In a recent publication in PNAS, researchers have revealed an intriguing similarity between Vibrio cholerae, the causative agent of the life-threatening disease cholera, and Marinomonas primoryensis, a bacterium adapted to extreme cold environments. Both species share a protein with divergent functions: in one, it facilitates cholera infection, while in the other, it enables binding to aquatic microorganisms, enhancing their survival strategies.

Cholera is a highly contagious bacterial infection caused by Vibrio cholerae, characterized by severe diarrhea leading to rapid dehydration and making it a potentially life-threatening disease. V. cholerae is a bacterium naturally found in aquatic environments, where it forms thriving communities. This propensity explains why the consumption of contaminated water plays a pivotal role in the transmission of cholera. 

V. cholerae expresses a protein fragment essential for infection

The bacterium's entry into the human body is facilitated by a protein called flagellar-regulated hemagglutinin A (FrhA). This substantial protein, belonging to the "adhesins" protein family, is crucial for initiating infection. When FrhA is produced within the bacterium, it is partially secreted to the exterior but remains anchored to V. cholerae's outer membrane. This anchoring is due to one end of the protein forming a "plug" too large to pass through the membrane pore connecting to the outside.

In their research, the authors identified the different regions constituting this protein, including a "peptide-binding domain" (PBD), a feature also present in Marinomonas primoryensis. Intriguingly, when they created mutants of the bacterium lacking this specific PBD, they observed that the resulting bacteria still expressed the FrhA protein but lost their hemagglutination activity. This suggests that while PBD is not essential for FrhA, it is necessary for interacting with red blood cells.

As V. cholerae colonizes epithelial cells during infection, the researchers conducted flow cytometry tests to assess the role of PBD in this process. This technique allowed them to visualize the interaction between cultured human epithelial cells and different strains of the bacterium, including the natural strain and those lacking either FrhA or PBD. The results demonstrated a 68% reduction in interaction with FrhA mutants and a 50% reduction with PBD mutants compared to the non-mutant bacterium. This highlights the significant contribution of the PBD region to epithelial cell binding during infection. Additionally, experiments using these bacterial strains showed that, in the absence of PBD, V. cholerae could not colonize the intestines of mice or form biofilms, which are communities of bacteria adhering to living tissues.

Protein binding domain of FrhA is also found in Antarctic bacteria

One of the most noteworthy findings of this research is the discovery of functional parallels between V. cholerae and the Antarctic bacterium M. primoryensis. Similar to V. cholerae, M. primoryensis also possesses a FrhA protein containing a PBD region, sharing a remarkable 76% sequence similarity with its counterpart in V. cholerae. However, in the Antarctic bacterium, PBD serves to simultaneously bind aquatic microorganisms such as diatoms and ice, facilitating the formation of mixed-species microcolonies on Antarctic ice to optimize photosynthesis and nutrient acquisition. Intriguingly, the authors observed that V. cholerae expressing PBD from M. primoryensis could not only bind to epithelial cells and infect the gastrointestinal tracts of mice but also bind to diatoms similarly to the polar bacterium.

The presence of PBD is unique to V. cholerae within the Vibrio genus and is also found in closely related Vibrio metoecus and Vibrio vulnificus, as well as in bacteria outside the Vibrionales order, such as M. primoryensis, Aeromonas, and Shewanella species. This limited distribution of PBD within Vibrionales and its occurrence in these distant bacteria suggests horizontal gene transfer: V. cholerae, a natural marine inhabitant, acquired the diatom-binding PBD from another bacterium associated with diatoms, possibly even from M. primoryensis.

Original article:

Lloyd CJ, et al. Proc Natl Acad Sci USA 2023;120(39):e2308238120