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Biomedicines
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Mechanisms, Implications, and Therapeutic Targets in Infectious Diseases
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Mechanisms, Implications, and Therapeutic Targets in Infectious Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 5696

Special Issue Editors

Dr. Mihai Lazăr

E-Mail Website
Guest Editor
Clinical Department 2, Division of Physiopathology II, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, RO-020021 Bucharest, Romania
Interests: Infectious diseases; pathophysiology; endocrinology & metabolism; developmental biology.
Dr. Oana Săndulescu

E-Mail Website
Guest Editor
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, No. 1 Dr. Calistrat Grozovici Street, 021105 Bucharest, Romania
Interests: infectious diseases; HIV; viral hepatitis; biofilm; influenza; vaccine-preventable diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infectious diseases remain a significant global health challenge, exerting immense socioeconomic burdens and posing threats to public health infrastructures. Effective strategies for preventing, monitoring, and controlling infectious diseases can be developed by examining their epidemiology, transmission dynamics, and associated risk factors. Pathogens employ various strategies to evade host defenses and establish infection, including immune evasion, antigenic variation, and the manipulation of host cellular processes. Identifying therapeutic targets within the complex network of host–pathogen interactions may lead to the development of new treatments and interventions, such as antimicrobial drugs, immunotherapies, and vaccines. A multidisciplinary approach is necessary in understanding how pathogens invade, replicate, and interact with host cells, tissues, and immune responses. This is crucial for unraveling the complexities of infectious diseases, ranging from common infections to novel microorganisms.

Furthermore, the emergence of antimicrobial resistance poses a formidable challenge, rendering conventional treatments ineffective and exacerbating the burden of infectious diseases. Addressing these implications necessitates a multifaceted approach, encompassing surveillance, prevention, and treatment strategies tailored to specific pathogens and contexts.

This Special Issue welcomes high-quality original research and review articles concerning viral, bacterial, and fungal infections, contributing to a better understanding, diagnosis, and therapeutic management of infectious diseases.

Dr. Mihai Lazăr
Dr. Oana Săndulescu
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

  • infectious diseases
  • virus
  • antibiotics
  • pathophysiology
  • molecular mechanism
  • therapeutic management

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Published Papers (5 papers)

