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Pathogens
Special Issues
Bacterial Resistance and Novel Therapeutic Approaches
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Bacterial Resistance and Novel Therapeutic Approaches

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (15 February 2026) | Viewed by 9822

Special Issue Editors

Prof. Dr. Longzhu Cui

E-Mail Website
Guest Editor
Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke-shi 3290498, Japan
Interests: infectious diseases; bacterial drug resistance; Staphylococcus aureus; bacteriophage
Dr. Shinya Watanabe

E-Mail Website
Guest Editor
Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke-shi 3290498, Japan
Interests: antimicrobial resistance; staphylococcal infection; phage therapy
Dr. Hui-min Neoh

E-Mail Website
Guest Editor
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaaan Malaysia, Kuala Lumpur, Malaysia
Interests: antimicrobial resistance; Staphylococcus aureus; pathogen surveillance; infectious diseases

Special Issue Information

Dear Colleagues,

Bacterial resistance is a growing global health threat, making many antibiotics ineffective and leading to prolonged illnesses, higher mortality rates, and increased healthcare costs. Multidrug-resistant pathogens like Staphylococcus aureus and Klebsiella pneumoniae challenge healthcare systems. This Special Issue, “Bacterial Resistance and Novel Therapeutic Approaches,” aims at exploring groundbreaking research in bacterial pathogenesis, resistance mechanisms, and innovative solutions. Topics include, but are not limited to, bacteriophage therapy, antimicrobial peptides, advanced drug delivery systems, and next-generation antibiotics. Furthermore, advancements in diagnostics, biofilm eradication strategies, and immunotherapeutics offer promising avenues to counter resistant infections.

We invite original research articles, reviews, and short communications that contribute to understanding and overcoming bacterial resistance.

Topics of interest include, but are not limited to, the following:

  • Mechanisms of bacterial resistance to existing antimicrobials;
  • Innovations in phage-based therapies and bacteriophage engineering;
  • Development of novel antimicrobial agents and drug repurposing strategies;
  • Advances in diagnostic tools for resistant bacterial infections;
  • Biofilm-related infections and methods for biofilm disruption;
  • Host–pathogen interactions and immunomodulatory therapies;
  • Strategies to prevent the spread of resistant pathogens in healthcare settings;
  • Applications of artificial intelligence and omics technologies in combating bacterial resistance.

Prof. Dr. Longzhu Cui
Dr. Shinya Watanabe
Dr. Hui-min Neoh
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 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. Pathogens 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 2200 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
  • bacteriophage therapy
  • novel antimicrobials
  • drug-resistant bacteria
  • biofilm disruption
  • innovative therapeutics
  • host–pathogen interaction

