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Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies,...
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Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 22154

Special Issue Editor

Prof. Dr. Alexandra Tabaran

E-Mail Website
Guest Editor
Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Mănăştur Street, No. 3/5, Cluj-Napoca, Romania
Interests: antibiotic; public health; bacteria; mechanism; treatment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue, entitled “Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies”.

Antibiotic and antifungal resistance have become the most important challenges in the field of public health, particularly when treating infections in animals and humans caused by multidrug-resistant strains. The most concerning fact in pathogenic bacterial and fungal growth is their increasing resistance to the various groups of antibiotics that are currently used in therapy. This ongoing process represents the most dangerous threat to the effectiveness of existing antibiotics and antifungal substances, and that is why research is needed to find more effective alternative treatments. There is a need for accurate data concerning the constant way in which bacteria evolve and manage to evade drug influence. In this way, more knowledge will be available to the researchers in the field concerning the mechanisms of resistance and ways to combat it. This Special Issue is focused on publishing multidisciplinary research that focuses on this complex issue. We encourage the publication of all important and updated results in the fields of food microbiology, antibacterial resistance, antifungal resistance, the characterization of alternative methods, efficient antimicrobial and antifungal agents, and development techniques.

Prof. Dr. Alexandra Tabaran
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 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. Microorganisms 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 2700 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

  • antibiotic
  • public health
  • bacteria
  • mechanism
  • treatment

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Published Papers (8 papers)

