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Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria, 2nd...
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Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria, 2nd Edition

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: 30 November 2026 | Viewed by 4473

Special Issue Editor

Dr. Valerie Carabetta

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
Interests: antibiotic resistance; multidrug resistance; lysine acetylation; KAT; KDAC; histone-like proteins; post-translational modifications; mass spectrometry; proteomics; antimicrobial peptides; biofilm
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infections and mortality caused by Gram-negative bacteria (GNBs) are increasing all over the world. Moreover, these types of infections are becoming increasingly difficult to treat, given the concurrent increase in the prevalence of antibiotic-resistant bacteria. Further compounding this problem, GNBs tend to become resistant to multiple drug classes and are referred to as multidrug-resistant (MDR) GNBs, which often leaves physicians with few or no treatment options. In fact, the 2024 World Health Organization priority pathogens list predominantly comprises GNBs, including all those in the critical category. GNBs possess a plethora of resistance strategies, either intrinsic or acquired, to avoid antibiotic-mediated cell death. Resistance genes and determinants rapidly spread among bacterial populations, which contributes to the rapid emergence of MDR strains. Intrinsically, the main weapon of GNBs is their cell wall, specifically the outer membrane, which serves as an excellent permeability barrier to drugs and environmental insults. Bacteria can also acquire or evolve resistance to common skin antiseptics and disinfectants, which contributes to hospital outbreaks of MDR bacteria. Novel strategies to treat and limit the spread of drug-resistant GNBs are imperative and will serve as the primary focus of the second edition of this Special Issue. This research topic focuses on studies (including original research, methods, perspectives, reviews, and commentaries) that explore and discuss the following topics:

  • New insights into the mechanisms of antibiotic or antiseptic resistance;
  • Determination of novel combinations of drugs to eliminate MDR bacteria;
  • Discovery of novel drug targets for antibiotic development;
  • Development of novel in vitro or animal models of infection;
  • Discovery and evaluation of new beta-lacatamase, aminoglycoside-modifying enzyme, or efflux pump inhibitors;
  • Evaluation of the potency of new antibiotics on MDR bacteria;
  • Emergence of new resistance determinants in hospital populations.

Dr. Valerie Carabetta
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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. Antibiotics 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 2900 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

  • gram negative
  • antibiotic resistance
  • antiseptic resistance
  • multidrug resistant
  • extensively drug resistant
  • pandrug resistant
  • MDR
  • XDR
  • PDR
  • efflux pumps
  • mechanisms of resistance
  • beta-lactamase
  • outer membrane

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Related Special Issue

Published Papers (3 papers)

