Salvador Almagro-Moreno Lab

Diarrheal diseases are one of the main causes of child mortality, with millions affected worldwide. Cholera, a severe diarrheal disease caused by the bacterium Vibrio cholerae, remains a major scourge in areas with limited access to safe drinking water and sanitation. Over 120,000 deaths each year globally can be attributed to this diarrheal disease, with orders of magnitude more being unreported. To date, the factors controlling cholera outbreaks and cholera’s transmission remain poorly understood.

V. cholerae is a waterborne bacterium that serves as an ideal model system to study pathogen emergence. Most of the strains within the V. cholerae species pose no threat to human health; however, a phylogenetically confined group can cause cholera in humans even leading to global pandemics of the disease – a very rare feat among bacterial pathogens.

Over the past decades, our team has elucidated the genetic determinants that allow pathogenic strains of V. cholerae to cause outbreaks, colonize a host, and emerge as a human pathogen. We uncovered a set of genomic signatures present in environmental populations of bacteria, what we term virulence adaptive polymorphisms, that prime these microorganisms for pathogenicity before they acquire genes necessary for virulence and host colonization. Our work unearths the genetic origins of virulence traits and can be applied to other bacterial pathogens.  

Environmental changes significantly influence the spread and severity of infectious diseases. To better understand how ecological perturbations impact human health, our lab studies Vibrio vulnificus, a climate-sensitive emergent pathogen. Some strains of this aquatic microbe can cause deadly septicemia in humans with a mortality rate of over 50% in children, immunocompromised hosts and other susceptible groups. The infections occur through wound exposure to contaminated water or raw seafood. Concerningly, V. vulnificus outbreaks are becoming more frequent and are occurring in regions with no prior history of infection. To date, the specific genetic factors underlying the emergence of this pathogen are unknown and there is no effective vaccine targeting it. 

We are isolating and examining V. vulnificus strains from both endemic areas in the US and locations where new outbreaks have occurred. Our long-term studies demonstrated that specific ecological variables predict the existence of clones with pathogenic potential in environmental populations. Overall, our data showcase how environment shapes pathogenic potential and highlight the importance of integrating environmental data into public health strategies to develop early warning systems and broadly applicable control measures. 

Pathogen emergence is a hard to predict complex phenomenon that results from a non-linear combination of molecular changes, exposure to particular environmental conditions, and a multitude of unknown factors. By combining bioinformatics, bacterial ecology and molecular biology, our lab is building predictive models that allow researchers to forecast the emergence of virulent bacterial strains and their origins. Ultimately, our results are being used to inform translational studies that produce reliable therapeutic treatments against these bacterial threats.