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Research

Jump to: Review

18 pages, 958 KiB  
Article
Evaluation of the Diagnosis and Antibiotic Therapy of Sepsis in the Emergency Department: A Retrospective Observational Study
by Eszter Varga, Sándor Somodi, Máté Molnár, Dóra Ujvárosy, Krisztina Gaál, Attila Vaskó, Zoltán Szabó, Ildikó Bácskay, István Lekli and Adina Fésüs
Biomedicines 2025, 13(7), 1566; https://doi.org/10.3390/biomedicines13071566 - 26 Jun 2025
Viewed by 323
Abstract
Background/Objectives: Sepsis is one of the most common causes of death worldwide, and its diagnosis remains a challenge for clinicians. The main purpose of this study was to appraise the diagnosis and antibiotic prescription pattern for sepsis admitted to the Emergency Department [...] Read more.
Background/Objectives: Sepsis is one of the most common causes of death worldwide, and its diagnosis remains a challenge for clinicians. The main purpose of this study was to appraise the diagnosis and antibiotic prescription pattern for sepsis admitted to the Emergency Department (ED), comparing Sepsis-2 to Sepsis-3 criteria. Methods: The study was conducted in an ED of a tertiary care medical center in Hungary. We included all adult patients who were diagnosed with sepsis in 2023. Data collection was made manually from UD MED System. Diagnosis was assessed based on Sepsis-2 and Sepsis-3 criteria, then compared. Further analyses were made only in cases with confirmed sepsis diagnosis. Antibiotic guideline adherence was determined according to the local guideline in force. Fisher’s exact test, t-test, and ANOVA were applied to compare categorical and continuous variables between groups. The Kaplan–Meier test was applied for probability of survival. Significant p-values were defined as below 0.05. Results: The substantial majority of patients recorded with sepsis in the ED met both the Sepsis-2 and Sepsis-3 criteria (80%), while the rate of misdiagnosis was similar (Sepsis-2: 16/91, 17.6% and Sepsis-3: 14/91, 15.4%). The most important identified risk factors in sepsis were old age (60+ years) and comorbidities (CCI ≥ 4). Elevated LDH (median 325 mg/dL) and decreased albumin levels (median 26 g/L) can be used as early indicators of sepsis. Although the time to first antibiotic administration was not associated with significantly better clinical outcomes, the guideline-adherent agent selection (Sepsis-2: 18/43, 41.9% and Sepsis-3: 19/46: 41.3%) led to a significantly longer survival (median 37 vs. 4 days). Conclusions: No significant differences were found in diagnostic accuracy or prediction of mortality between Sepsis-2 and Sepsis-3. Guideline-adherent antibiotics may lead to significantly higher survival rate in sepsis. Full article
(This article belongs to the Special Issue Mechanisms, Implications, and Therapeutic Targets in Infectious Diseases)
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29 pages, 5219 KiB  
Article
Design and Validation of a Multi-Epitope mRNA Vaccine Construct Against Human Monkeypox Virus (hMPXV) by Annotating Protein of Intracellular Mature Virus (IMV) Form of hMPXV
by Mohammad Asrar Izhari, Siraj B. Alharthi, Raed A. Alharbi, Ahmad H. A. Almontasheri, Wael A. Alghamdi, Abdulmajeed Abdulghani A. Sindi, Ahmad Abdulmajed Salem, Ali Mahzari, Fahad Alghamdi and Ahmed R. A. Gosady
Biomedicines 2025, 13(6), 1439; https://doi.org/10.3390/biomedicines13061439 - 11 Jun 2025
Viewed by 773
Abstract
Background: hMPXV poses a major public health risk due to its human-to-human transmissibility, severe complications, especially in immunocompromised individuals, and global spread, necessitating effective surveillance and stringent prophylactic measures to mitigate its colossal impact. Objective: The study aimed to annotate hMPXV(IMV) [...] Read more.
Background: hMPXV poses a major public health risk due to its human-to-human transmissibility, severe complications, especially in immunocompromised individuals, and global spread, necessitating effective surveillance and stringent prophylactic measures to mitigate its colossal impact. Objective: The study aimed to annotate hMPXV(IMV) proteins to propose a potential reverse vaccinology-based vaccine against hMPXV. Methods: The target MPXV(IMV) protein’s sequences, formatted in FASTA, were sourced from genome/proteome databases (BV-BRC and UniProt) (accessed on 6 November 2024), followed by CD-Hit-based redundancy removal. Epitope prediction for B-cells (lymphocytes), cytotoxic T-cells or cytotoxic T-lymphocytes (CTLs), and helper T-cells (HTLs) was executed using ABCpred, IEDB’s ANNs 4.0, and an artificial neural network-based alignment tool (NN-align 2.3)/ML-based tool (NetMHCII 2.3). Various immunoinformatics filters (antigenicity, toxicity, and allergenicity) were applied to substantiate the potency and safety of the formulated vaccine candidate. The constructed vaccine’s physiochemical and structural