Response of Vibrio cholerae to Low-Temperature Shifts: CspV Regulation of Type VI Secretion, Biofilm Formation, and Association with Zooplankton

The ability to sense and adapt to temperature fluctuation is critical to the aquatic survival, transmission, and infectivity ofVibrio cholerae , the causative agent of the disease cholera. Little information is available on the physiological changes that occur whenV. cholerae experiences temperature shifts. The genome-wide transcriptional profile ofV. cholerae upon a shift in human body temperature (37°C) to lower temperatures, 15°C and 25°C, which mimic those found in the aquatic environment, was determined. Differentially expressed genes included those involved in the cold shock response, biofilm formation, type VI secretion, and virulence. Analysis of a mutant lacking the cold shock genecspV , which was upregulated >50-fold upon a low-temperature shift, revealed that it regulates genes involved in biofilm formation and type VI secretion. CspV controls biofilm formation through modulation of the second messenger cyclic diguanylate and regulates type VI-mediated interspecies killing in a temperature-dependent manner. Furthermore, a strain lackingcspV had significant defects for attachment and type VI-mediated killing on the surface of the aquatic crustaceanDaphnia magna . Collectively, these studies reveal thatcspV is a major regulator of the temperature downshift response and plays an important role in controlling cellular processes crucial to the infectious cycle ofV. cholerae .IMPORTANCE Little is known about how human pathogens respond and adapt to ever-changing parameters of natural habitats outside the human host and how environmental adaptation alters dissemination.Vibrio cholerae , the causative agent of the severe diarrheal disease cholera, experiences fluctuations in temperature in its natural aquatic habitats and during the infection process. Furthermore, temperature is a critical environmental signal governing the occurrence ofV. cholerae and cholera outbreaks. In this study, we showed thatV. cholerae reprograms its transcriptome in response to fluctuations in temperature, which results in changes to biofilm formation and type VI secretion system activation. These processes in turn impact environmental survival and the virulence potential of this pathogen.