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The etiological agent of cholera, a severe diarrheal disease that can occur as an epidemic or sporadic disease, is Vibrio cholera. The V. cholera O1 and O139 serogroups that cause the cholera pandemic originated in the Indian subcontinent and have since spread around the world, killing millions of people each year, mostly in poor and disadvantaged nations. V. cholera O1 may generate biotype-specific cholera toxin and is further characterized as classical and El Tor biotypes. The present seventh pandemic El Tor strains have been replacing the sixth pandemic strains since 1961, resulting in the classical biotype strain that generates classical CT. The major issue is the continuous emergence of Atypical El Tor V. cholera srains encoding classical CT. The global threat of atypical El Tor V. cholera srains encoding classical CT is real. These Atypical El Tor strains have much more severe pathophysiology than El Tor or conventional strains. V. cholera pathogenesis is a complicated process that includes the coordinated expression of many virulence-associated genes to induce illness. We still don’t know everything about V. cholera’s virulence profile, including the direct and indirect expression of genes involved in the parasite’s survival and stress adaption in the host. Whole genome sequencing has paved the way for a better understanding of the evolution and distribution of infectious pathogens, as well as outbreak detection and pathogen surveillance for the implementation of direct infection control measures in the clinic against many infectious pathogens, including V. cholera, in recent years.