Vibrio cholerae (V. cholerae), the causative agent of cholera, experiences a wide range of temperatures. These include seasonal and inter-annual temperature changes in the aquatic environment (ranging between 12 and 30°C) and the temperature of the human host (37°C). Once inside the host, the shift to the higher temperature regulates virulence gene expression, making adaptation to temperature important for both survival in the environment and infection. Now, scientists have discovered an essential protein that allows them to adapt to changes in temperature. The protein, BipA, is conserved across bacterial species, which suggests it could hold the key to how other types of bacteria change their biology and growth to survive at suboptimal temperatures.

This work is published in eLife in the article, “BipA exerts temperature-dependent translational control of biofilm-associated colony morphology in Vibrio cholerae.”

V. cholerae is the bacteria responsible for the severe diarrheal disease cholera. As with other species, V. cholerae forms biofilms—communities of bacteria enclosed in a structure made up of sugars and proteins—to protect against predators and stress conditions. V. cholerae forms these biofilms both in their aquatic environment and in the human intestine. There is evidence to suggest that biofilm formation is crucial to V. cholerae’s ability to colonize in the intestine and might enhance its infectivity.

V. cholerae experiences a wide range of temperatures and adapting to them is not only important for survival in the environment but also for the infection process,” explained lead author Teresa del Peso Santos, PhD, a postdoctoral researcher at the Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Sweden. “We know that at 37°C, V. cholerae grows as rough colonies that form a biofilm. However, at lower temperatures, these colonies are completely smooth. We wanted to understand how it does this.”

The authors showed that colony rugosity, a biofilm-associated phenotype, is regulated by temperature in V. cholerae strains that naturally lack the master biofilm transcriptional regulator HapR.

The researchers screened the microbes for genes known to be linked with biofilm formation. They found a marked increase in the expression of biofilm-related genes in colonies grown at 37°C compared with 22°C.

To find out how these biofilm genes are controlled at lower temperatures, they generated random mutations in V. cholerae and then identified which mutants developed rough instead of smooth colonies at 22°C. They then isolated the colonies to determine which genes are essential for switching off biofilm genes at low temperatures.

The most common gene they found is associated with a protein called BipA. As anticipated, when they intentionally deleted BipA from V. cholerae, the resulting microbes formed rough colonies typical of biofilms rather than smooth colonies. This confirmed BipA’s role in controlling biofilm formation at lower temperatures.

To explore how BipA achieves this, the researchers compared the proteins produced by normal V. cholerae with those produced by microbes lacking BipA, at 22°C and 37°C. They found that BipA alters the levels of more than 300 proteins in V. cholerae grown at suboptimal temperatures, increasing the levels of 250 proteins including virtually all known biofilm-related proteins. They also showed that at 37°C, BipA adopts a conformation that may make it more likely to be degraded. In BipA’s absence, the production of key biofilm regulatory proteins increases, leading to the expression of genes responsible for biofilm formation.

These results provide new insights into how V. cholerae adapts to temperature and will help understand—and ideally prevent—its survival in different environments and transmission into humans.

“We have shown that BipA is critical for temperature-dependent changes in the production of biofilm components and alters colony shape in some V. cholerae strains,” concluded senior author Felipe Cava, PhD, associate professor at the department of molecular biology, and MIMS group leader and Wallenberg Academy Fellow, Umeå University. “Future research will address the effect of temperature- and BipA-dependent regulation on V. cholerae during host infection and the consequences for cholera transmission and outbreaks.”

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