Genomics: Infectious Disease and Host-Pathogen Interaction

Infectious diseases caused by bacteria, viruses, fungi, and parasites pose serious threats to humans, animals, and plants. Pathogens interact with hosts to inhibit or evade immune responses, and unique genomic features (e.g., mutations, species-specific genes) shape host–pathogen interaction outcomes such as virulence, resistance phenotypes, and disease severity. Advances in next-generation and nanopore sequencing have made genomic, transcriptomic, metagenomic, and small RNA research highly accessible and cost-effective. Host–pathogen interactions are bi-directional, involving both pathogen virulence mechanisms and host defense pathways. Phylogenomics and mutation-based viral detection approaches continue to advance microbiology and diagnostics. This Special Issue compiles twelve original research articles and three reviews spanning biofilm formation, diagnostics, vaccine development, and host–pathogen interactions across genomic, transcriptomic, and microbiomic studies.

The Special Issue includes reviews on: (1) mechanisms and pathogenicity links in Salmonella typhi biofilm formation; (2) mechanisms by which viruses degrade cellular STAT2 to subvert type I interferon signaling; and (3) plant virus exploitation of xylem tissues and interactions with host genes. These reviews synthesize current knowledge and contextualize recent experimental findings on microbial virulence strategies and host defenses.

- Biofilm formation and bacterial virulence: (1) Sub-minimum inhibitory concentrations of imipenem and colistin can induce biofilm-specific antibiotic resistance and virulence genes in Acinetobacter baumannii, increasing biofilm-associated antibiotic tolerance. (2) Recombinant SARS-CoV-2 spike protein and mouse coronavirus inhibit biofilm formation by Streptococcus pneumoniae and Staphylococcus aureus, suggesting potential shifts toward a more virulent planktonic lifestyle relevant to secondary pneumonia in COVID-19. (3) Whole-genome random mutagenesis in Escherichia coli revealed strains with positive association between D-galactose exposure and maltose operon expression had up to 20% lower fitness than wild-type. - Diagnostics and immunization: FTA cards effectively release nucleic acids of African swine fever virus and influenza A virus for downstream diagnostics. A novel vaccination strategy using engineered trypanosomes expressing a PrP-specific peptide elicited strong humoral responses and protected mice against transmissible spongiform encephalopathies. - Viral and host genomics/transcriptomics: (1) Type I interferon induces an antiviral state via STAT2, which many viruses target for degradation. (2) Two Ebola-virus-derived microRNAs were identified in Huh7-infected cells, potentially targeting host genes. (3) Serial passaging of seasonal H3N2 influenza A virus in cell culture generated HA D457G and additional mutations in HA, NA, PB1, PB1-F2, and NS1, indicating adaptive evolution. (4) Porcine circovirus type 4 (PCV4) genomes circulating in China are relatively stable and show higher homology to mink circovirus than to other porcine circoviruses, suggesting potential ancestry or host linkage. - Plant pathogenesis and resources: (1) Plant viruses may colonize xylem; certain host genes in xylem tissues interact with viruses. (2) In Puccinia striiformis f. sp. tritici (wheat stripe rust), 19 SNPs in secreted protein genes were significantly associated with 12 avirulence genes, informing host–pathogen compatibility. (3) A database for alfalfa–Pseudomonas syringae pv. syringae ALF3 interactions provides proteome annotations and orthology-based host–pathogen interactome predictions. - Parasitic protozoa: Transcriptomics of canine DH82 macrophages infected by a less virulent Leishmania infantum strain (BOS1FL1) versus a reference strain (BCN150) showed that phagocytosis and TNF/MAPK/NFκB signaling pathways were altered only with BOS1FL1, suggesting mechanisms underlying reduced virulence. - Microbiomics: Comparative metagenomics (DNA) versus metatranscriptomics (RNA) in overwintering pepper fruits showed DNA sequencing better detects bacteria and DNA viruses, while mRNA sequencing better detects fungi and RNA viruses.

The Special Issue highlights how genomic and transcriptomic technologies elucidate mechanisms of microbial virulence, antibiotic tolerance, and host immune signaling across diverse systems (human, animal, plant). Findings on biofilm modulation, viral miRNAs, and adaptive mutations in influenza underscore dynamic, bidirectional host–pathogen interactions and rapid pathogen evolution. Plant-focused studies and new databases expand resources for dissecting host–pathogen networks and identifying genetic markers linked to virulence/avirulence. Diagnostic advances (FTA cards) and innovative vaccine strategies (engineered trypanosomes) translate molecular insights into practical applications for surveillance and disease prevention. Collectively, these contributions reinforce the importance of integrated multi-omics to inform public health, veterinary medicine, and agriculture.

This editorial synthesizes twelve original studies and three reviews that advance understanding of infectious disease genomics and host–pathogen interactions. Key contributions include insights into biofilm-associated resistance, viral immune evasion and evolution, discovery of viral microRNAs, plant–pathogen molecular interfaces, and practical advances in diagnostics and vaccination. Future work, as implied by these studies, includes leveraging multi-omics to map interaction networks at higher resolution, monitoring pathogen evolution in real time, refining diagnostic sampling and detection workflows, exploring microbiome functional roles, and translating mechanistic findings into vaccines and therapeutics across human, animal, and plant health.