Extremophilic bacteria survive salt, temperature, and pH extremes by coordinating stress-induced protein networks that preserve macromolecules, sustain energetics, and repair damage. This review integrates recent proteomics with functional genomics to resolve both network state and causality across halophiles, thermophiles, acidophiles, and alkaliphiles, with targeted contrasts from psychrophiles and radiation-resistant bacteria. Quantitative proteomics maps condition-specific induction of chaperones, proteases, ion transporters, osmolyte pathways, DNA repair proteins, antioxidants, and envelope remodelling enzymes. Complementary perturbation genetics/functional genomics and transcriptomics help identify essential nodes and regulatory circuits underlying stress tolerance. In halophiles, compatible solute synthesis and Na+/H+ exchange couple to protein quality control and central metabolism. Thermophiles rely on heat-shock systems, ATP-dependent proteolysis, membrane adjustments, and redox balancing. Acidophiles maintain near-neutral cytosol via proton export and low-permeability membranes while linking iron handling to oxidative defence. Alkaliphiles use Na+-based bioenergetics, multi-subunit antiporters, and cell wall modifications to retain protons. Psychrophiles emphasize cold-shock RNA chaperones, flexible enzymes, and cryoprotectants, whereas radiophiles combine exceptional DNA repair with strong antioxidant capacity. Across clades, oxidative stress forms a cross-cutting axis that explains extensive regulon overlap and cross-protection. We synthesize network architecture, highlight conserved modules and lineage-specific solutions, and outline open questions in stress sensing, multi-stress integration, and functions of uncharacterized proteins. These insights provide a framework for engineering robust biocatalysts and organisms for biotechnology and environmental applications.

The infant gut microbiota significantly influences health outcomes, impacting digestion, immunity, and metabolic processes. Identifying beneficial microbes from this source offers promising avenues for novel probiotic development. This study aimed to identify and characterize potential probiotic bacterial isolates from infant fecal samples using 16S rRNA–based identification and in vitro experimental evaluations. A total of 47 isolates were initially screened. Two promising candidates, Lb. paracasei IF5YR and Ent. faecium IF5RW2, were selected and evaluated for gastrointestinal resilience (acid and bile tolerance), functional properties (autoaggregation, cell surface hydrophobicity, bile salt hydrolase activity, antioxidant activity via FRAP, ABTS, and DPPH assays), and safety (antibiotic susceptibility). Their genetic affiliations were confirmed using 16S rRNA sequencing, followed by bioinformatics and phylogenetic analyses. Both Lb. paracasei IF5YR and Ent. faecium IF5RW2 demonstrated strong acid (pH 1.5) and bile (2%) tolerance, high autoaggregation (>70%), and notable cell surface hydrophobicity (>90% for xylene). Comparative analysis of antibiotic susceptibility confirmed their safety. Phylogenetic analysis based on 16S rRNA sequencing supported the taxonomic affiliation of the isolates. Functionally, both strains exhibited bile salt hydrolase activity and strong antioxidant potential, with FRAP values exceeding 75%. These findings suggest Lb. paracasei IF5YR and Ent. faecium IF5RW2 may be considered potential candidates for probiotic applications related to gut health and oxidative stress modulation. They hold potential for development as novel functional food ingredients or health-promoting supplements, although in vivo or clinical studies are needed to confirm any therapeutic effects.

Extremophilic prokaryotes survive salt, temperature, and pH extremes by coordinating stress-induced protein networks that preserve macromolecules, sustain energetics, and repair damage. This review integrates recent proteomics with functional genomics to resolve both network state and causality across halophiles, thermophiles, acidophiles, alkaliphiles, psychrophiles, and radiation-resistant prokaryotes. Quantitative proteomics maps condition-specific induction of chaperones, proteases, ion transporters, osmolyte pathways, DNA repair proteins, antioxidants, and envelope remodeling enzymes. Complementary perturbation genetics, functional genomics, and transcriptomics help to identify essential nodes and regulatory circuits underlying stress tolerance. In halophiles, compatible solute synthesis and Na⁺/H⁺ exchange couple to protein quality control and central metabolism, whereas many archaeal halophiles additionally rely on high intracellular salt and distinctive membrane chemistry. Thermophiles rely on heat-shock systems, ATP-dependent proteolysis, membrane adjustments, and redox balancing. Acidophiles maintain near-neutral cytosol via proton export and low-permeability membranes while linking iron handling to oxidative defense. Alkaliphiles use Na⁺-based bioenergetics, multi-subunit antiporters, and cell-wall modifications to retain protons. Psychrophiles emphasize cold-shock RNA chaperones, flexible enzymes, and cryoprotectants, whereas radiophiles combine exceptional DNA repair with strong antioxidant capacity. Across taxa, oxidative stress forms a cross-cutting axis that explains extensive regulon overlap and cross-protection. We synthesize network architecture, highlight conserved modules and lineage-specific solutions, and outline open questions in stress sensing, multi-stress integration, and the functions of uncharacterized proteins. These insights provide a framework for engineering robust biocatalysts and organisms for biotechnology and environmental applications.

Environmental microbiomes - especially diverse soil and terrestrial communities - harbor an immense and largely untapped reservoir of microbial genetic diversity. Integrating metagenomic sequencing of these habitats with immunoinformatics offers a new avenue to discover candidate antigens and microbial metabolites that modulate immunity. Metagenomics characterizes the mixed microbial genomes present in soil, water, or microplastic-associated biofilms, enabling recovery of genes and proteins (often via assembly and binning into metagenome-assembled genomes). Immunoinformatics tools can then predict B- and T-cell epitopes or antigenicity of these metagenome-derived proteins, prioritizing those likely to engage host immune receptors. Pipelines such as reverse vaccinology frameworks (e.g., ReVac, VaxiJen, Vaxign) screen genomes using features like surface localization, epitope content, and conservation. New Artificial Intelligence/Machine Learning approaches further refine candidate ranking by integrating multiple predicted features, including MHC-binding profiles and antigenicity. Beyond classical pathogen antigens, environmental microbes can provide innate immune stimuli (e.g., flagellin, LPS) and novel secondary metabolites (e.g., rapamycin-like immunosuppressants), which can be predicted or discovered via metagenomics. We review current sequencing and immunoinformatic workflows - from gene calling to epitope prediction and Machine Learning-based ranking - applied to soil and related microbiomes. We highlight examples of known immunomodulators from soil microbes and discuss how Artificial Intelligence-driven design can accelerate mining of environmental microbiomes for biomedical targets. This integration of metagenomics and immunoinformatics promises a One Health perspective that explicitly links human, animal, and environmental health, expanding antigen discovery beyond gut- or pathogen-centric views, while highlighting computational strategies, limitations, and future directions of this approach.

Severe asthma is a complex disease that remains uncontrolled in many individuals despite optimized therapy. This chapter offers a comprehensive overview of the epidemiological and clinical burden of severe asthma, emphasizing the limitations of conventional phenotypic classifications. It highlights the transition toward molecular endotyping, where subtypes are defined by distinct biological pathways. Key findings from recent genomic, transcriptomic, and proteomic research are presented, identifying susceptibility loci and protein biomarkers linked to clinically relevant endotypes. Integrative case studies, such as those from the U-BIOPRED consortium, demonstrate how multi-omics approaches reveal eosinophilic and neutrophilic endotypes with specific immune and microbial signatures. The chapter also discusses data integration strategies, including consensus clustering and network fusion, as well as practical implications for biomarker discovery, personalized therapeutics, and future directions in precision asthma medicine.