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Host-Pathogen Interaction, 6th Edition
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Host-Pathogen Interaction, 6th Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 December 2025) | Viewed by 19068

Special Issue Editor

Prof. Dr. Andreas Burkovski

E-Mail Website
Guest Editor
Microbiology Division, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany
Interests: corynebacteria; host–pathogen interaction; nitrogen control; regulatory networks; secretome analyses; toxins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue, "Host-Pathogen Interaction 5.0".

Microorganisms can interact with larger organisms in many different ways, e.g., beneficially as symbionts, indifferently as commensals, or harmfully as pathogens. Today, a wide variety of molecular and cell biology tools, including advanced microscopy and -omics techniques, allow us to study these interactions at a molecular level. This Special Issue will deal with all aspects of pathogenic microorganisms (e.g., bacteria, yeasts, and protozoa) and their host organisms. Reviews and research articles focusing on either pathogens or hosts are welcome. 

Prof. Dr. Andreas Burkovski
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • microorganisms
  • pathogen
  • bacteria
  • yeasts
  • protozoa
  • host organisms

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Published Papers (7 papers)

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Research

Jump to: Review

21 pages, 4203 KB  
Article
Rv1899c, an HDAC1–ZBTB25-Interacting Protein of Mycobacterium tuberculosis, Promotes Stress Resistance and Immune Evasion in Infected Macrophages
by Arjun M. Menon, Boinapalli Gopichand, Shwetha Susan Thomas, Kuniyil Abhinand, Bipin G. Nair, Geetha B. Kumar, Pradeesh Babu, KB Arun, Lekshmi K. Edison and Aravind Madhavan
Int. J. Mol. Sci. 2025, 26(22), 10872; https://doi.org/10.3390/ijms262210872 - 9 Nov 2025
Viewed by 955
Abstract
Rv1899c, a previously identified HDAC1–ZBTB25-interacting protein of Mycobacterium tuberculosis, plays a crucial role in bacterial adaptation and immune modulation. Recombinant M. smegmatis-expressing Rv1899c (MS_ Rv1899c) showed enhanced survival under acidic and oxidative stress compared to vector controls, along with improved [...] Read more.
Rv1899c, a previously identified HDAC1–ZBTB25-interacting protein of Mycobacterium tuberculosis, plays a crucial role in bacterial adaptation and immune modulation. Recombinant M. smegmatis-expressing Rv1899c (MS_ Rv1899c) showed enhanced survival under acidic and oxidative stress compared to vector controls, along with improved early intracellular growth in THP1-derived macrophages. This was accompanied by reduced reactive oxygen species (ROS), diminished cytokines associated with inflammation and downregulation of autophagy proteins ATG5, Beclin, and LC3, which ultimately skewed the immune response, suppressing the pro-inflammatory M1 macrophage population. Targeting Rv1899c with 3-aminobenzamide (3-AB) impaired intracellular bacterial survival and restored IL-12B expression, while its combination with the HDAC inhibitor C1994 significantly enhanced bacterial clearance. Structural modelling confirmed the high stereochemical quality of the Rv1899c macrodomain, and computational studies identified 3-AB as the strongest ligand (−5.75 kcal/mol), stabilized through hydrogen bonding and hydrophobic interactions with key residues. Molecular dynamics simulations conducted for 200 ns demonstrated stable protein–ligand interactions with consistent parameters, while MM/GBSA analysis indicated favourable binding energy (ΔG_bind = −6.6 kcal/mol), largely influenced by van der Waals and electrostatic forces. Together, these findings highlight Rv1899c as a mediator of stress resistance and immune evasion and propose it as a potential therapeutic target against M. tuberculosis. Full article
(This article belongs to the Special Issue Host-Pathogen Interaction, 6th Edition)
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30 pages, 4989 KB  
Article
Proteomic Analysis of CHIKV-nsP3 Host Interactions in Liver Cells Identifies Novel Interacting Partners
by Nimisha Mishra, Yash Chaudhary, Sakshi Chaudhary, Anjali Singh, Priyanshu Srivastava and Sujatha Sunil
Int. J. Mol. Sci. 2025, 26(14), 6832; https://doi.org/10.3390/ijms26146832 - 16 Jul 2025