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Research

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13 pages, 318 KiB  
Article
Real-World Effectiveness and Safety of Isavuconazole Versus Amphotericin B for Patients with Invasive Mucormycosis
by Jiayuan Qin, Hongxia Bi, Guangmin Tang, Xinyao Liu, Junyan Qu, Xiaoju Lv and Yanbin Liu
Microorganisms 2025, 13(1), 55; https://doi.org/10.3390/microorganisms13010055 - 1 Jan 2025
Viewed by 926
Abstract
Background: Invasive mucormycosis (IM) poses a substantial morbidity and mortality burden among immunocompromised patients. Objectives: We aim to compare the real-world effectiveness and safety of isavuconazole with those of amphotericin B in patients with IM. Patients and methods: In this observational cohort study, [...] Read more.
Background: Invasive mucormycosis (IM) poses a substantial morbidity and mortality burden among immunocompromised patients. Objectives: We aim to compare the real-world effectiveness and safety of isavuconazole with those of amphotericin B in patients with IM. Patients and methods: In this observational cohort study, we enrolled patients who were diagnosed with IM and treated with either isavuconazole or amphotericin B. Results: A total of 106 patients met the study criteria. Of these, 47 received isavuconazole, and 59 received amphotericin B as the primary treatment. The two cohorts had similar baseline characteristics, including a history of malignancy, use of immunosuppressants, infection sites, and pathogens. The amphotericin B group demonstrated a significantly greater incidence of renal disorders (p < 0.001) and hypokalemia (p < 0.001) than the isavuconazole group. The proportion of patients who received salvage therapy was greater in the amphotericin B group than in the isavuconazole group (42% vs. 6%, p < 0.001). Eighteen patients in the amphotericin B group discontinued treatment because of adverse events, whereas no patients in the isavuconazole group discontinued treatment because of adverse events. A significant difference in the primary therapeutic response between the isavuconazole and amphotericin B groups was noted (p = 0.013), with a higher treatment failure rate in the amphotericin B group (68% vs. 36%, p = 0.001). However, there were no significant differences in all-cause mortality or mucormycosis-attributable mortality rates between the two groups. Conclusions: Isavuconazole outperformed amphotericin B as a first-line treatment option for IM in terms of its clinical effectiveness and safety. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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12 pages, 6031 KiB  
Article
Outer Membrane Vesicle Production by Escherichia coli Enhances Its Defense against Phage Infection
by Guanhua Xuan, Di Lu, Hong Lin, Yinfeng Wang and Jingxue Wang
Microorganisms 2024, 12(9), 1836; https://doi.org/10.3390/microorganisms12091836 - 5 Sep 2024
Viewed by 1734
Abstract
Several studies have investigated the multifunctional characteristics of outer membrane vesicles (OMVs), but research on their role in mediating phage–bacteria interactions is limited. Employing Escherichia coli as a model, we engineered a mutant strain overproducing OMVs for protective experiments against phage infections. The [...] Read more.
Several studies have investigated the multifunctional characteristics of outer membrane vesicles (OMVs), but research on their role in mediating phage–bacteria interactions is limited. Employing Escherichia coli as a model, we engineered a mutant strain overproducing OMVs for protective experiments against phage infections. The addition of exogenous OMVs proved highly effective in safeguarding the bacterial host against various phages, mitigating predatory threats. Screening for phage-resistant strains and adsorption experiments revealed that inhibiting phage adsorption is a crucial pathway through which OMVs protect against phage predation. Although OMVs conferred tolerance to the phage-sensitive strains (those easily infected by phages), they could not restore the phage-resistant strains (those that effectively resist phage infection) to a sensitive phenotype. This study provides valuable insights for the future development of novel biotechnological approaches aimed at utilizing OMVs to protect fermentative strains and reduce the risk of phage contamination. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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24 pages, 4799 KiB  
Article
Identification, Characterization, and Antibacterial Evaluation of Five Endophytic Fungi from Psychotria poeppigiana Müll. Arg., an Amazon Plant
by Sonia Mendieta-Brito, Mahmoud Sayed, Eunjung Son, Dong-Seon Kim, Marcelo Dávila and Sang-Hyun Pyo
Microorganisms 2024, 12(8), 1590; https://doi.org/10.3390/microorganisms12081590 - 5 Aug 2024
Cited by 1 | Viewed by 1972
Abstract
Endophytic fungi, residing within plants without causing disease, are known for their ability to produce bioactive metabolites with diverse properties such as antibacterial, antioxidant, and antifungal activities, while also influencing plant defense mechanisms. In this study, five novel endophytic fungi species were isolated [...] Read more.
Endophytic fungi, residing within plants without causing disease, are known for their ability to produce bioactive metabolites with diverse properties such as antibacterial, antioxidant, and antifungal activities, while also influencing plant defense mechanisms. In this study, five novel endophytic fungi species were isolated from the leaves of Psychotria poeppigiana Müll. Arg., a plant from the Rubiaceae family, collected in the tropical Amazon region of Bolivia. The endophytic fungi were identified as a Neopestalotiopsis sp., three Penicillium sp., and an Aspergillus sp. through 18S ribosomal RNA sequencing and NCBI-BLAST analysis. Chemical profiling revealed that their extracts obtained by ethyl acetate contained terpenes, flavonoids, and phenolic compounds. In a bioautography study, the terpenes showed high antimicrobial activity against Escherichia coli. Notably, extracts from the three Penicillium species exhibited potent antibacterial activity, with minimum inhibitory concentration (MIC) values ranging from 62.5 to 2000 µg/mL against all three pathogens: Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis (both Gram-positive and Gram-negative bacteria). These findings highlight the potential of these endophytic fungi, especially Penicillium species as valuable sources of secondary metabolites with significant antibacterial activities, suggesting promising applications in medicine, pharmaceuticals, agriculture, and environmental technologies. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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12 pages, 263 KiB  
Article
Virulence and Antimicrobial Resistance of Listeria monocytogenes Isolated from Ready-to-Eat Food Products in Romania
by Mihaela Niculina Duma, Laurenţiu Mihai Ciupescu, Sorin Daniel Dan, Oana Lucia Crisan-Reget and Alexandra Tabaran
Microorganisms 2024, 12(5), 954; https://doi.org/10.3390/microorganisms12050954 - 8 May 2024
Cited by 7 | Viewed by 2316
Abstract
Listeria monocytogenes (L. monocytogenes) poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions. This study investigated the prevalence, serotype distribution, virulence gene profiles, and antimicrobial [...] Read more.
Listeria monocytogenes (L. monocytogenes) poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions. This study investigated the prevalence, serotype distribution, virulence gene profiles, and antimicrobial resistance patterns of L. monocytogenes in ready-to-eat (RTE) food products from Romania. A total of 8151 samples were analyzed, including various processed dairy, bovine, poultry, pork, and fish products. Bacterial isolation was conducted using the classical standard method, followed by confirmation through biochemical and molecular testing. Among the isolated strains, serotypes 1/2a, 1/2b, and 1/2c were identified, with a prevalence of 75% for serotype 1/2a. Additionally, virulence genes specific to listeriolysin O (hlyA) and regulatory factor A (prfA) were detected in all isolates. Antimicrobial susceptibility testing revealed varying resistance patterns among the L. monocytogenes strains. Trimethoprim-sulfamethoxazole and oxacillin showed the highest prevalence of resistance at 26.92% and 23.07%, respectively. However, all strains remained susceptible to ciprofloxacin, levofloxacin, and moxifloxacin. Notably, 23.07% of the isolates exhibited multidrug resistance, with the most common pattern being resistance to oxacillin, penicillin, and tetracycline. Analysis of antimicrobial resistance genes identified tetracycline resistance genes, particularly tet(C), tet(M), and tet(K), in a significant proportion of isolates. The presence of ampC and dfrD genes was also notable, indicating potential mechanisms of resistance. These results emphasize the necessity for ongoing surveillance of L. monocytogenes in RTE foods and emphasize the importance of thorough monitoring of antimicrobial resistance to guide public health strategies within the European Union. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)

