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Biomedicines
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Antibiotic Resistance in Biomedicines
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Antibiotic Resistance in Biomedicines

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 13479

Special Issue Editors

Dr. María Soledad Ramírez

E-Mail Website
Guest Editor
Department of Biological Science, California State University Fullerton, 800 N State College Blvd, Fullerton, CA 92831, USA
Interests: antibiotic resistance; infectious diseases; pathogenicity
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marcelo E. Tolmasky

E-Mail Website
Guest Editor
Department of Biological Science, California State University Fullerton, 800 N State College Blvd, Fullerton, CA 92831, USA
Interests: bacterial virulence; antibiotic resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotic resistance is now recognized as a major threat to human health, and it is considered a silent epidemic in the making. The rise of multidrug-resistant bacterial pathogens not only complicates the treatment of infectious diseases but also threatens medical procedures such as surgery, transplants, orthopedic implants, or chemotherapy, which depend on the prevention of infection. These routine procedures could become impossible if infection cannot be prevented using antibiotics. The fight against the rise and dissemination of multidrug-resistant bacteria must be tackled urgently, and it must be multidimensional. Public health measures must be taken to prevent an acceleration of bacterial acquisition of resistance to antibiotics in use. Research must be geared toward designing new classes of antibiotics and adjuvants that can overcome resistance to those in use. Multiple disciplines must come together to solve, or at least manage, this growing health emergency. This Special Issue will include multidisciplinary articles describing structural, genetic, and biochemical/biophysical research on basic mechanisms of drug resistance and their horizontal dissemination, epidemiology, strategies to reverse resistance using adjuvants, and approaches to reduce the impact of resistance.

Dr. María Soledad Ramírez
Prof. Dr. Marcelo E. Tolmasky
Guest Editors

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 submissions that pass pre-check are 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. 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

antibiotics resistance; novel therapeutic strategies; multidrug-resistant bacteria; horizontal dissemination; adjuvants; pathogens

Published Papers (4 papers)

