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Decoding cholera: How a comma-shaped bacterium creates an epidemic

P Surat

Vibrio cholerae, as seen under light microscope (Right, By CDC [Public domain]), or by transmission electron microscope (Left, By Tom Kirn, Ron Taylor, Louisa Howard - Dartmouth Electron Microscope Facility[Public domain]), via Wikimedia Commons
Vibrio cholerae, as seen under light microscope (Right, By CDC [Public domain]), or by transmission electron microscope (Left, By Tom Kirn, Ron Taylor, Louisa Howard - Dartmouth Electron Microscope Facility[Public domain]), via Wikimedia Commons  

In April 2018, three people in Odisha died from cholera after drinking “pana”- a ritualistic drink that was made from pond water of the village. In India, around eight lakh cholera cases were reported between 2004 to 2008 due to contaminated water.

In a recent study, researchers led by Chandradipa Ghose from Vidyasagar University, West Bengal, found that Vibrio cholerae, the cholera-causing bacterium, communicates with other bacteria in its vicinity and uses flagella, a whip-like structure, to survive and attach to surfaces in water bodies. This increases its survival potential, leading to the emergence of epidemics.

Vibrio cholerae thrives in aquatic habitats. One of the ways by which it survives is forming biofilms on biotic or abiotic surfaces. Biofilms consist of microbial communities embedded in an extensive matrix of exopolysaccharides (EPS). Cholera bacteria use quorum sensing, a cell-cell communication method where a cell can gauge the density of cells around it, to form biofilms. In this mode of communication, bacteria release a signalling molecule which is then sensed by their neighbours. When the concentration of this signalling molecule is high, the bacteria assume high cell density in their vicinity and secrete EPS, leading to the formation of biofilms.

To determine the role of this communication in the spread of cholera, the researchers mutated the genes which synthesise autoinducer – the quorum sensing signalling molecule – in the bacterial strain that caused a cholera epidemic in Kolkata in 1992. There are two types of autoinducers in Vibrio – autoinducer 1, which is involved in communicating with fellow Vibrio bacteria, and autoinducer 2, which communicates with other bacterial species. The researchers found that bacteria which could not synthesise either or both of these signalling molecules secreted higher EPS matrix, had wrinkled cell surfaces (as opposed to smooth), and produced more biofilms. All of these traits contribute to increasing the cholera bacteria’s persistence in variable surroundings.

Vibrio is a highly motile bacterium with a single flagellum on one end. The flagellum not only propels the bacteria, but also doubles as a sensory organ to explore the surfaces around it. The researchers found that removing the flagellum by deleting the gene which creates it also generated similar effects as mutating the quorum sensing signalling molecules - higher EPS matrix expression, wrinkled surface, and greater biofilm production. “This alternate mechanism was observed in a group of Vibrio cholerae that are highly toxigenic and virulent,” states Ghose.

The researchers found that for these two players in cholera pathogenesis - flagella and quorum sensing - one signalling pathway becomes predominant in the absence of the other. The increase in EPS in the absence of autoinducers is brought about by the flagella, while the increase in EPS in the absence of flagella is dependent on autoinducers.

How does this system work in real life?

When Vibrio numbers are low in a local aquatic ecosystem, the concentration of secreted autoinducer molecules in the water is also less. This leads to a flagella-dependent increase in EPS production, wrinkled surface, and biofilm generation, establishing a stable Vibrio population. “EPS signalling provides adaptive features for the pathogen to survive in different environments by inducing rapid biofilm forming ability,” says T Ramamurthy, scientist at Translational Health Science and Technology Institute, who was not involved in the study. Interestingly, wrinkled cells with excess EPS also show increased expression of toxins which contribute to the diarrhoea and dehydration associated with cholera.

“This study establishes an alternate biofilm signalling mechanism that comes into action by the interaction of quorum sensing autoinducers with flagellar structure,” says Ghosh. The presence of biofilm protects the bacteria from changes in its environment and EPS makes it more potent – potentially triggering a cholera epidemic.

Written By

Surat completed her PhD in life sciences from Tata Institute of Fundamental Research (TIFR), Mumbai in Jan 2016. She is currently working as a freelance science writer and editor.