The formation of the massive deletion of genes called “black holes,” which are detrimental to a pathogenic lifestyle, provides a bacterial evolutionary route that permits a pathogen to augment virulence and host-adaptability. For example, cadaverine substrate has inhibitory effects on the enterotoxin activity of the Shigella species. Therefore, the encoding gene of the lysine decarboxylase enzyme (CadA gene) as an anti-virulence gene is deleted from the genome of the Shigella. This and other similar cases in bacteria can be used for antitoxin therapy. Hence, identification of the role of black holes in the pathogenic evolution of bacteria output could possibly lead to novel treatments of infectious diseases in human beings. Here, we reviewed different types of pathoadaptation mutations among pathogens. Cases of black holes among the important human bacterial pathogens included Shigella, Rickettsiae, Mycobacterium leprae, Burkholderia, Bordetella, and Chlamydia. We found that the most prevalent pathoadaptive pathway among bacteria was the gene inactivation or deletion route.