features (secondary and tertiary), with structural stability (confirmed by molecular docking followed by dynamic simulation with TLRs (TLR4 & TLR2) and MHCs), were determined. Additionally, cloning (using pET-28a(+) vector) was conducted to verify the vaccine’s expression potential and translation efficiency. The construct’s population coverage was also ascertained. Results: The MPXV-2-Beta vaccine constructs, of the six initially designed constructs, was identified as the most promising candidate, signifying nonallergenic profile and nontoxic features, with a predicted antigenicity score (PAS) = 0.7202, 407 residues, a molecular weight of 43,102.1 Da, pI of 9.2, and favorable stability parameters (AI: 65.65, GRAVY: −0.597, I-i: 25.92). It showed high solubility (score: 0.942). The ProSA Z-score of −9.38 confirmed the structural stability, reliability, and precision of the MPXV-2-Beta 3D model, which is comparable to experimental structures. Furthermore, 98.8% of all the residues nested within favored or allowed regions in a critical Ramachandran plot signified the model’s exceptional structural integrity and quality. Docking and dynamic simulation of MPXV-2-Beta with TLRs (TLR4 & TLR2) and MHCs demonstrated stiffer docking stability (strong polar and nonpolar interaction) and negative eigenvalue value (during dynamic simulation), suggesting its ability to enhance immune receptor activation under physiological conditions. MPXV-2-Beta was predicted to trigger a robust immune response (IR) with comprehensive world population coverage (98.55%, SD = 10.41). Conclusions: Based on the evaluated parameters, the MPXV-2-Beta designed in this study exhibited significant potential as an effective candidate against hMPXV. This study establishes a foundation for developing an efficient vaccine against hMPXV, requiring further experimental and clinical validation to confirm computational findings. Full article
(This article belongs to the Special Issue Mechanisms, Implications, and Therapeutic Targets in Infectious Diseases)
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13 pages, 2364 KiB  
Article
Bacterial Diversity in Native Heart Valves in Infective Endocarditis
by Anna Sinitskaya, Alexander Kostyunin, Maxim Asanov, Maria Khutornaya, Anastasia Klyueva, Alyona Poddubnyak, Alexey Tupikin, Marsel Kabilov and Maxim Sinitsky
Biomedicines 2025, 13(1), 245; https://doi.org/10.3390/biomedicines13010245 - 20 Jan 2025
Viewed by 1659
Abstract
Background: Infective endocarditis (IE) is an infectious disease caused by the hematogenous dissemination of bacteria into heart valves. Improving the identification of pathogens that cause IE is important to increase the effectiveness of its therapy and reduce the mortality caused by this pathology. [...] Read more.
Background: Infective endocarditis (IE) is an infectious disease caused by the hematogenous dissemination of bacteria into heart valves. Improving the identification of pathogens that cause IE is important to increase the effectiveness of its therapy and reduce the mortality caused by this pathology. Methods: Ten native heart valves obtained from IE patients undergoing heart valve replacements were analyzed. Bacterial invasion in the heart valves was studied by Gram staining of histological sections. Histopathological changes accompanied with bacterial invasion were studied by immunohistochemical analysis of pan-leukocyte marker CD45, platelet marker CD41, and neutrophil myeloperoxidase. The taxonomic diversity of the bacteria was analyzed using 16S rRNA metabarcoding. Results: Gram staining of the histological sections revealed bacterial cells localized on the atrial surface at the leaflet’s free edge or on the ventricular surface at the leaflet’s base within fibrin deposits in only three of the studied heart valves. Bacterial colonies were co-localized with microthrombi (CD41+ cells) containing single leucocytes (CD45+ cells), represented by segmented neutrophils. As a result of 16S rRNA metabarcoding, we detected the following bacterial genera: Pseudomonas (70% of the studied heart valves), Roseateles (60%), Acinetobacter (40%), Sphingomonas (40%), Enterococcus (30%), Reyranella (20%), Sphingobium (20%), Streptococcus (20%), Agrobacterium (20%), Ralstonia (10%), and Bacillus (10%). Conclusions: A number of opportunistic microorganisms that could not be detected by routine laboratory tests and were not eliminated during antibiotic therapy were identified in the IE-affected heart valves. The obtained results show the importance of 16S rRNA metabarcoding of heart valves removed due to IE not only as an independent diagnostic method but also as a highly accurate approach that complements routine tests for pathogen identification. Full article
(This article belongs to the Special Issue Mechanisms, Implications, and Therapeutic Targets in Infectious Diseases)
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Review

