‘Non-traditional’ Antimicrobial Approaches to Combat Antimicrobial Resistance

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 2458

Special Issue Editor


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Guest Editor
Europa Point Campus, University of Gibraltar, Gibraltar, MI, USA
Interests: antimicrobial resistance (AMR); public health; non-traditional antimicrobial approaches; superbug

Special Issue Information

Dear Colleagues,

For years, the threat of antimicrobial resistance (AMR) has been looming over the global population, threatening the security of public health. With the advent of numerous multidrug-resistant organisms (MDROs) that have evolved to resist a multiplicity of conventionally used antimicrobials, it is now vital that we develop strategies to combat infectious diseases. The purpose of this Special Issue, entitled ‘“Non-traditional” antimicrobial approaches to combat antimicrobial resistance’, is to compile a collection of manuscripts that are involved with developing novel and highly effective therapeutics that aim to adjust the clinical paradigm and quell the negative effects of AMR. Research into novel light-based antimicrobial approaches, phage therapeutics, peptide nucleic acids, antimicrobial peptides, probiotics, plant-based antimicrobials, combination therapies, boosting conventional antimicrobials (such as with the use of adjuvants), and all other non-traditional methods focused on treating infectious diseases are welcome. 

Dr. Leon G. Leanse
Guest Editor

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Keywords

  • antimicrobial resistance
  • non-traditional antimicrobial technologies
  • antibiotics

Published Papers (2 papers)

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22 pages, 2025 KiB  
Article
Short Antimicrobial Peptide Derived from the Venom Gland Transcriptome of Pamphobeteus verdolaga Increases Gentamicin Susceptibility of Multidrug-Resistant Klebsiella pneumoniae
by Cristian Salinas-Restrepo, Ana María Naranjo-Duran, Juan Quintana, Julio Bueno, Fanny Guzman, Lina M. Hoyos Palacio and Cesar Segura
Antibiotics 2024, 13(1), 6; https://doi.org/10.3390/antibiotics13010006 - 20 Dec 2023
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Abstract
Infectious diseases account for nine percent of annual human deaths, and the widespread emergence of antimicrobial resistances threatens to significantly increase this number in the coming decades. The prospect of antimicrobial peptides (AMPs) derived from venomous animals presents an interesting alternative for developing [...] Read more.
Infectious diseases account for nine percent of annual human deaths, and the widespread emergence of antimicrobial resistances threatens to significantly increase this number in the coming decades. The prospect of antimicrobial peptides (AMPs) derived from venomous animals presents an interesting alternative for developing novel active pharmaceutical ingredients (APIs). Small, cationic and amphiphilic peptides were predicted from the venom gland transcriptome of Pamphobeteus verdolaga using a custom database of the arthropod’s AMPs. Ninety-four candidates were chemically synthesized and screened against ATCC® strains of Escherichia coli and Staphylococcus aureus. Among them, one AMP, named PvAMP66, showed broad-spectrum antimicrobial properties with selectivity towards Gram-negative bacteria. It also exhibited activity against Pseudomonas aeruginosa, as well as both an ATCC® and a clinically isolated multidrug-resistant (MDR) strain of K. pneumoniae. The scanning electron microscopy analysis revealed that PvAMP66 induced morphological changes of the MDR K. pneumoniae strain suggesting a potential “carpet model” mechanism of action. The isobologram analysis showed an additive interaction between PvAMP66 and gentamicin in inhibiting the growth of MDR K. pneumoniae, leading to a ten-fold reduction in gentamicin’s effective concentration. A cytotoxicity against erythrocytes or peripheral blood mononuclear cells was observed at concentrations three to thirteen-fold higher than those exhibited against the evaluated bacterial strains. This evidence suggests that PvAMP66 can serve as a template for the development of AMPs with enhanced activity and deserves further pre-clinical studies as an API in combination therapy. Full article
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6 pages, 187 KiB  
Brief Report
NRX-101 (D-Cycloserine + Lurasidone) Is Active against Drug-Resistant Urinary Pathogens In Vitro
by Michael T. Sapko, Michael Manyak, Riccardo Panicucci and Jonathan C. Javitt
Antibiotics 2024, 13(4), 308; https://doi.org/10.3390/antibiotics13040308 - 28 Mar 2024
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Abstract
D-Cycloserine (DCS) is a broad-spectrum antibiotic that is currently FDA-approved to treat tuberculosis (TB) disease and urinary tract infection (UTI). Despite numerous reports showing good clinical efficacy, DCS fell out of favor as a UTI treatment because of its propensity to cause side [...] Read more.
D-Cycloserine (DCS) is a broad-spectrum antibiotic that is currently FDA-approved to treat tuberculosis (TB) disease and urinary tract infection (UTI). Despite numerous reports showing good clinical efficacy, DCS fell out of favor as a UTI treatment because of its propensity to cause side effects. NRX-101, a fixed-dose combination of DCS and lurasidone, has been awarded Qualified Infectious Disease Product and Fast Track Designation by the FDA. In this study, we tested NRX-101 against the urinary tract pathogens Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii in cation-adjusted Mueller–Hinton broth (caMHB) and artificial urine media (AUM). Several strains were multidrug resistant. Test compounds were serially diluted in broth/media. Minimum inhibitory concentration (MIC) was defined as the lowest concentration of the test compound at which no bacterial growth was observed. DCS exhibited antibacterial efficacy against all strains tested while lurasidone did not appreciably affect the antibacterial action of DCS in vitro. In AUM, the MICs ranged from 128 to 512 mcg/mL for both DCS and NRX-101. In caMHB, MICs ranged from 8 to 1024 mcg/mL for NRX-101 and 32 to 512 mcg/mL for DCS alone. Our data confirm that DCS has antibacterial activity against reference and drug-resistant urinary pathogens. Furthermore, lurasidone does not interfere with DCS’s antimicrobial action in vitro. These results support the clinical development of NRX-101 as a treatment for complicated urinary tract infections. Full article
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