Plant pathogenic bacteria of the genera Erwinia, Pseudomonas, Ralstonia, Pantoea and Xanthomonas cause diverse diseases in various crops. The molecular basis that partially explains the pathogenicity of these bacteria resides in the translocation of effector proteins into the interior of host cells through the type three secretion system (TTSS). Xanthomonas axonopodis pv. manihotis (Xam) is a gram negative bacillus and is the causal agent of cassava (Manihot esculenta Crantz) bacterial blight. Studies derived from the genomic sequencing of different Xam strains has allowed the identification of hrp-associated F (HpaF) as a principal effector present in all sequenced strains from Latin America, Africa, and Asia. In this study we evaluated the importance of HpaF in Xam virulence using two strategies. First, we could determine histologically morphological changes in cassava cells causes by HpaF. Second, a comparative transcriptomic approach was used employing microarrays of cassava ADNc and RNA obtained from cassava plants inoculated with strains of Xam mutated in hpaF (ΔhpaF) or complemented (ΔhpaF +hpaF). The data obtained suggest that HpaF is a virulence factor in Xam since it negatively regulates genes involved in the metabolism and defense of the plant.