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

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Research

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20 pages, 2038 KB  
Article
In Vitro Evaluation of Colistin–Meropenem Activity Against XDR and PDR Carbapenemase-Producing Klebsiella pneumoniae and Acinetobacter baumannii
by Shahinda Rezk, Nada Younis Elwakeel, Abeer Ghazal, Amel Elsheredy, Daniel Baecker and Ahmed Noby Amer
Pathogens 2026, 15(2), 214; https://doi.org/10.3390/pathogens15020214 - 13 Feb 2026
Viewed by 598
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Acinetobacter baumannii (CRAB) pose significant therapeutic challenges due to their high resistance and global spread. Combination therapy with colistin (COL) and meropenem (MEM) was used to enhance antimicrobial activity. This study evaluated the COL-MEM combination against CRKP and [...] Read more.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Acinetobacter baumannii (CRAB) pose significant therapeutic challenges due to their high resistance and global spread. Combination therapy with colistin (COL) and meropenem (MEM) was used to enhance antimicrobial activity. This study evaluated the COL-MEM combination against CRKP and CRAB isolates with a high resistance profile. A total of 58 carbapenem-resistant clinical isolates (31 CRKP and 27 CRAB), including extensively resistant and pandrug-resistant strains, were collected over a period of 12 months. Synergy between COL and MEM was assessed by microdilution checkerboard (MCB) and time-kill (TKA) assays. Carbapenemase genes were detected using molecular methods. The results showed that the COL-MEM combination yielded synergy (35.5% and 40.7%, respectively) and additive effects (35.5% and 37.0%, respectively), while no antagonism was observed. TKA confirmed bactericidal activity, especially at doubled MCB-detected concentrations, indicating dose-dependent activity. The significant reduction in the minimum inhibitory concentration in the combination indicated its potential for dose optimization, minimizing COL-associated toxicities. Genotypic profiling showed that the expression of blaNDM and blaOxa-48 can reduce synergy. These findings, obtained with isolates of high resistance, support the efficacy of this combination therapy and could reduce the dose-related side effects of COL. However, they also highlight genotype-specific variations and COL resistance mechanisms as limiting variables. Full article
(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)
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16 pages, 1178 KB  
Article
Characterisation of a Novel Pseudomonas Phage and Its Effect on the Survival of Galleria mellonella Larvae
by Sukran Ozturk, Hilal Basak Erol, Banu Kaskatepe and Wan-Ting Huang
Pathogens 2025, 14(12), 1248; https://doi.org/10.3390/pathogens14121248 - 6 Dec 2025
Viewed by 727
Abstract
Multi-drug-resistant Pseudomonas aeruginosa (P. aeruginosa) commonly causes infections that are difficult to treat, necessitating the development of new therapeutics. The search for more effective ways to combat the emergence of bacterial resistance has also led to research into phage-antibiotic synergy (PAS) [...] Read more.
Multi-drug-resistant Pseudomonas aeruginosa (P. aeruginosa) commonly causes infections that are difficult to treat, necessitating the development of new therapeutics. The search for more effective ways to combat the emergence of bacterial resistance has also led to research into phage-antibiotic synergy (PAS) as a potential therapeutic strategy. The aim of this study was to isolate and characterize virulent phages from water sources that are active against clinical carbapenem-resistant P. aeruginosa isolates, and to evaluate their in vivo efficacy using a Galleria mellonella larvae infection model. The biological and genomic characteristics of the isolated phages were determined using host range analysis, one-step growth curve analysis, transmission electron microscopy analysis and whole-genome sequencing. Two phages (vB_PaMB13 and vB_PaMB17) that demonstrated in vitro synergistic and bactericidal interactions with antipseudomonal antibiotics (tobramycin and ceftazidime) were selected for further investigation using the checkerboard method. The study revealed synergy between all phages and either antibiotic, tobramycin or ceftazidime, against P. aeruginosa. Similarly, the percentage survival rates increased in the in vivo model when both phages and antibiotics were used in combination. Overall, our study provides further support for the idea that phage-antibiotic synergy could be an effective strategy for improving treatment outcomes. Full article
(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)
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25 pages, 1368 KB  
Article
Mutational Analysis of Colistin-Resistant Pseudomonas aeruginosa Isolates: From Genomic Background to Antibiotic Resistance
by Telma De Sousa, Hsin-Yao Wang, Ting-Wei Lin, Manuela Caniça, Miguel J. N. Ramos, Daniela Santos, Catarina Silva, Sónia Saraiva, Racha Beyrouthy, Richard Bonnet, Michel Hébraud, Gilberto Igrejas and Patrícia Poeta
Pathogens 2025, 14(4), 387; https://doi.org/10.3390/pathogens14040387 - 15 Apr 2025
Cited by 3 | Viewed by 2415
Abstract
This study analyzed eleven isolates of colistin-resistant Pseudomonas aeruginosa, originating from Portugal and Taiwan, which are associated with various pathologies. The results revealed significant genetic diversity among the isolates, with each exhibiting a distinct genetic profile. A prevalence of sequence type ST235 [...] Read more.
This study analyzed eleven isolates of colistin-resistant Pseudomonas aeruginosa, originating from Portugal and Taiwan, which are associated with various pathologies. The results revealed significant genetic diversity among the isolates, with each exhibiting a distinct genetic profile. A prevalence of sequence type ST235 was observed, characterizing it as a high-risk clone, and serotyping indicated a predominance of type O11, associated with chronic respiratory infections in cystic fibrosis (CF) patients. The phylogenetic analysis demonstrated genetic diversity among the isolates, with distinct clades and complex evolutionary relationships. Additionally, transposable elements such as Tn3 and IS6 were identified in all isolates, highlighting their importance in the mobility of antibiotic resistance genes. An analysis of antimicrobial resistance profiles revealed pan-drug resistance in all isolates, with a high prevalence of genes conferring resistance to β-lactams and aminoglycosides. Furthermore, additional analyses revealed mutations in regulatory networks and specific loci previously implicated in colistin resistance, such as pmrA, cprS, phoO, and others, suggesting a possible contribution to the observed resistant phenotype. This study has a strong impact because it not only reveals the genetic diversity and resistance mechanisms in P. aeruginosa but also identifies mutations in regulatory genes associated with colistin resistance. Full article
(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)
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Review