Cited by 4 | Viewed by 2365
Abstract
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has re-emerged, causing widespread outbreaks and a significant clinical burden. Despite advances in virology, the molecular mechanisms governing CHIKV’s interaction with host cells remain poorly understood. In this study, we aimed to identify novel host protein interactors [...] Read more.
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has re-emerged, causing widespread outbreaks and a significant clinical burden. Despite advances in virology, the molecular mechanisms governing CHIKV’s interaction with host cells remain poorly understood. In this study, we aimed to identify novel host protein interactors of the CHIKV nonstructural protein 3 (nsP3), a critical component of the viral replication complex, using mass spectrometry-based proteomic profiling in liver-derived Huh7 cells. Co-immunoprecipitation followed by LC-MS/MS identified a wide array of host proteins associated with nsP3, revealing 52 proteins classified as high-confidence (FDR of 1%, and unique peptides > 2) CHIKV-specific interactors. A bioinformatic analysis using STRING and Cytoscape uncovered interaction networks enriched in metabolic processes, RNA processing, translation regulation, cellular detoxification, stress responses, and immune signaling pathways. A subcellular localization analysis showed that many interactors reside in the cytosol, while others localize to the nucleus, nucleolus, and mitochondria. Selected novel host protein interactions were validated through co-immunoprecipitation and immunofluorescence assays. Our findings provide new insights into the host cellular pathways hijacked by CHIKV and highlight potential targets for therapeutic intervention. This is the first report mapping direct nsP3–host protein interactions in Huh7 cells during CHIKV infection. Full article
(This article belongs to the Special Issue Host-Pathogen Interaction, 6th Edition)
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22 pages, 16202 KB  
Article
Multi-Omics Integrative Analysis to Reveal the Impacts of Shewanella algae on the Development and Lifespan of Marine Nematode Litoditis marina
by Yiming Xue, Beining Xue and Liusuo Zhang
Int. J. Mol. Sci. 2024, 25(16), 9111; https://doi.org/10.3390/ijms25169111 - 22 Aug 2024
Cited by 2 | Viewed by 2384
Abstract
Understanding how habitat bacteria affect animal development, reproduction, and aging is essential for deciphering animal biology. Our recent study showed that Shewanella algae impaired Litoditis marina development and lifespan, compared with Escherichia coli OP50 feeding; however, the underlying mechanisms remain unclear. Here, multi-omics [...] Read more.
Understanding how habitat bacteria affect animal development, reproduction, and aging is essential for deciphering animal biology. Our recent study showed that Shewanella algae impaired Litoditis marina development and lifespan, compared with Escherichia coli OP50 feeding; however, the underlying mechanisms remain unclear. Here, multi-omics approaches, including the transcriptome of both L. marina and bacteria, as well as the comparative bacterial metabolome, were utilized to investigate how bacterial food affects animal fitness and physiology. We found that genes related to iron ion binding and oxidoreductase activity pathways, such as agmo-1, cdo-1, haao-1, and tdo-2, were significantly upregulated in L. marina grown on S. algae, while extracellular structural components-related genes were significantly downregulated. Next, we observed that bacterial genes belonging to amino acid metabolism and ubiquinol-8 biosynthesis were repressed, while virulence genes were significantly elevated in S. algae. Furthermore, metabolomic analysis revealed that several toxic metabolites, such as puromycin, were enriched in S. algae, while many nucleotides were significantly enriched in OP50. Moreover, we found that the “two-component system” was enriched in S. algae, whereas “purine metabolism” and “one-carbon pool by folate” were significantly enriched in E. coli OP50. Collectively, our data provide new insights to decipher how diet modulates animal fitness and biology. Full article
(This article belongs to the Special Issue Host-Pathogen Interaction, 6th Edition)
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Review

