Mostly Microbes and Infection - by David Ojcius

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.

Highlights • Epigenetic phase variations (ePVs) are prevalent in the human gut microbiome • Long- and short-read metagenomic data reveal ePVs associated with antibiotics and FMT • An ePV in an A. muciniphila strain regulates mucC , enhancing tolerance to amoxicillin • ePV creates intra-strain heterogeneity, enhancing bacterial adaptation via bet-hedging

Highlights • CRKP-derived outer membrane vesicles (OMVs) serve as multifunctional vectors for antibiotic resistance, encapsulating a diverse array of lipids and harboring the carbapenemase gene bla KPC . • Meropenem stress triggers a marked upregulation of membrane lipids in CRKP-OMVs, particularly sphingolipids (SP), glycerolipids (GL), glycerophospholipids (GP), and fatty acids (FA), which likely fortify bacterial antibiotic resistance through enhanced membrane stability and efflux efficiency. • CRKP-OMVs mediate horizontal gene transfer of bla KPC-2 to both intra- and interspecies susceptible bacteria, with meropenem-induced lipid remodeling significantly boosting transformation efficiency—a potential accelerator for environmental resistance spread.

Highlights • Incidence of CCPD rose to 9.04 per 100,000 population in the post-pandemic 2024. • Lower β-lactam susceptibility of the pneumococcal isolates is due to serotype shift. • Resistant non-PCV13 clones are emerging from clonal expansion and capsular switch.

Highlights • Organic acid-based DESs act against colistin- and methicillin-resistant strains. • T-glycoline–nanoparticle mix enhances activity against MRSA. • Organic DESs eliminate mature biofilms and damage bacterial cells. • T-glycoline and oxaline reduce titres of enveloped and non-enveloped viruses. • Nanoparticles enhance the safety of DESs.

HIGHLIGHT • Cyclic-di-AMP is a non-canonical driver of methicillin resistance in MRSA • Sub-MIC methicillin and biofilms elevate c-di-AMP via DacA upregulation • Elevated c-di-AMP activates STING and skews macrophage responses • FDA approved drugs Tropinone and eucalyptol identified as DacA inhibitors • DacA inhibition restores β-lactam susceptibility in MRSA

Highlights • HSI#6 is a rapid, micromolar, broad-spectrum bacteriostatic agent. • Triggers immediate, multi-pathway cell envelope stress responses. • Drives temporal omics reprogramming toward metabolic shutdown. • Shows transcriptomic similarity to ionophores yet a distinct MOA. • Exhibits low resistance evolution with compensatory topA mutations.

Highlights • Vitamin B12 induces stable small-colony variants (SCVs) in CRAB. • SCVs exhibit reduced cefiderocol killing and regrowth. • Mutations affect iron uptake, envelope structure, and metabolism. • Co-exposure enriches SCVs with siderophore and BfmRS changes. • Nutrients modulate antibiotic efficacy and persistence in CRAB.

Highlights • soxR mutations cause constitutive activation of SmeVWX and MfsA efflux pumps. • Mutations in soxR confer resistant to levofloxacin, a drug option for S. maltophilia. • Single R49 substitution activates SoxR and drives multidrug resistance.

Highlights • Smolstatin1 clusters with other myxozoan cystatin-like stefins • Smolstatin1 is upregulated during sporogony and localizes to cell compartments and parasite surface • Smolstatin1 inhibits host and parasite cysteine proteases, mainly cathepsin L • RNAi-mediated Smolstatin1 knockdown impairs parasite motility and alters cell morphology • Smolstatin1 crystallizes as an unusual domain-swapped dimer

  Highlights • 76 endophytic bacteria were isolated from Halocnemum strobilaceum from Murcia (Spain). • Most isolates (96.05%) exhibited plant growth-promoting traits in vitro . • Selected strains in a consortium enhanced Medicago sativa growth under salinity stress. • Four novel species for agricultural biotechnological applications were described.

Highlights • First experimental validation for anti-MPXV activity of BTE and BBE • BTE/BBE exert synergistic antiviral effects when combined mutually or with 3HP-β-LG • Broadens the source diversity of antiviral agents against orthopoxviruses • BTE and BBE have promising application in high-risk and resource-limited regions

Highlights • Dietary soy enhances L. reuteri and M. intestinale colonization in the small intestine • Dietary soy promotes Tfh cell and IgA responses in the Peyer’s patches of weaning mice • L. reuteri provides cognate antigens, while M. intestinale drives IL-1β production • Soy-induced IgA is polyreactive and protects against Salmonella infection

Highlights • CheW2 negatively regulated the expression of outer membrane proteins in V. splendidus • ClpP degraded CheW2 based on the recognization of its AA motif at the N terminal • Pseudoalteromonas sp. H2 attenuated the expression of clpP gene of V. splendidus AJ01

Highlights • Sesame-flavor Baijiu fermentation was performed using different sorghum varieties. • Microbial interactions affected volatile formation differently in sorghum varieties. • Cultivar-specific physicochemical traits modulate microbial consortia structure. • Sorghum selection can format flavor paradigm and standardize Baijiu quality.

Highlights • This study systematically analyzed alterations in the ocular surface microbiome of patients with progressive supranuclear palsy-Richardson’s syndrome (PSP-RS) via metagenomic sequencing, with comparisons to Parkinson’s disease (PD) patients and healthy controls (HC). • The β-diversity of the ocular surface microbiome in PSP-RS patients was significantly altered compared to HC, while no such obvious difference was observed in PD patients. PSP-RS patients exhibited increased abundances of g_Acinetobacter and g_Anaerococcus, decreased abundance of g_Vibrio, as well as characteristic changes at the specific species (e.g., s_Acinetobacter_guillouiae) and strain levels. • The ocular surface microbiome of PSP-RS patients showed more significant remodeling in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways, involving multiple key pathways such as transposase activity and amino acid metabolism. • The abundance of g_Acinetobacter was positiv...

Highlights • The  S. maltophilia  MntH importer contributes to H 2 O 2  resistance and intracellular survival • The Mn exporter MntP limits toxicity even at sub-inhibitory Mn²⁺ concentrations • The  S. maltophilia  MntR regulated genes include the extracytoplasmic TBDR-pTFP module • The TBDR-pTFP locus is specifically induced under combined Mn 2+  and Fe 2+  limitation • S. maltophilia  Mn homeostasis is linked to iron availability and oxidative stress responses

Highlights • Bifidobacterium stercoris  KC84 alleviates IBS-D-like symptoms in mouse and rat models • KC84 modulates serotonin-related pathways associated with diarrhea • KC84 induces IFN-β production from colonic dendritic cells • IFN-β is associated with reduced intestinal smooth muscle contractility

Highlights • Maternal helminths promote offspring antiviral immunity via the microbiota • Helminth-altered microbiota produce IPA, which drives antiviral protection • IPA induces lung epithelial type I interferon responses to promote antiviral immunity • Helminth-endemic human microbiota are enriched in the tryptophan metabolism pathway