Mostly Microbes and Infection - by David Ojcius

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