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Research

23 pages, 3315 KB  
Article
Evaluation of Anaerobic Digestion Amended with Micro-Aeration and/or Sound Treatment on the Resistome and Virulence Factor Gene Profiles in Poultry Litter
by Getahun E. Agga and John Loughrin
Antibiotics 2026, 15(2), 153; https://doi.org/10.3390/antibiotics15020153 - 2 Feb 2026
Viewed by 553
Abstract
Background: Commercial broiler farms produce a large amount of litter that must be removed. Anaerobic digestion (AD) is animal manure management technology with the added benefit of producing reusable energy. Our team previously showed that the micro-aeration and sound treatment of animal [...] Read more.
Background: Commercial broiler farms produce a large amount of litter that must be removed. Anaerobic digestion (AD) is animal manure management technology with the added benefit of producing reusable energy. Our team previously showed that the micro-aeration and sound treatment of animal manure during AD increase biogas production. However, their influence on antimicrobial resistance genes (ARGs) and bacterial virulence factor genes (VFGs) is unknown. Therefore, the objective of this study was to evaluate the effect of AD on the resistome and VFGs in poultry litter (PL) and see if the effect is modified by micro-aeration and/or sound treatments. Methods: A field experiment was conducted in four anaerobic digesters that consisted of a control (a standard AD system with no air or sound), micro-aeration, sound, and combined micro-aeration and sound treatments. Overall, 21 samples were collected and analyzed with shotgun metagenomic sequencing. The samples included digestate samples (n = 12) from the four digesters obtained at 6 (baseline, i.e., before beginning of micro-aeration and sound treatments), 23 and 42 weeks, raw PL samples (n = 4), two disks comprised of the same wood as the bedding material, an initial digestate seed sample, and two initial week 0 mix samples. Results: Across all sequence reads (n = 3190) obtained from 21 samples, over 80% of the resistome was composed of four antimicrobial classes: macrolides–lincosamides–streptogramins, tetracyclines, aminoglycosides, and glycopeptides. While the total number of ARGs declined in the control digestor, it increased over time in micro-aerated or sound-treated digesters, and their combination greatly increased the number of ARGs detected. This is a new finding, and it clearly shows that micro-aeration, sound, and their combination treatment during the anaerobic digestion of PL enriches ARGs. In contrast, sound-treated AD by itself significantly (p = 0.035) reduced the mean total ARG abundance compared to the control. The number and abundance of ARGs detected in the initial digestate and PL were lower than those in the AD samples, indicating their enrichment during the AD process. On the other hand, although the AD samples had a lower frequency and abundance of VFGs than the PL, AD did not completely remove the VFGs, and their detection frequency increased over time. While micro-aeration increased the abundance of VFGs compared to the control, this effect was countered by its combination with sound treatment, offering a good animal manure treatment strategy to reduce bacterial VFGs. Conclusions: Although additional research may be required, it was shown that while sound treatment may enrich the occurrence of ARGs, it seems promising to reduce the abundance of ARGs and VFGs during the AD of PL. On the other hand, micro-aeration, alone or when combined with sound treatment, increases the abundance of both ARGs and VFGs. Moreover, the study showed that AD, with or without micro-aeration and sound treatment, is not effective for the complete removal of ARGs and VFGs from poultry litter. Rather, AD systems may act as a hotspot for ARGs, and post-AD treatments such as composting need to be evaluated. Full article
(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria, 2nd Edition)
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11 pages, 775 KB  
Article
Whole Genome Sequencing of Klebsiella variicola Strains Isolated from Patients with Cancer
by Alicja Sękowska, Andrés Carrazco-Montalvo and Yulian Konechnyi
Antibiotics 2025, 14(8), 735; https://doi.org/10.3390/antibiotics14080735 - 22 Jul 2025
Viewed by 1792
Abstract
Background: Klebsiella variicola is a Gram-negative, capsulated, nonmotile, facultative anaerobic rod. It is one of the species belonging to the K. pneumoniae complex. The objective of this study was to gain insights into the antimicrobial resistance and virulence of K. variicola [...] Read more.
Background: Klebsiella variicola is a Gram-negative, capsulated, nonmotile, facultative anaerobic rod. It is one of the species belonging to the K. pneumoniae complex. The objective of this study was to gain insights into the antimicrobial resistance and virulence of K. variicola strains isolated from clinical samples from oncologic patients. Methods: Strain identification was performed using a mass spectrometry method. Whole genome sequencing was conducted for all analyzed strains. Antimicrobial susceptibility was determined using an automated method. The presence of antimicrobial resistance mechanisms and genes encoding extended-spectrum beta-lactamases (ESBL) was assessed using the double-disc synergy test and genotypic methods. Results: All isolates were identified as K. variicola using mass spectrometry and whole genome sequencing (WGS). All isolates were ESBL-positive, and two of them harbored the blaCTX-M-15 gene. In our study, the blaLEN-17 gene was detected in all strains. Genome sequence analysis of the K. variicola isolates revealed the presence of virulence factor genes, including entAB, fepC, ompA, ykgK, and yagWXYZ. Two different plasmids, IncFIB(K) and IncFII, were identified in all of the analyzed K. variicola strains. The detected virulence factors suggest the ability of the bacteria to survive in the environment and infect host cells. All isolates demonstrated in vitro susceptibility to carbapenems. Conclusions: Further studies are needed to confirm whether multidrug-resistant K. variicola strains represent an important pathogen in infections among oncologic patients. Full article
(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria, 2nd Edition)
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11 pages, 370 KB  
Article
Description of Two Resistance-Nodulation-Cell Division Efflux Systems Involved in Acquired Antibiotic Resistance: AxySUV in Achromobacter xylosoxidans and AinCDJ in Achromobacter insuavis
by Arnaud Magallon, Julien Bador, Thomas Garrigos, Caroline Demeule, Anaïs Chapelle, Véronique Varin, Catherine Neuwirth and Lucie Amoureux
Antibiotics 2025, 14(6), 536; https://doi.org/10.3390/antibiotics14060536 - 23 May 2025
Cited by 1 | Viewed by 1585
Abstract
Background/Objectives: Achromobacter xylosoxidans and Achromobacter insuavis are emerging opportunistic pathogens. Several Resistance-Nodulation-cell Division (RND) efflux systems are involved in intrinsic or acquired antibiotic resistance (AxyABM, AxyXY-OprZ, and AxyEF-OprN). The aim of this study was to explore the resistance mechanisms in one-step mutants in [...] Read more.
Background/Objectives: Achromobacter xylosoxidans and Achromobacter insuavis are emerging opportunistic pathogens. Several Resistance-Nodulation-cell Division (RND) efflux systems are involved in intrinsic or acquired antibiotic resistance (AxyABM, AxyXY-OprZ, and AxyEF-OprN). The aim of this study was to explore the resistance mechanisms in one-step mutants in which the efflux systems described to date are not involved: one mutant of A. insuavis AXX-A (AXX-A-Do1) and two mutants of A. xylosoxidans CIP102236 (CIP102236-El9 and CIP102236-Eo4) selected on fluoroquinolones. Methods: In vitro mutants were compared to parental isolates by WGS. RT–qPCR and gene inactivation were used to explore the role of the new efflux systems detected. Results: In the A. insuavis AXX-A mutant (AXX-A-Do1), WGS showed a substitution in the putative regulator of the new RND efflux system AinCDJ. The transporter gene ainD was 79-fold overexpressed in AXX-A-Do1, compared to its parental strain. The inactivation of ainD in AXX-A-Do1 led to a decrease in MICs of ciprofloxacin (8-fold), levofloxacin (8-fold), cefepime (≥8-fold), meropenem (4-fold), doripenem (4-fold), doxycycline (4-fold), minocycline (4-fold), tigecycline (4-fold) and chloramphenicol (≥8-fold). The MICs values obtained were similar to those of the parental strain AXX-A. The same approach allowed the detection of the new efflux system AxySUV in A. xylosoxidans CIP102236 mutants, in which substitutions in the putative AxySUV regulator were associated with the overexpression of the transporter gene axyU. axyU inactivation in the mutants led to a decrease in MICs of ciprofloxacin (8- to 16-fold), levofloxacin (4- to 8-fold), doripenem (4-fold), doxycycline (4-fold), minocycline (4-fold), and chloramphenicol (≥4-fold). Interestingly, axySUV is present in only about 50% of available A. xylosoxidans genomes, whereas ainCDJ is detected in all A. insuavis genomes. Conclusions: This study demonstrated that AinCDJ overproduction is involved in the acquired resistance of A. insuavis to cefepime, meropenem, doripenem, fluoroquinolones, minocycline, doxycycline, tigecycline, and chloramphenicol and that AxySUV overproduction is involved in the acquired resistance of A. xylosoxidans to meropenem, fluoroquinolones, minocycline, doxycycline, and chloramphenicol. Full article
(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria, 2nd Edition)
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