Abstract Blood inside mammals is a forbidden area for the majority of prokaryotic microbes; however, red blood cells tropism microbes, like “vampire pathogens” (VP), succeed in matching scarce nutrients and surviving strong immunity reactions. Here, we found VP of Mycoplasma , Rhizobiales and Rickettsiales showed significantly higher counts of (AG) n dimeric simple sequence repeats (Di-SSRs) in the genomes, coding and non-coding regions than non Vampire Pathogens (N_VP). Regression analysis indicated a significant correlation between GC content and the span of (AG) n -Di-SSR variation. Gene Ontology (GO) terms with abundance of (AG) 3 -Di-SSRs shared by the VP strains were associated with purine nucleotide metabolism ( FDR <  0.01), indicating an adaptation to the limited availability of purine and nucleotide precursors in blood. Di-amino acids coded by (AG) n -Di-SSRs included all three six-fold code amino acids (Arg, Leu and Ser) and significantly higher counts of Di-amino acids coded by (AG) 3 , (GA) 3 and (TC) 3 in VP than N_VP. Furthermore, significant differences ( P <  0.001) on the numbers of triplexes formed from (AG) n -Di-SSRs between VP and N_VP in Mycoplasma suggested the potential role of (AG) n -Di-SSRs in gene regulation.