Overload

Vibrio cholerae infection

Category: Illness or disabilities

Type

Involuntary

Introduction and description

 

Vibrio cholerae is a Gram-negative, comma-shaped bacterium that causes the disease cholera

Not all strains cause the disease, some strains of V. cholerae are not pathogenic. Two serogroups of V. cholerae, O1 and O139, are the cause -  O1 causes the majority of outbreaks, while O139 – first identified in Bangladesh in 1992 – is confined to Southeast Asia.

In recent years, infections with the classical biotype of V. cholerae O1 have become rare and are limited to parts of Bangladesh and India. However, new variant strains have been detected in several parts of Asia and Africa. Observations suggest these strains cause more severe cholera with higher case fatality rates.

Many other serogroups of V. cholerae, can cause a cholera-like illness. Only toxigenic strains of serogroups O1 and O139 have caused widespread epidemics.

The final pandemic of cholera originating in 1961 in Indonesia, was marked by the emergence of a new strain, nicknamed El Tor, which still persists today in developing countries.

Description

 

The bacterium's natural habitat is brackish or saltwater and to enable it to get about it has a flagellum at one cell pole as well as pili.

A flagellum is a lash-like appendage that protrudes from the cell body. [The word flagellum in Latin means whip]. The primary role of the flagellum is locomotion, but it also often has function as a sensory organelle, being sensitive to chemicals and temperatures outside the cell.  A pilus (Latin for 'hair'; plural : pili) is a hair like appendage found on the surface of many bacteria.

V. cholerae is a facultative anaerobe, a facultative anaerobe is an organism that can use oxygen but also has anaerobic methods of energy production. So it can survive with or without oxygen.

Bacteriophage

 

 A bacteriophage  is a virus that infects and replicates within a bacterium. The term is derived from "bacteria" and the Greek: φαγεῖν (phagein), "to devour".

The word devour is misleading.  Generally speaking, the viruses do not actually harm their host, but co-exist, using them like a Trojan horse to enter other organisms.  In effect the bacteria, perhaps being one less likely to be attacked by the immune system because it is one naturally found in the host, is used as a hiding place in the host – a place in which the virus can breed and spread its little phages.

V. cholerae has its own permanent bacteriophage, a temperate bacteriophage is inserted into the V. cholerae genome.  In virology, temperate refers to the ability of some bacteriophages to display a lysogenic life cycle.  In the lysogenic cycle, the phage DNA first integrates into the bacterial chromosome to produce the prophage. When the bacterium reproduces, the prophage is also copied and is present in each of the daughter cells.  In other words, each time the bacteria produces babies, so does the phage.

Toxins

Vibrio cholerae has two key toxins which belong to the phage :

  • the toxin co-regulated pilus (TCP), a colonization factor, and
  • cholera toxin, an exotoxin.

The toxin genes are contained within the genome of an integrated filamentous phage identified in 1996. In the past few years, it has been shown that this relies on novel processes for phage DNA integration, replication and secretion.

The genetic island that encodes TCP has also been described as a filamentous phage; however, these sequences are unlike the genome of any previously characterized filamentous phage. PMID: 12615217

Colonization of the small intestine requires the toxin coregulated pilus (TCP), a thin, flexible, filamentous appendage on the surface of bacterial cells.

Infectious phage particles are produced when V. cholerae infects humans. Phage particles are secreted from bacterial cells without lysis, that is there is no breakdown of the membrane of a cell.  There are eight genes involved in phage reproduction, packaging, secretion, integration, and regulation.

To put this more simply, it is the phage that is the pathogen.  It is like a sort of parasite on its bacterial host and some of the bacterial strains have been infected, some have not. 

Life cycle

 

When consumed, most of the bacteria do not survive the acidic conditions of the human stomach. The few surviving bacteria conserve their energy and stored nutrients during the passage through the stomach by shutting down much protein production.

When the surviving bacteria exit the stomach and reach the small intestine, they propel themselves through the thick mucus that lines the small intestine using their flagellum to reach the intestinal walls where they can attach and thrive.  Once the cholera bacteria reach the intestinal wall they no longer need the flagella to move. The bacteria stop producing the protein flagellin to conserve energy and nutrients by changing the mix of proteins which they express in response to the changed chemical surroundings. On reaching the intestinal wall, V. cholerae start producing the toxic proteins.