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Research

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14 pages, 3169 KiB  
Article
Novel Genetically Engineered Probiotics for Targeted Elimination of Pseudomonas aeruginosa in Intestinal Colonization
by Hyun Kim, Ju Hye Jang, In Young Jung, Ha Rang Kim and Ju Hyun Cho
Biomedicines 2023, 11(10), 2645; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11102645 - 27 Sep 2023
Viewed by 1094
Abstract
The intestinal carriage rates of Pseudomonas aeruginosa are notably elevated in immunosuppressed individuals and hospitalized patients, increasing the risk of infection and antibiotic-associated diarrhea. A potential solution to this issue lies in autonomous antibacterial therapy, remaining inactive until a pathogen is detected, and [...] Read more.
The intestinal carriage rates of Pseudomonas aeruginosa are notably elevated in immunosuppressed individuals and hospitalized patients, increasing the risk of infection and antibiotic-associated diarrhea. A potential solution to this issue lies in autonomous antibacterial therapy, remaining inactive until a pathogen is detected, and releasing antibacterial compounds on demand to eliminate the pathogen. This study focuses on the development of genetically engineered probiotics capable of detecting and eradicating P. aeruginosa by producing and secreting PA2-GNU7, a P. aeruginosa-selective antimicrobial peptide (AMP), triggered by the presence of P. aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone (3OC12HSL). To achieve this goal, plasmid-based systems were constructed to produce AMPs in response to 3OC12HSL and secrete them into the extracellular medium using either the microcin V secretion system or YebF as a carrier protein. Following the transfer of these plasmid-based systems to Escherichia coli Nissle 1917 (EcN), we successfully demonstrated the ability of the engineered EcN to express and secrete PA2-GNU7, leading to the inhibition of P. aeruginosa growth in vitro. In addition, in a mouse model of intestinal P. aeruginosa colonization, the administration of engineered EcN resulted in reduced levels of P. aeruginosa in both the feces and the colon. These findings suggest that engineered EcN holds promise as a potential option for combating intestinal P. aeruginosa colonization, thus mitigating the risk of future endogenous infections in vulnerable patients. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Biomedicines)
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17 pages, 4898 KiB  
Article
Novel 5-Nitrofuran-Tagged Imidazo-Fused Azines and Azoles Amenable by the Groebke–Blackburn–Bienaymé Multicomponent Reaction: Activity Profile against ESKAPE Pathogens and Mycobacteria
by Alexander Sapegin, Elizaveta Rogacheva, Lyudmila Kraeva, Maxim Gureev, Marine Dogonadze, Tatiana Vinogradova, Petr Yablonsky, Saeed Balalaie, Sergey V. Baykov and Mikhail Krasavin
Biomedicines 2022, 10(9), 2203; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092203 - 06 Sep 2022
Cited by 2 | Viewed by 1588
Abstract
A chemically diverse set of 13 5-nitrofuran-tagged heterocyclic compounds has been prepared via the Groebke–Blackburn–Bienaymé multicomponent reaction. The testing of these compounds against the so-called ESKAPE panel of pathogens identified an apparent lead compound—N-cyclohexyl-2-(5-nitrofuran-2-yl)imidazo[1,2-a]pyridine-3-amine (4a)—which showed an [...] Read more.
A chemically diverse set of 13 5-nitrofuran-tagged heterocyclic compounds has been prepared via the Groebke–Blackburn–Bienaymé multicomponent reaction. The testing of these compounds against the so-called ESKAPE panel of pathogens identified an apparent lead compound—N-cyclohexyl-2-(5-nitrofuran-2-yl)imidazo[1,2-a]pyridine-3-amine (4a)—which showed an excellent profile against Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis (MIC 0.25, 0.06, 0.25 and 0.25 µg/mL, respectively). Its antibacterial profile and practically convenient synthesis warrant further pre-clinical development. Certain structure-activity relationships were established in the course of this study which were rationalized by the flexible docking experiments in silico. The assessment of antitubercular potential of the compounds synthesized against drug sensitive H37v strain of Mycobacterium tuberculosis revealed little potential of the imidazo-fused products of the Groebke–Blackburn–Bienaymé multicomponent reaction as chemotherapeutic agents against this pathogen. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Biomedicines)
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12 pages, 3401 KiB  
Article
Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
by Casin Le, Camila Pimentel, Fernando Pasteran, Marisel R. Tuttobene, Tomás Subils, Jenny Escalante, Brent Nishimura, Susana Arriaga, Aimee Carranza, Vyanka Mezcord, Alejandro J. Vila, Alejandra Corso, Luis A. Actis, Marcelo E. Tolmasky, Robert A. Bonomo and Maria Soledad Ramírez
Biomedicines 2022, 10(3), 600; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030600 - 03 Mar 2022
Cited by 9 | Viewed by 2585
Abstract
Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human [...] Read more.
Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing Acinetobacter baumannii showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in A. baumannii cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream A. baumannii infections. The exposure of the infecting cells to the host’s fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the A. baumannii susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Biomedicines)
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Review

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38 pages, 4888 KiB  
Review
Microbial Resistance to Antibiotics and Effective Antibiotherapy
by Adriana Aurelia Chiș, Luca Liviu Rus, Claudiu Morgovan, Anca Maria Arseniu, Adina Frum, Andreea Loredana Vonica-Țincu, Felicia Gabriela Gligor, Maria Lucia Mureșan and Carmen Maximiliana Dobrea
Biomedicines 2022, 10(5), 1121; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051121 - 12 May 2022
Cited by 20 | Viewed by 7085
Abstract
Currently, the efficacy of antibiotics is severely affected by the emergence of the antimicrobial resistance phenomenon, leading to increased morbidity and mortality worldwide. Multidrug-resistant pathogens are found not only in hospital settings, but also in the community, and are considered one of the [...] Read more.
Currently, the efficacy of antibiotics is severely affected by the emergence of the antimicrobial resistance phenomenon, leading to increased morbidity and mortality worldwide. Multidrug-resistant pathogens are found not only in hospital settings, but also in the community, and are considered one of the biggest public health concerns. The main mechanisms by which bacteria develop resistance to antibiotics include changes in the drug target, prevention of entering the cell, elimination through efflux pumps or inactivation of drugs. A better understanding and prediction of resistance patterns of a pathogen will lead to a better selection of active antibiotics for the treatment of multidrug-resistant infections. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Biomedicines)
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