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17 pages, 1027 KB  
Review
Chimeric Antigen Receptor Immunotherapy for Infectious Diseases: Current Advances and Future Perspectives
by Maria Kourti, Paschalis Evangelidis, Emmanuel Roilides and Elias Iosifidis
Pathogens 2025, 14(8), 774; https://doi.org/10.3390/pathogens14080774 - 5 Aug 2025
Cited by 5 | Viewed by 2625
Abstract
Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and [...] Read more.
Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article
(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)
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Other

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15 pages, 530 KB  
Systematic Review
Resistance of Acinetobacter baumannii Complex Clinical Isolates to Sulbactam–Durlobactam: A Systematic Review of Data from In Vitro Studies
by Matthew E. Falagas, Laura T. Romanos, Dimitrios Ragias and Charalampos Filippou
Pathogens 2025, 14(10), 1062; https://doi.org/10.3390/pathogens14101062 - 20 Oct 2025
Viewed by 2704
Abstract
Introduction: Due to the limited therapeutic options for patients with Acinetobacter baumannii complex infections, a new combination antimicrobial agent, sulbactam–durlobactam, has been developed. In this systematic review, we evaluated the available data on the resistance of A. baumannii complex clinical isolates to sulbactam–durlobactam. [...] Read more.
Introduction: Due to the limited therapeutic options for patients with Acinetobacter baumannii complex infections, a new combination antimicrobial agent, sulbactam–durlobactam, has been developed. In this systematic review, we evaluated the available data on the resistance of A. baumannii complex clinical isolates to sulbactam–durlobactam. Methods: We performed a thorough search of four databases for relevant studies. The Clinical and Laboratory Standards Institute (CLSI) sulbactam–durlobactam breakpoint for A. baumannii complex susceptibility was used (MIC value ≤4 mg/L). Data on the presence of genes of various β-lactamases were also analyzed. Results: From 182 identified articles, 84 were thoroughly screened. Data extraction was performed on 20 articles (published 2017–2025) reporting on a total of 10,412 A. baumannii complex clinical isolates. Among the various β-lactamases genes present, the OXA subvariants OXA-23/OXA-23-like were the most common (in 561 isolates). The proportions of non-selected (consecutive) A. baumannii isolates found to be resistant to sulbactam–durlobactam were 1.2%, 1.2%, and 4.6% in the three studies, and with non-susceptibility (resistance and intermediate resistance) were 2%, 2.1%, and 4.6% in three other studies. Non-susceptibility was very rare among A. calcoaceticus, A. nosocomialis, and A. pittii isolates (0%, 0.3%, and 0.6%, respectively). The proportion of carbapenem-resistant A. baumannii isolates with resistance was 0–5.2%. The proportion of A. baumannii isolates selected for their reduced susceptibility profile (including reduced susceptibility to cefiderocol) with resistance was 1.4–27.3%. Discussion: The low proportion of sulbactam–durlobactam resistance among A. baumannii complex isolates supports the consideration of the use of this new antibiotic for its approved indications. Full article
(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)
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