Mostly Microbes and Infection - by David Ojcius

Summary Antibiotics are among medicine’s greatest successes, but resistance evolution threatens their continued efficacy. Decades of research have deepened our understanding of the mechanisms and evolutionary dynamics of antimicrobial resistance. More recently, advances in machine learning (ML) and artificial intelligence (AI) show promise in predicting antimicrobial resistance in pathogens based on rapid whole-genome sequencing and other accessible data. In this perspective, we highlight advances in understanding the mechanisms and spread of antimicrobial resistance. We discuss how this knowledge, coupled with ML- and AI-based approaches, can inform the prediction of resistance and a precision-medicine strategy that targets pathogenic bacteria specifically, thereby limiting resistance evolution and collateral damage to the microbiome. These accurate predictions of bacterial vulnerabilities will enable the adaptation of classical antimicrobial treatments with adjuvants, as well as the ...

Highlights • Halococci differ from other haloarchaea by their thick cell wall structure. • Currently no viruses are known to infect Halococci. • Seven novel Halococcus strains were characterized and the genomes sequenced. • The novel Halococcus strains contain predicted anti-viral defence mechanisms. • Detected proviruses indicate that Halococci are infected by viruses in nature.

Highlights • Lysine phenylacetylation (Kpaa) is a diet- and gut microbiota-derived PTM • Kpaa is enriched in mitochondria and regulated by SIRT3 • High Kpaa impairs mitochondrial function and correlates with MASH • K481 phenylacetylation of HSP60 leads to the mitochondrial unfolded protein response

Highlights • Gut microbiome CRC signature is universal across age groups and sequencing approaches • Tumor-enriched microbes are concordant with fecal CRC signatures • Increasing dietary fiber intake reduces the microbiome CRC signature score • Fusobacterium subspecies show biogeographic variation in CRC enrichment

Highlights • Climate stressors restructure soil microhabitats, reassembling microbial guilds that regulate C–N–P cycling and resilience. • Cross-domain feedbacks link pore architecture and soil chemistry to microbiome functions and emergent soil health outcomes. • Rhizosphere mechanisms (exudates, siderophores, ACC deaminase, ISR, AMF/N-fixing symbioses) provide actionable leverage points under stress. • Integrative indicators connect physical, chemical, and biological metrics to soil multifunctionality for monitoring under climate extremes. • Emerging tools (meta-omics, 3D imaging, spectroscopy, isotopic tracing, in situ sensors) enable mechanistic diagnosis and decision support.

Highlights • CBASS antagonizes phage replication while preserving cell viability in P. aeruginosa • 3′,3′-cGAMP-activated CapV targets diverse phages and overcomes CBASS inhibitors • CBASS-sensitive phages transcribe and replicate their genome • CBASS activity limits packaged phage DNA, reducing virion production

Highlights • Isolated TPD-causing V. parahaemolyticus strain P40.49 from infected shrimp. • Experimental infection confirmed the pathogenicity of the TPD-causing strain P40.49. • Whole genome sequencing confirmed the presence of ∼69 kbp TPD-associated plasmid. • The shrimp stomach and intestine tissues are ideal for early TPD detection (6 hpi). • Four unique TPD-associated genes may serve as additional markers for TPD detection.

Highlights • W. chondrophila encodes two Ndk paralogs, unlike most Chlamydiota. • ndk genes are early expressed and protein levels peak during bacterial replication. • WcNdk1 is inclusion-bound, while WcNdk2 localizes to host cell compartments. • AZT inhibits bacterial growth and protects host cells from infection-induced death. • AZT sensitivity is linked to ndk2 presence, implicating WcNdk2 as functional target.

Highlights • Adjunctive oral FMT accelerates antidepressant response as early as week 2 • Superior efficacy persists through 8 weeks with no additional side effects • FMT reshapes gut microbes, with donor strains coexisting in recipients • Benefits are mediated by elevated bile acids and reduced systemic inflammation

Highlights • YprA-family helicases are a central hub in the prokaryotic defense system network • YprA phylogeny analysis identifies a distinct class of defense systems called ARMADA • ARMADA protects bacteria against diverse phages and synergizes with Druantia III • ARMADA, Druantia III, and Zorya II co-occur in phage-like integrated elements

This Special Issue aims to bring together cutting-edge research and reviews that integrate omics data, metabolic network analysis, and ecological perspectives to elucidate microbial mechanisms involved in xenobiotic degradation and detoxification. Contributions will highlight novel enzymes and pathways, microbial community dynamics, metabolic engineering strategies, and real-world applications in environmental remediation and industrial biotechnology.

Highlights • 502M nonredundant genes from 2,138 deep-sea samples reveal unprecedented diversity • Deep-sea microbes’ DNA maintenance genes rapidly evolve with specialized properties • Deep-sea protein fold catalog with 392 novel domains aids structure-guided mining • A structure-mined deep-sea helicase enhances nanopore DNA sequencing speed

Highlights • Secondhand smoke (SHS) exposure significantly alters the ocular surface microbiome (OSM) in children aged 3–18 years. • Microbial diversity is significantly reduced on ocular surface in SHS-exposed children. • Beneficial commensal taxa are depleted in SHS-exposed children. • Environmental stress-related metabolic pathways and immune-related pathways are significantly altered in SHS-exposed children.

Highlights • Disinfectants trigger adaptive, strain-specific responses in Arcobacter butzleri. • Overexpression of AMR and virulence genes in A. butzleri. • Antibiotics induced limited transcriptomic changes.

Highlights • Antibodies direct viruses and bacteria for post-infection xenophagy • TRIM21 regulates ADX via its ubiquitination activity • ADX protects against pathogenic Salmonella infection in vivo

Highlights • Mucin modulates phage-host dynamics in Yersinia enterocolitica. • Temperature and nutrient availability further shape phage infection outcomes. • Bacterial pre-exposure to mucin leads to 2-log increase in phage titers. • Mucin supplementation reduces biofilm formation in all tested conditions. • Phage-resistant variants carry mutations in metabolism, quorum sensing, antimicrobial resistance genes.

Highlights • HCAs dominate meconium (>50%) as primary bile acids produced by fetal CYP3A7 • HCAs shape intestinal immune tolerance by promoting Treg cells and suppressing Th17 cells • High neonatal HCAs protect against gastrointestinal disorders and infections

Highlights • Respiratory growth with cysteine increases H 2 S production in U. maydis. • Endogenous H 2 S promotes mitochondrial biogenesis and metabolic remodeling . • H 2 S shifts respiration toward alternative oxidase-dependent electron transport . • Elevated H 2 S increases global protein S-sulfenylation and S-persulfidation. • Endogenous H 2 S modulates disease severity during maize infection.