| Summary: | Deciphering the interactions between ticks and their microbiome is key to revealing new insights on tick biology and pathogen transmission. However, knowledge on tick-borne microbiome diversity and their contribution to drug resistance is scarce in sub–Saharan Africa (SSA), despite endemism of ticks. In this study, high-throughput 16S rRNA amplicon sequencing and PICRUSt predictive function profiling were used to characterize the bacterial community structure and associated antibiotic resistance markers in <i>Amblyomma variegatum</i>, <i>A. hebraeum</i><i>,</i> and <i>Hyalomma truncatum</i> ticks infesting Nguni cattle (<i>Bos</i> spp.). Twenty-one (seven families and fourteen genera) potentially pathogenic and endosymbiotic bacterial taxa were differentially enriched in two tick genera. In <i>H. truncatum</i> ticks, a higher abundance of <i>Corynebacterium</i> (35.6%), <i>Porphyromonas</i> (14.4%), <i>Anaerococcus</i> (11.1%)<i>, Trueperella</i> (3.7%), and <i>Helcococcus</i> (4.7%) was detected. However, <i>Rickettsia</i> (38.6%), <i>Escherichia</i> (7%), and <i>Coxiellaceae</i> (2%) were the major differentially abundant taxa in <i>A</i>. <i>variegatum</i> and <i>A. hebraeum</i>. Further, an abundance of 50 distinct antibiotic resistance biomarkers relating to multidrug resistance (MDR) efflux pumps, drug detoxification enzymes, ribosomal protection proteins, and secretion systems, were inferred in the microbiome. This study provides theoretical insights on the microbiome and associated antibiotic resistance markers, important for the design of effective therapeutic and control decisions for tick-borne diseases in the SSA region.
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