
Communication
In Vitro Activity of Eravacycline against Carbapenemase-Producing Gram-Negative Bacilli Clinical Isolates in Central Poland
by Małgorzata Brauncajs, Filip Bielec, Anna Macieja and Dorota Pastuszak-Lewandoska
Biomedicines 2023, 11(7), 1784; https://doi.org/10.3390/biomedicines11071784 - 21 Jun 2023
Cited by 8 | Viewed by 2069
Abstract
Eravacycline is a novel antibiotic of the tetracycline class with activity against a broad spectrum of clinically significant bacteria, including multi-drug-resistant organisms. For this reason, it may be an alternative to treating critical infections of this etiology. We aimed to assess the in [...] Read more.
Eravacycline is a novel antibiotic of the tetracycline class with activity against a broad spectrum of clinically significant bacteria, including multi-drug-resistant organisms. For this reason, it may be an alternative to treating critical infections of this etiology. We aimed to assess the in vitro effectiveness of eravacycline to carbapenemase-producing Gram-negative bacilli clinical isolates identified in hospitals in Łódź, Poland. We analyzed 102 strains producing KPC, MBL, OXA-48, GES, and other carbapenemases. Eravacycline susceptibility was determined following the EUCAST guidelines. The highest susceptibility was found in KPC (73%) and MBL (59%) strains. Our results confirmed in vitro the efficacy of this drug against carbapenem-resistant strains. However, eravacycline has been indicated only for treating complicated intra-abdominal infections, significantly limiting its use. This aspect should be further explored to expand the indications for using eravacycline supported by evidence-based medicine. Eravacycline is one of the drugs that could play a role in reducing the spread of multidrug-resistant microorganisms. Full article
(This article belongs to the Special Issue Research of Molecules to Fight Antimicrobial Resistance)
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13 pages, 4454 KiB  
Article
Synthesis and Characterization of Mithun (Bos frontalis) Urine-Based Antibacterial Copper Oxide Nanoparticles
by Khriebu Bizo Pelesinuo, Govindharajan Sattanathan, Nazrul Haque, Khalid A. Al-Ghanim, Marcello Nicoletti, Nadezhda Sachivkina and Marimuthu Govindarajan
Biomedicines 2023, 11(6), 1690; https://doi.org/10.3390/biomedicines11061690 - 11 Jun 2023
Cited by 4 | Viewed by 2142
Abstract
The increased prevalence of disease, mortality, and antibiotic resistance among aquatic microorganisms has renewed interest in non-conventional disease prevention and control approaches. Nanoparticles present several benefits in aquaculture and hold significant potential for controlling both human and animal infections. This study reports on [...] Read more.
The increased prevalence of disease, mortality, and antibiotic resistance among aquatic microorganisms has renewed interest in non-conventional disease prevention and control approaches. Nanoparticles present several benefits in aquaculture and hold significant potential for controlling both human and animal infections. This study reports on the antibacterial properties of green copper oxide nanoparticles (CuO NPs) synthesized from the urine of Mithun (MU) (Bos frontalis). In addition, an array of analytical techniques, including scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-visible spectroscopy (UV), and Fourier transform infrared spectroscopy (FTIR), were employed to investigate the synthesized MU-CuO nanoparticles. Aeromonas hydrophila and Aeromonas veronii, two bacterial fish pathogens known to cause severe infectious diseases in fish, were tested for their antibacterial efficacy against MU-CuO NPs. At 100 µg/mL, MU-CuO NPs exhibit enhanced antibacterial efficacy against two bacterial pathogens commonly found in fish. Applications in aquaculture may be looked at given that MU-CuO NPs showed greater antibacterial activity. Full article
(This article belongs to the Special Issue Research of Molecules to Fight Antimicrobial Resistance)
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18 pages, 4765 KiB  
Article
Terminalia chebula-Assisted Silver Nanoparticles: Biological Potential, Synthesis, Characterization, and Ecotoxicity
by Munusamy Tharani, Shanmugam Rajeshkumar, Khalid A. Al-Ghanim, Marcello Nicoletti, Nadezhda Sachivkina and Marimuthu Govindarajan
Biomedicines 2023, 11(5), 1472; https://doi.org/10.3390/biomedicines11051472 - 18 May 2023
Cited by 20 | Viewed by 2776
Abstract
In the current research, an aqueous extract of Terminalia chebula fruit was used to produce silver nanoparticles (Ag NPs) in a sustainable manner. UV-visible spectrophotometry, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were used to characterize the synthesized nanoparticles. Synthesized Ag [...] Read more.
In the current research, an aqueous extract of Terminalia chebula fruit was used to produce silver nanoparticles (Ag NPs) in a sustainable manner. UV-visible spectrophotometry, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were used to characterize the synthesized nanoparticles. Synthesized Ag NPs were detected since their greatest absorption peak was seen at 460 nm. The synthesized Ag NPs were spherical and had an average size of about 50 nm, with agglomerated structures, as shown via SEM and TEM analyses. The biological activities of the synthesized Ag NPs were evaluated in terms of their antibacterial and antioxidant properties, as well as protein leakage and time-kill kinetics assays. The results suggest that the green synthesized Ag NPs possess significant antibacterial and antioxidant activities, making them a promising candidate for therapeutic applications. Furthermore, the study also evaluated the potential toxicological effects of the Ag NPs using zebrafish embryos as a model organism. The findings indicate that the synthesized Ag NPs did not induce any significant toxic effects on zebrafish embryos, further supporting their potential as therapeutic agents. In conclusion, the environmentally friendly production of Ag NPs using the extract from T. chebula is a promising strategy for discovering novel therapeutic agents with prospective uses in biomedicine. Full article
(This article belongs to the Special Issue Research of Molecules to Fight Antimicrobial Resistance)
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Review

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17 pages, 1842 KiB  
Review
Inhibition of Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily in Bacterial Pathogens
by Manuel F. Varela, Jerusha Stephen, Deeksha Bharti, Manjusha Lekshmi and Sanath Kumar
Biomedicines 2023, 11(5), 1448; https://doi.org/10.3390/biomedicines11051448 - 15 May 2023
Cited by 13 | Viewed by 4277
Abstract
Bacterial pathogens resistant to multiple structurally distinct antimicrobial agents are causative agents of infectious disease, and they thus constitute a serious concern for public health. Of the various bacterial mechanisms for antimicrobial resistance, active efflux is a well-known system that extrudes clinically relevant [...] Read more.
Bacterial pathogens resistant to multiple structurally distinct antimicrobial agents are causative agents of infectious disease, and they thus constitute a serious concern for public health. Of the various bacterial mechanisms for antimicrobial resistance, active efflux is a well-known system that extrudes clinically relevant antimicrobial agents, rendering specific pathogens recalcitrant to the growth-inhibitory effects of multiple drugs. In particular, multidrug efflux pump members of the major facilitator superfamily constitute central resistance systems in bacterial pathogens. This review article addresses the recent efforts to modulate these antimicrobial efflux transporters from a molecular perspective. Such investigations can potentially restore the clinical efficacy of infectious disease chemotherapy. Full article
(This article belongs to the Special Issue Research of Molecules to Fight Antimicrobial Resistance)
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