Kosakonia radicincitans with hypervirulent lON genes causes human bloodstream infections - supplementary - materials

Kosakonia radicincitans is a species within the new genus Kosakonia, which is typically a plant pathogen, with rare reports of human infection. The number of human infections may be underestimated because this new genus is under-represented among diagnostic tools. This report describes a case of bloodstream infection caused by K. radicincitans. The pathogen was identified by matrix-assisted laser desorption/ionization-TOF mass spectrometry and 16S rRNA gene sequencing. The hypervirulent human pathogenicity gene LON, which has not been described before, was detected in the bacterial genome by gene annotation. Thus, this discovery provides a new reference for studying the pathogenic mechanism of this rare pathogen.</p

Comparison of the numbers of mutated genes in exonic regions, and ratio to total mutations detected by WES in 11 EBV+ DLBCL cases according to age and pathological subtype.

Comparison of the numbers of mutated genes in exonic regions, and ratio to total mutations detected by WES in 11 EBV+ DLBCL cases according to age and pathological subtype.</p

Signatures of mutational processes and intratumor clonal heterogeneity of EBV+ DLBCL cases.

The DeconstructSigs method was applied, which uncovered four mutational signatures (Fig 4A), including signatures 3, 5, 12, and 30. Among these signatures, signature 3 was the main type. MATH scores were used to evaluate intratumor clonal heterogeneity (Fig 4B), revealing allele frequency distribution values of between 47 and 86 for the tumors.</p

Clinicobiological features of the 11 EBV+ DLBCL patients analyzed by whole-exome sequencing (WES).

Clinicobiological features of the 11 EBV+ DLBCL patients analyzed by whole-exome sequencing (WES).</p

Patient characteristics at diagnosis of EBV+ DLBCL (11 cases).

Patient characteristics at diagnosis of EBV+ DLBCL (11 cases).</p

The 30 most commonly mutated genes from selected variants in EBV+ DLBCL identified by whole-exome sequencing.

Based on the total number of all mutation loci within one somatic mutated gene in a detected region (exonic region, intronic region, intergenic region, UTR, and other regions), the top 5 most frequently mutated genes were MUC16, PRSS3, MUC19, MUC3A, and RLIM in decreasing order.</p

Distribution of mutations in different genome regions of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma detected by whole-exome sequencing.

(A) The percentages of mutations in different regions of EBV+ DLBCL cases. The percentage of mutations in exonic regions ranged from 3.49%–22.68% among these 11 cases. (B) We identified 3326 protein-coding genes with somatic mutations affecting exonic regions, with a range from 200 to 410 per case.</p

Mutation spectrum of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma shown by whole-exome sequencing.

Frequency of substitutions in each sample for the six possible classes of mutation. The most common substitution was the transition C>T/G>A, followed by T>C/A>G.</p

Relationship between clinical variables and MATH scores and OS in 11 EBV+ DLBCL cases.

Relationship between clinical variables and MATH scores and OS in 11 EBV+ DLBCL cases.</p

An overview of the data analysis strategy for single-nucleotide variations (SNVs) and indels shown by whole-exome sequencing.

On average, we identified 220 (range, 126–358) somatically acquired point mutations per case. Of these, an average of 168 (range, 105–252) were non-synonymous and 81 (range, 52–149) were synonymous. Thus, the ratio of non-synonymous to synonymous was 2.08 (0.95–2.67) mutations per Mb.</p