The life and behaviour of the infectious agent are often at the centre of scientific research on infectious disease. Currently, the structure and cycle of SARS-CoV2, the covid-19 virus, is being studied by a host of scientists attempting to locate possible sites of interference and manipulation. To study this, we must capture the agent.
In Medical Museion we hold a unique object from 1853, which incapsulates the watery excrement from a cholera patient. Since 1853, scientists have uncovered much knowledge on the cycle and effect of Vibrio cholerae – or, the cholera bacterium. And even though we do not (yet?) know how to control all it’s outbreaks, we know in intimate details its life cycle and its effects in the human body. In the following, human biologist Kristine Frøsig Moseholm tells us about the life of Vibrio cholerae.
The Vibrio cholerae
The cholera bacterium is a free-living organism that primarily lives in brackish water. Once ingested and inside the human body, most cholera bacteria do not survive the acidic conditions of the human stomach. The few bacteria that survive, however, enter the small intestines. From here a number of events unfold in the body and in the bacterium. The expression of virulence genes (i.e. genes that produce destructive effects in the host) are activated by bile salts secreted from the gallbladder, as well as molecules from the first immune response against this foreign intruder. The bacterium uses its flagella or “tail” to propel itself through the thick mucus lining the intestinal wall. It secretes molecules that kill the existing microbiota and expresses a hair-like structure, the pilus, which it uses to attach itself to the intestinal wall, forming microcolonies. From here, it starts to colonise larger parts of the small intestines by dividing rapidly. The bacteria secrete cholera toxin which penetrates the intestinal surface and disrupts transport mechanisms of the gut wall. As a result, large amounts of salts are secreted from the cells into the intestines, causing massive water efflux. The large amount of water in the intestines makes the body to vomit and have diarrhea. The body tries to control the bacterial infection through an immune response. Immune cells infiltrate the gut mucosa and secrete molecules killing the foreign intruder. Now multiplied by many, the cholera bacteria initiate an “escape response”: Virulence genes are repressed, and the bacteria detach from the intestinal wall. A set of survival genes, helping to evade the immune response, are expressed as the bacteria are flushed through the body and out with the diarrhea rice water stools. In the first hours after escaping the body through diarrhea, Cholerae vibrio is in a hyper-infectious state and ready for transmission to another host. Thereafter, the bacteria down-regulate expression of virulence genes that make them cause disease and up-regulate expression of genes important for long term survival. Now, it is no longer strongly infectious, but merely stay quietly alive. In the aquatic environment the bacteria form biofilm (metaphorically described as “microbe cities”) with other bacteria on the shells of crustaceans.
Cholera in the body
The journey has severe consequences for the host or patient body: Massive fluid loss from severe diarrhea and vomiting results in dehydration and imbalance in the salts in the body. The body responds by holding back all fluids. Urine output decreases, the mouth becomes dry, the skin wrinkles on hands and feet. Blood pressure drops and all blood vessels in the surface of the skin are constricted in the attempt to keep the blood to the vital organs and to increase blood flow in the central veins. This makes the patient turn cold and the skin takes on a bluish colour. The body tries to compensate by secreting adrenaline, resulting in increased heart rate to increase output of oxygenated blood out into the body, however, often unsuccessfully. The poor blood perfusion of tissue leads to metabolic acidosis: the inability to meet the cells oxygen demand, leads the cells to shift to anaerobic metabolism, resulting in increased secretion of the by-product lactic acid, which lowers pH in the tissue and blood. Because of the acidosis, the patients breathing will start to be deep, laboured and gasping to increase the exhalation of carbon dioxide in an attempt to reduce acidity. Due to the electrolyte imbalance, the muscles will feel weak and might start cramping, and the patient will have altered consciousness and might go into coma. Without treatment the body goes into shock. The blood pressure and cardiac output drops resulting in further decrease in the blood flow in tissue and organs. The cells respond to lack of oxygen and the high acidity with panic. Inflammatory and toxic molecules are released, damaging surrounding tissue. The body is no longer fighting an infection, it is fighting itself. An irreversible damaging cascade is initiated, and the complex system of the body starts to breakdown. In the end, systemic damage and multiple organ failure results in death due to cardiorespiratory failure.
The story of the Vibrio cholerae is based on a longer version of the text published in Plethora Magazine vol. 10, December 2020. The magazine is displayed in the exhibition “Capturing Epidemics: Photographs by Nicolai Howalt”, showing at Medical Museion during the winter 2020/2021 (click here to read more about the exhibition).