Review

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29 pages, 1233 KiB  
Review
Antibiotic-Resistant Pseudomonas aeruginosa: Current Challenges and Emerging Alternative Therapies
by Minqi Hu and Song Lin Chua
Microorganisms 2025, 13(4), 913; https://doi.org/10.3390/microorganisms13040913 - 16 Apr 2025
Viewed by 511
Abstract
Antibiotic-resistant Pseudomonas aeruginosa is a pathogen notorious for its resilience in clinical settings due to biofilm formation, efflux pumps, and the rapid acquisition of resistance genes. With traditional antibiotic therapy rendered ineffective against Pseudomonas aeruginosa infections, we explore alternative therapies that have shown [...] Read more.
Antibiotic-resistant Pseudomonas aeruginosa is a pathogen notorious for its resilience in clinical settings due to biofilm formation, efflux pumps, and the rapid acquisition of resistance genes. With traditional antibiotic therapy rendered ineffective against Pseudomonas aeruginosa infections, we explore alternative therapies that have shown promise, including antimicrobial peptides, nanoparticles and quorum sensing inhibitors. While these approaches offer potential, they each face challenges, such as specificity, stability, and delivery, which require careful consideration and further study. We also delve into emerging alternative strategies, such as bacteriophage therapy and CRISPR-Cas gene editing that could enhance targeted treatment for personalized medicine. As most of them are currently in experimental stages, we highlight the need for clinical trials and additional research to confirm their feasibility. Hence, we offer insights into new therapeutic avenues that could help address the pressing issue of antibiotic-resistant Pseudomonas aeruginosa, with an eye toward practical applications in future healthcare. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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22 pages, 1958 KiB  
Review
Regulation of Ergosterol Biosynthesis in Pathogenic Fungi: Opportunities for Therapeutic Development
by Lingyun Song, Sha Wang, Hang Zou, Xiaokang Yi, Shihan Jia, Rongpeng Li and Jinxing Song
Microorganisms 2025, 13(4), 862; https://doi.org/10.3390/microorganisms13040862 - 10 Apr 2025
Viewed by 465
Abstract
Ergosterol plays a dual role in fungal pathogenesis and azole resistance, driving key advancements in the understanding of its biosynthesis regulation. This review integrates the latest research progress on the regulation of fungal ergosterol biosynthesis and its role in drug resistance and pathogenicity. [...] Read more.
Ergosterol plays a dual role in fungal pathogenesis and azole resistance, driving key advancements in the understanding of its biosynthesis regulation. This review integrates the latest research progress on the regulation of fungal ergosterol biosynthesis and its role in drug resistance and pathogenicity. We comprehensively discuss the functions of key enzymes (such as Erg11p/Cyp51A, Erg6p, Erg3p, and Erg25p) in the mevalonate, late, and alternative pathways. Notably, we highlight the complex regulation of cyp51A expression by factors such as SrbA, AtrR, CBC, HapX, and NCT in Aspergillus fumigatus, and elucidate the distinctive roles of Upc2, Adr1, and Rpn4 in Candida species. Importantly, we summarize recent discoveries on the CprA-dependent regulation of Cyp51A/Erg11p and heme-mediated stability control. Based on these findings, we propose innovative antifungal strategies, including dual-target inhibition and multi-enzyme inhibition by natural products, which provide novel insights and potential directions for the development of next-generation antifungal therapies. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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13 pages, 578 KiB  
Review
Plasmid Dissemination in Multispecies Carbapenemase-Producing Enterobacterales Outbreaks Involving Clinical and Environmental Strains: A Narrative Review
by Louis Alglave, Karine Faure and Catherine Mullié
Microorganisms 2025, 13(4), 810; https://doi.org/10.3390/microorganisms13040810 - 2 Apr 2025
Viewed by 256
Abstract
Outbreaks involving carbapenemase-producing enterobacteria (CPE) have become a common occurrence in healthcare settings. While clonal dissemination is firmly established as a cause for these outbreaks, horizontal gene transfers (HGTs) between different species of Enterobacterales found in clinical and environmental isolates are less so. [...] Read more.
Outbreaks involving carbapenemase-producing enterobacteria (CPE) have become a common occurrence in healthcare settings. While clonal dissemination is firmly established as a cause for these outbreaks, horizontal gene transfers (HGTs) between different species of Enterobacterales found in clinical and environmental isolates are less so. To gather evidence backing up this hypothesis, a review covering the 2013–2024 period was performed. HGTs between different species of clinical and environmental Enterobacterales were identified in thirteen papers, half of those published within the last three years. A combination of short- and long-read whole genome sequencing (WGS) was predominantly used to identify mobile genetic elements and plasmids. The more frequently reported carbapenemases were KPCs, followed by NDMs and IMPs. Predictably, broad-host-range plasmids were responsible for over 50% of HGTs, with the IncA/C group being in the lead. Klebsiella pneumoniae and Enterobacter cloacae complexes were the most frequent species identified in clinical samples, while Citrobacter freundii dominated environmental ones. Drains and pipework frequently constituted CPE reservoirs in protracted outbreaks, alternating epidemic outbursts with silent phases. Including WGS in a systematic environmental surveillance would help in swiftly identifying those CPE reservoirs and possibly help better control plasmid outbursts by allowing the implementation of adequate infection prevention and control measures. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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Other

