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Why Is the Current Cholera Pandemic Lasting So Long?

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The bacterium Vibrio cholerae is the causative agent of the diarrheal disease cholera and is responsible for seven known pandemics. The seventh cholera pandemic began in 1961 and is still active. Unlike previous pandemics, it is caused by cholera strains of a slightly different type. How did the modified cholera strains develop and spread, and what might have contributed to their success? Scientists from the Max Planck Institute for Evolutionary Biology in Plön, Germany, and CAU Kiel, in an international team with colleagues from City College New York and the University of Texas Rio Grande Valley, have now gained new insights into a molecular mechanism that provides insight into the interactions between cholera bacteria and may have played a role in the emergence of the seventh pandemic.

In their natural environment, bacteria are subject to competition with other bacteria for space and nutrients. In this process, molecular mechanisms help them to hold their own. One such mechanism is the so-called "type 6 secretion system" (T6SS), with which a bacterium transports toxic proteins into a neighboring bacterium and thereby kills it. Thus, cholera bacteria of the seventh pandemic use their T6SS to keep other bacteria in check and presumably more easily cause infection.

Researchers now had the special opportunity to study the T6SS of cholera bacteria from previous pandemics. For this purpose, among other things, the T6SS genome sequence of cholera bacteria from the 2nd pandemic was reconstructed from a museum specimen from the 19th century in a complex procedure and recreated in the laboratory.

In the process, the scientists were able to show that 2nd and 6th pandemic cholera bacteria lack a functional T6SS. As a result, the bacteria of earlier pandemics not only lack the ability to attack other bacteria, they are themselves killed by bacterial strains of the seventh pandemic. This may have been one of the reasons that older cholera strains were displaced by modified cholera strains of the seventh pandemic and are now hard to find.

Data from new lab

Daniel Unterweger, one of the study's authors and a group leader at the Max Planck Institute in Plön, Germany, says: "With these findings, we support the theory that microbial competition between bacteria is very important for understanding pathogens and bacterial pandemics. Our research on the cholera bacterium was made possible by an S2 laboratory newly established at the institute. Here, we can conduct experiments with bacterial pathogens under the necessary safety precautions. The study contains some of the first data from the new laboratory."


Kostiuk B, Santoriello FJ, Diaz-Satizabal L, et al. Type VI secretion system mutations reduced competitive fitness of classical Vibrio cholerae biotype. Nat Commun. 2021;12(1):6457. doi:10.1038/s41467-021-26847-y

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