Mathias T. Rosenfeldt

Bacterial prostatitis caused by uropathogenic Escherichia coli (UPEC) strains is a highly prevalent and recurrent infection responsible for significant morbidity in men. The molecular pathogenesis of prostatitis remains poorly understood, partly due to a lack of suitable in vitro models. Here we developed a 2D mouse stem cell-derived prostate epithelial organoid model. In the organoid model, 5α-dihydrotestosterone promoted differentiation of basal into luminal cells, while transcriptomic analyses validated the model in comparison to 3D models and mouse prostate tissue. Infection analyses revealed that UPEC preferentially attached to, invaded and replicated within luminal prostate cells. Experiments with a UPEC mutant strain lacking the bacterial adhesin, FimH, alongside immunoprecipitation, mass spectrometry, biochemistry and infection experiments with host gene knockouts revealed that FimH–prostatic acid phosphatase (PPAP) binding interactions promote UPEC invasion of luminal prostate cells. ᴅ -Mannose competitively inhibited FimH–PPAP interactions. Findings were validated using ex vivo human prostate tissue. These data highlight the adaptability of FimH in engaging host receptors and the potential for FimH-targeting strategies to reduce bacterial prostatitis.

Supplementary Figure S6 shows copy number dynamics in EGFR-amplified glioblastoma samples

Supplementary Figure S1 characterises the MYCN amplification status, copy number heterogeneity and growth behaviour in neuroblastoma samples

Supplementary Table S4 contains information about the MYCN status of neuroblastoma patient samples used in Figure 1 and Supplementary Figure 1

Supplementary Figure S2 shows simulation results of clonogenic assays under copy number-dependent and -independent cell fitness

Supplementary Figure S3 demonstrates how MYC(N) dosage differences drive phenotypic heterogeneity in ecDNA-containing cancers

Supplementary Table S1 contains FISH proteomics datasets

Supplementary Figure S4 provides computational and experimental models of ecDNA-dependent treatment responses in neuroblastoma

Supplementary Table S2 lists the GDCS compounds used in Supplementary Figure S4L

Supplementary Figure S8 illustrates how one-two punch, senolytic therapies can be used to target tumor cells with low MYCN copy numbers