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17 pages, 401 KiB  
Review
The Therapeutic Potential of Insulin Eye Drops in Neurotrophic Keratopathy: A Comprehensive Review
by Roxana Scripcă, Sinziana Istrate, Emil Ungureanu, Ștefan Oprea, Nicoleta Anton, Madalina Boruga, Marius Alexandru Moga and Ancuța-Georgiana Onofrei
Biomedicines 2025, 13(7), 1657; https://doi.org/10.3390/biomedicines13071657 - 7 Jul 2025
Viewed by 625
Abstract
This review explores the potential role of topical insulin drops in corneal regeneration by analyzing the mechanism of action and clinical outcomes. Corneal integrity restoration is crucial for ocular surface healing. This review synthesizes the current literature on topical insulin for neurotrophic keratopathy [...] Read more.
This review explores the potential role of topical insulin drops in corneal regeneration by analyzing the mechanism of action and clinical outcomes. Corneal integrity restoration is crucial for ocular surface healing. This review synthesizes the current literature on topical insulin for neurotrophic keratopathy (NK), highlighting its mechanism of action, therapeutic potential, and clinical outcomes. Recent studies report high rates of epithelial regeneration, suggesting that topical insulin may be an effective adjunct or alternative to conventional treatments. Further randomized controlled trials are needed to confirm its long-term efficacy and optimal dosing. Methods: Considering the limited regenerative capacity of the corneal epithelium in NK and the increasing interest in novel therapy, we review the existing literature to evaluate the role and extent of topical insulin’s contribution to corneal healing by applying the PICO framework, which allows for a clear and systematic approach to literature selection and evaluation. The literature search and study selection were conducted manually following PRISMA guidelines. Conclusions: Most of the studies resulting from the selection have small samples, and there is a lack of large, randomized clinical trials. The evidence reviewed in this study suggests that topical insulin is a promising therapy for promoting corneal healing in neurotrophic keratopathy. While clinical trials have demonstrated significant epithelial regeneration, optimal dosing and long-term safety require further investigation. Compared to conventional treatments such as autologous serum or growth factor therapy, insulin eye drops provide a cost-effective alternative. Additional research through controlled trials is needed to formulate standardized therapeutic protocols and verify long-term outcomes. Full article
(This article belongs to the Special Issue Mechanisms, Implications, and Therapeutic Targets in Infectious Diseases)
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23 pages, 410 KiB  
Review
Passive Immunisation in the Treatment of Infectious Diseases Related to Highly Potent Bacterial Toxins
by Marta Prygiel, Ewa Mosiej, Karol Wdowiak and Aleksandra Anna Zasada
Biomedicines 2024, 12(12), 2920; https://doi.org/10.3390/biomedicines12122920 - 23 Dec 2024
Cited by 2 | Viewed by 1618
Abstract
The discovery of microbial toxins as the primary factors responsible for disease manifestations and the discovery that these toxins could be neutralised by antitoxins are linked to the birth of immunology. In the late 19th century, the serum or plasma of animals or [...] Read more.
The discovery of microbial toxins as the primary factors responsible for disease manifestations and the discovery that these toxins could be neutralised by antitoxins are linked to the birth of immunology. In the late 19th century, the serum or plasma of animals or patients who had recovered from infectious diseases or who had been immunised with a relevant antigen began to be used to treat or prevent infections. Before the advent of widespread vaccination campaigns, antitoxins played a key role in the treatment and prevention of diseases such as diphtheria and tetanus. A significant reduction in mortality following the introduction of antitoxins confirmed their efficacy. Serum therapy remains an important measure for post-exposure prophylaxis and for the treatment of unvaccinated or incompletely vaccinated patients. For the botulinum toxin, antitoxin therapy continues to be the sole available treatment. The manuscript contains a summary of the most important information on the passive immunoprophylaxis used in the treatment of diphtheria, tetanus, and botulism, all representing diseases in which symptoms are driven by the activity of highly potent bacterial toxins. Full article
(This article belongs to the Special Issue Mechanisms, Implications, and Therapeutic Targets in Infectious Diseases)
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