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Abstract We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

Abstract Tick-borne infections, including those of bacterial origin, are significant public health issues. Antimicrobial resistance (AMR), which is one of the most pressing health challenges of our time, is driven by specific genetic determinants, primarily by the antimicrobial resistance genes (ARGs) of bacteria. In our work, we investigated the occurrence of ARGs in the genomes of tick-borne bacterial species that can cause human infections. For this purpose, we processed short/long reads of 1550 bacterial isolates of the genera Anaplasma (n = 20), Bartonella (n = 131), Borrelia (n = 311), Coxiella (n = 73), Ehrlichia (n = 13), Francisella (n = 959) and Rickettsia (n = 43) generated by second/third generation sequencing that have been freely accessible at the NCBI SRA repository. From Francisella tularensis, 98.9% of the samples contained the FTU-1 beta-lactamase gene. However, it is part of the F. tularensis representative genome as well. Furthermore, 16.3% of them contained additional ARGs. Only 2.2% of isolates from other genera (Bartonella: 2, Coxiella: 8, Ehrlichia: 1, Rickettsia: 2) contained any ARG. We found that the odds of ARG occurrence in Coxiella samples were significantly higher in isolates related to farm animals than from other sources. Our results describe a surprising lack of ARGs in these bacteria and suggest that Coxiella species in farm animal settings could play a role in the spread of AMR.