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14 pages, 2648 KB  
Review
Pathogen-Induced Lysosomal Membrane Permeabilization: A Critical Interface Between Host Defense and Cell Death
by Xiao Liu, Zhan Li, Yuru Hu, Tao Li and Hui Wang
Int. J. Mol. Sci. 2026, 27(3), 1515; https://doi.org/10.3390/ijms27031515 - 3 Feb 2026
Cited by 1 | Viewed by 853
Abstract
During pathogen infection, lysosomes are not only pivotal targets exploited by pathogens to evade host defenses and induce cell death, but also an essential frontline of host protection that restricts infection by degrading invading microbes and repairing membrane damage. A broad spectrum of [...] Read more.
During pathogen infection, lysosomes are not only pivotal targets exploited by pathogens to evade host defenses and induce cell death, but also an essential frontline of host protection that restricts infection by degrading invading microbes and repairing membrane damage. A broad spectrum of pathogens—including bacteria, viruses, protozoa, and fungi—can trigger lysosomal membrane permeabilization (LMP), resulting in the leakage of lysosomal contents into the cytosol. The released lysosomal factors can selectively activate distinct cell-death programs, including apoptosis, pyroptosis, ferroptosis, and necroptosis. These cell-death processes may limit pathogen dissemination by eliminating infected cells, yet they can also exacerbate disease through excessive inflammatory responses and tissue injury. In this review, we highlight recent advances and systematically discuss the determinants of lysosomal membrane stability, methods for detecting LMP, and LMP-driven cell-death modalities, and we summarize the mechanisms and consequences of pathogen-induced LMP. Full article
(This article belongs to the Special Issue Host-Pathogen Interaction, 6th Edition)
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26 pages, 2466 KB  
Review
Cell Surface Shaving-Based Proteomic Profiling of the Surfaceome in Pathogenic Microorganisms
by Dorota Satala, Katarzyna Kowalik and Justyna Karkowska-Kuleta
Int. J. Mol. Sci. 2026, 27(2), 1048; https://doi.org/10.3390/ijms27021048 - 21 Jan 2026
Viewed by 667
Abstract
The microbial cell wall is a dynamic structure responsible for maintaining the shape and integrity of the cell. It is involved in the processes of cell growth, reproduction and division, protection against environmental stress factors, bidirectional selective transport of various molecules, and interactions [...] Read more.
The microbial cell wall is a dynamic structure responsible for maintaining the shape and integrity of the cell. It is involved in the processes of cell growth, reproduction and division, protection against environmental stress factors, bidirectional selective transport of various molecules, and interactions with other microorganisms inhabiting a particular ecological niche. The cell surface of microorganisms pathogenic to humans is also responsible for constant and direct contact with the host during the initiation and further development of the infection, and proteins exposed on the surface play a key role in this phenomenon. The set of proteins exposed on the cell surface is collectively referred to as the surfaceome. In surfaceome studies, the cell surface shaving technique is increasingly used while maintaining cell integrity, which, in addition to providing insight into the composition of surface proteins, also makes it possible to track the interactions of pathogen molecules with host molecules. This experimental approach will be described in this review with examples of the most relevant groups of identified microbial proteins involved in the host–pathogen interactions. Full article
(This article belongs to the Special Issue Host-Pathogen Interaction, 6th Edition)
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29 pages, 1501 KB  
Review
The Role of Heat Shock Protein (Hsp) Chaperones in Environmental Stress Adaptation and Virulence of Plant Pathogenic Bacteria
by Donata Figaj
Int. J. Mol. Sci. 2025, 26(2), 528; https://doi.org/10.3390/ijms26020528 - 9 Jan 2025
Cited by 21 | Viewed by 5284
Abstract
Plant pathogenic bacteria are responsible for a substantial number of plant diseases worldwide, resulting in significant economic losses. Bacteria are exposed to numerous stress factors during their epiphytic life and within the host. Their ability to survive in the host and cause symptomatic [...] Read more.
Plant pathogenic bacteria are responsible for a substantial number of plant diseases worldwide, resulting in significant economic losses. Bacteria are exposed to numerous stress factors during their epiphytic life and within the host. Their ability to survive in the host and cause symptomatic infections depends on their capacity to overcome stressors. Bacteria have evolved a range of defensive and adaptive mechanisms to thrive under varying environmental conditions. One such mechanism involves the induction of chaperone proteins that belong to the heat shock protein (Hsp) family. Together with proteases, these proteins are integral components of the protein quality control system (PQCS), which is essential for maintaining cellular proteostasis. However, knowledge of their action is considerably less extensive than that of human and animal pathogens. This study discusses the modulation of Hsp levels by phytopathogenic bacteria in response to stress conditions, including elevated temperature, oxidative stress, changes in pH or osmolarity of the environment, and variable host conditions during infection. All these factors influence bacterial virulence. Finally, the secretion of GroEL and DnaK proteins outside the bacterial cell is considered a potentially important virulence trait. Full article
(This article belongs to the Special Issue Host-Pathogen Interaction, 6th Edition)
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16 pages, 1063 KB  
Review
Epigenetic Mechanisms Induced by Mycobacterium tuberculosis to Promote Its Survival in the Host
by Shwetha Susan Thomas, Kuniyil Abhinand, Arjun M. Menon, Bipin G. Nair, Geetha B. Kumar, K. B. Arun, Lekshmi K. Edison and Aravind Madhavan
Int. J. Mol. Sci. 2024, 25(21), 11801; https://doi.org/10.3390/ijms252111801 - 2 Nov 2024
Cited by 11 | Viewed by 4952
Abstract
Tuberculosis caused by the obligate intracellular pathogen, Mycobacterium tuberculosis, is one among the prime causes of death worldwide. An urgent remedy against tuberculosis is of paramount importance in the current scenario. However, the complex nature of this appalling disease contributes to the [...] Read more.
Tuberculosis caused by the obligate intracellular pathogen, Mycobacterium tuberculosis, is one among the prime causes of death worldwide. An urgent remedy against tuberculosis is of paramount importance in the current scenario. However, the complex nature of this appalling disease contributes to the limitations of existing medications. The quest for better treatment approaches is driving the research in the field of host epigenomics forward in context with tuberculosis. The interplay between various host epigenetic factors and the pathogen is under investigation. A comprehensive understanding of how Mycobacterium tuberculosis orchestrates such epigenetic factors and favors its survival within the host is in increasing demand. The modifications beneficial to the pathogen are reversible and possess the potential to be better targets for various therapeutic approaches. The mechanisms, including histone modifications, DNA methylation, and miRNA modification, are being explored for their impact on pathogenesis. In this article, we are deciphering the role of mycobacterial epigenetic regulators on various strategies like cytokine expression, macrophage polarization, autophagy, and apoptosis, along with a glimpse of the potential of host-directed therapies. Full article
(This article belongs to the Special Issue Host-Pathogen Interaction, 6th Edition)
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