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Abstract As observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes must occur in bacterial lineages, potentially allowing decomposition analysis to detect both disruption of DNA repair processes and exposure to niche-specific mutagens. Here we reconstruct mutational spectra for 84 clades from 31 diverse bacterial species and find distinct mutational patterns. We extract signatures driven by specific DNA repair defects using hypermutator lineages, and further deconvolute the spectra into multiple signatures operating within different clades. We show that these signatures are explained by both bacterial phylogeny and replication niche. By comparing mutational spectra of clades from different environmental and biological locations, we identify niche-associated mutational signatures, and then employ these signatures to infer the predominant replication niches for several clades where this was previously obscure. Our results show that mutational spectra may be associated with sites of bacterial replication when mutagen exposures differ, and can be used in these cases to infer transmission routes for established and emergent human bacterial pathogens.

Abstract Papaver genus, commonly known as popies, is a valuable source of alkaloids used in medicine, including papaverine, morphine, codeine, and thebaine. We isolated six endophytic fungal isolates producing morphinan alkaloids from four Papaver species growing in Kurdistan Province, Iran. To do this, a 1:1 mixture of methanol and chloroform was used to extract fungal cultures. The contents of morphinan alkaloids in the extracts were subsequently determined using phase high-performance liquid chromatography. Among the morphinan alkaloid-producing fungal isolates, IRAN 4653C had the highest yield giving 23.06 (mg/g) morphine and 2.03 (mg/g) codeine when grown in potato dextrose liquid medium. The identity of this isolate was examined and recognized as a new fungal species named as Pithoascus kurdistanesis sp. nov. based on multi-gene phylogenetic analyses of ITS, TEF-1α, and TUB2 sequences data and morphological features. The morphinan-producing endophytic fungus and the isolated Pithoascus species from Papaver are being reported for the first time. Accordingly, this fungus shows promise as a new source of valuable compounds which is illustrated and introduced here as a new Microascaceae member belonging to Pithoascus from Kurdistan Province, Iran. Moreover, the morphinan productivity of P. kurdistanesis was further validated by gas chromatography-mass spectrometry (GC–MS).

Abstract Severely-afflicted COVID-19 patients can exhibit disease manifestations representative of sepsis, including acute respiratory distress syndrome and multiple organ failure. We hypothesized that diagnostic tools used in managing all-cause sepsis, such as clinical criteria, biomarkers, and gene expression signatures, should extend to COVID-19 patients. Here we analyzed the whole blood transcriptome of 124 early (1–5 days post-hospital admission) and late (6–20 days post-admission) sampled patients with confirmed COVID-19 infections from hospitals in Quebec, Canada. Mechanisms associated with COVID-19 severity were identified between severity groups (ranging from mild disease to the requirement for mechanical ventilation and mortality), and established sepsis signatures were assessed for dysregulation. Specifically, gene expression signatures representing pathophysiological events, namely cellular reprogramming, organ dysfunction, and mortality, were significantly enriched and predictive of severity and lethality in COVID-19 patients. Mechanistic endotypes reflective of distinct sepsis aetiologies and therapeutic opportunities were also identified in subsets of patients, enabling prediction of potentially-effective repurposed drugs. The expression of sepsis gene expression signatures in severely-afflicted COVID-19 patients indicates that these patients should be classified as having severe sepsis. Accordingly, in severe COVID-19 patients, these signatures should be strongly considered for the mechanistic characterization, diagnosis, and guidance of treatment using repurposed drugs.

The emergence of multidrug resistance (MDR) in bacteria represents a global threat to human health. Here, Cazares et al. identify a family of MDR megaplasmids carrying large arrays of antibiotic resistance genes in Pseudomonas strains from various sources, including P. aeruginosa clinical isolates.

Aeromonas salmonicida subsp. salmonicida is a Gram-negative bacterium that causes furunculosis, a fish disease claiming substantial economic losses in the aquaculture industry. Major challenges exist in monitoring and controlling fish infections in aquaculture farms. Development of management practices to improve the sustainability of fish farming with disease prevention necessitates studies using well-defined systems and well-characterized bacterial isolates. Even though several A. salmonicida subsp. salmonicida genomes have been completely assembled and thoroughly annotated, in vivo pathogenicity data are lacking. Here we present A. salmonicida subsp. salmonicida 890054 as a prototype strain for standardized furunculosis challenges with survival data. Computational analysis of sequencing results provided a complete circular genome with annotations of plasmids carrying virulence factors, antimicrobial resistance, and secondary metabolite coding genes. The analysis also revealed the presence of an IncU plasmid distinct from other IncU plasmids previously associated with Aeromonas.