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57 pages, 609 KiB  
Case Report
Combining Double-Dose and High-Dose Pulsed Dapsone Combination Therapy for Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome and Co-Infections, Including Bartonella: A Report of 3 Cases and a Literature Review
by Richard I. Horowitz, John Fallon and Phyllis R. Freeman
Microorganisms 2024, 12(5), 909; https://doi.org/10.3390/microorganisms12050909 - 30 Apr 2024
Cited by 1 | Viewed by 13168
Abstract
Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients’ cases [...] Read more.
Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients’ cases to illustrate three important variables required for long-term remission. First, diagnosing and treating active co-infections, including Babesia and Bartonella were important. Babesia required rotations of multiple anti-malarial drug combinations and herbal therapies, and Bartonella required one or several 6-day HDDCT pulses to achieve clinical remission. Second, all prior oral, intramuscular (IM), and/or intravenous (IV) antibiotics used for chronic Lyme disease (CLD)/post-treatment Lyme disease syndrome (PTLDS), irrespective of the length of administration, were inferior in efficacy to short-term pulsed biofilm/persister drug combination therapy i.e., dapsone, rifampin, methylene blue, and pyrazinamide, which improved resistant fatigue, pain, headaches, insomnia, and neuropsychiatric symptoms. Lastly, addressing multiple factors on the 16-point multiple systemic infectious disease syndrome (MSIDS) model was important in achieving remission. In conclusion, DDDCT with one or several 6–7-day pulses of HDDCT, while addressing abnormalities on the 16-point MSIDS map, could represent a novel effective clinical and anti-infective strategy in CLD/PTLDS and associated co-infections including Bartonella. Full article
(This article belongs to the Special Issue Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies, Second Edition)
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