EGH Research Associate Professor, Dr. Afsar Ali, discusses a novel “persister” Vibrio cholerae that may promote cholera transmission from aquatic reservoirs to humans

Figure 1

Cholera continues to be a major public health threat, particularly in countries where clean drinking water, adequate sanitation and hygiene are not optimal. Toxigenic Vibrio cholerae, a gram negative curved rod bacterium (Figure 1) with a singular polar flagellum, is responsible for the epidemics of cholera. Aquatic reservoirs, including fresh, estuarine and marine waters primarily serve as reservoirs of V. cholerae and humans acquire the bacterium upon the consumption of contaminated water. Despite its ubiquity in aquatic reservoirs, the genetic and physiologic basis of persistence of V. cholerae in those reservoirs is not clearly understood in spite of decades of research.

To this context, there are currently two schools predominating thought: (a) first— in response to cold and nutrient starvation, V cholerae can enter into a viable but non-culturable (VBNC) state that can revert to culturable form upon nutrient enrichment and warm temperature.


However, the mechanism(s) of resuscitation of VBNC V. cholerae into culturable form and the association of VBNC to cholera epidemics remains to be elucidated; (b) second— a smooth colony variant of V. cholerae can switch to “rugose” colony variant associated with copious amount of exopolysaccharide production that confers resistance to harsh environmental conditions. However, only ~15% of V. cholerae strains can switch to rugose variant with well-designed laboratory conditions. Taken together, current available studies suggest that V. cholerae may employ other mechanism(s) for its environmental persistence.

In keeping with this conundrum, Dr. Afsar Ali hypothesized that a subset of culturable V. cholerae can persist in the aquatic reservoirs as “persister” cells; these “persister” cells can cause epidemics regularly in cholera endemic countries. In response to stress, many bacterial pathogens can select for a subpopulation of “persister” cells by stochastic mechanism(s). Consistent with his hypothesis, Dr. Ali has recently demonstrated that in response to nutrient starvation a subpopulation of culturable V. cholerae indeed assumed a “persister” phenotype in nutrient-poor lake water microcosm model (Jubair et al., September 2012, PLoS ONE, doi:10:1371). Interestingly, the “persister” V. cholerae rendered to canonical V. cholerae on nutrient supplementation, including chitin and phosphate.

As depicted (Figures 2 and 3), during the “persister” formation, V. cholerae exhibited diverse morphologies, including long helical cells with bipolar flagella, and small rod-shaped cells with peritrichous flagella. Dr. Ali is currently studying the underlying genetic mechanism(s) promoting persister formation. He is also investigating if the “persister” cells contribute to the emergence of cholera index case. Dr. Ali’s research also focuses on the ecology, epidemiology, evolution, and biofilm of V. cholerae as well as cholera disease transmission.

View Dr. Ali’s faculty profile.