Vibrio cholerae thus secretes the toxin described above during colonization of the epithelium in the small intestine: 12 h post-inoculation, bacteria detach from the epithelial surface and move into the fluid-filled lumen - the cavities or channels within the tubular structures. Designated the "mucosal escape response," this phenomenon requires RpoS, a gene encoding a Sigma factor that regulates transcription in the bacteria.  In this safe haven they multiply. 

 

In other words, if they are not flushed away by the diarrhoea they can enter the blood stream and start colonising the body.  This is why there is coma and death.  It is not the dehydration, but the entry of the bacteria with its toxins and phages – armed and ready to go – into the body as a whole.  Why should the bacteria [or perhaps more correctly the phages]  be so keen to kill its host?  The watery body is actually an ideal host for this organism and I don’t suppose it cares whether we are alive or dead.  Its aim is not to kill, it is to reproduce.

Molecular epidemiological surveillance has revealed …a continual emergence of new epidemic clones. … it appears that the continual emergence of new toxigenic strains and their selective enrichment during cholera outbreaks constitute an essential component of the natural ecosystem for the evolution of epidemic V. cholerae strains and genetic elements that mediate the transfer of virulence genes. The ecosystem comprising V. cholerae, …the aquatic environment, and the mammalian host offers an understanding of the complex relationship between pathogenesis and the natural selection of a pathogen.  PMID:  9841673

Vibrio cholerae as a more general pathogen

It is our hypothesis that this bacteria, and the strains that are armed with toxins and the bacteriophage, may be responsible for far more disease and illness than just cholera. 

Cholera kills if the bacteria gets into the blood stream and is allowed to proliferate or get to the brain, but even where the immune system fights back, it may still represent a threat at some later stage.  And it may not be the actual bacteria that is the problem but the phages.  By using antiobiotics, for example, we may be killing the bacteria, releasing the phages and also damaging the bacteria in the intestines that are capable of controlling the bacteria.

For example

A 77-year-old man presented to our hospital with a clinical scenario suspicious for endocarditis with septic emboli to the lungs and splenic abscess. Vibrio cholerae was isolated from purulent material aspirated from the abscess. Medical therapy and percutaneous drainage of the abscess were unsuccessful. The patient underwent splenectomy and distal pancreatectomy revealing a pancreatic tail carcinoma involving the spleen and colon. The patient later expired secondary to metastatic disease. This case represents the first isolation of V. cholerae from a splenic abscess but also illustrates that although newer imaging technologies have made the diagnosis of splenic abscess easier, the true etiology of the abscess may remain elusive.

PMID:  12151192

and

From January 1974 to May 2015, a total of 48 patients with non-O1, non-O139 Vibrio cholerae bacteremia with skin and soft tissue infections were reported. Males predominated. Liver cirrhosis, chronic liver disease and alcohol abuse were common comorbidities. The soft tissue lesions most commonly described were localised cellulitis, with or without bullous and haemorrhagic lesions (66.7%), while necrotising fasciitis was more rare (29.2%). Of the 48 patients with non-O1, non-O139 V. cholerae bacteremic skin and soft tissue infections, 20 (41.7%) died despite treatment.  PMID:  26503346

The role of Intestinal flora

The healthy human intestine is colonized by as many as 1014 bacteria belonging to more than 500 different species forming a microbial ecosystem of unsurpassed diversity, termed the microbiota. The microbiota's various bacterial members engage in a physiological network of cooperation and competition within several layers of complexity. Within the last 10 years, technological progress in the field of next-generation sequencing technologies has tremendously advanced our understanding of the wide variety of physiological and pathological processes that are influenced by the commensal microbiota PMID: 26185088

A rather fascinating relationship has been found between V. cholerae and a type of bacteria that lives in the intestine called Blautia obeum -  a species of gram-positive bacteria. B. obeum is an anaerobe.  It has been shown that B. obeum along with other relevant taxa play an important role both in the recovery process from V. cholerae infection and microbiota maturation in children. Moreover, experiments in model mice show that B. obeum strain AI-2 reduces the pathogenicity of V. cholerae. The data show that the expression of quorum sensing autoinducers by B. obeum is increased in V. cholera infections and they repress the expression of several V. cholera virulence factors. 

In other words as long as we do not mess up our intestinal flora using antibiotics, we have the cure for Cholera and protection against the bacteria within us.

Related observations