Information

How does Vibrio cholerae benefit from infecting its host?


As far as I know, V. cholerae secretes a toxin called choleragen into the intestinal lumen which affects the intestinal epithelial cells causing release of Na+ and Cl- ions into the lumen and reducing the lumen's water potential which causes water to flow into the intestinal lumen resulting in diarrhea. How does this benefit V. cholera in any way?


After V.cholerae gets into the human intestine it starts to multiply its numbers, and then becomes virulent after sufficiently expanding its numbers. This virulence drives the diarrhea which in part causes the bacteria to slough off into the intestinal lumen, and then into the external environment again.

So in short it uses the human intestine to increase cell numbers.

See work by Bonnie Bassler for a really fascinating understanding of the complexity of this infection.


VIBRIO | Vibrio Cholerae

F.Y.K. Wong , P.M. Desmarchelier , in Encyclopedia of Food Microbiology , 1999

Introduction

Vibrio cholerae is the aetiological agent of cholera, an epidemic disease of significant public health importance owing to its rapid spread in areas with poor sanitation and hygiene, and its severe consequences when access to health care is limited. A vibrio-like organism was first described as the cholera pathogen as early as 1854, although the V. cholerae bacillus was not successfully isolated until 30 years later. The modern history of cholera is characterized by seven recorded pandemics, during which V. cholerae spread globally in a series of disease upsurges. Cholera associated with the current seventh pandemic is endemic over much of Asia, Africa, and Latin America. In spite of improved public health controls in some of these regions, the disease remains a major public health menace. The emergence of novel epidemic strains has led to new disease upsurges, and greater challenges for cholera management and control.


Vibrio Cholerae

Cholera is an infection in the small intestine caused by the bacterium Vibrio cholerae. The primary symptoms of cholera are profuse, painless diarrhea and vomiting of clear fluid. These symptoms usually start suddenly, one to five days after ingestion of the bacteria. The diarrhea is frequently described as &ldquorice water&rdquo in nature and may have a fishy odor. If the severe diarrhea is not treated with intravenous rehydration, it can result in life-threatening dehydration and electrolyte imbalances.

Figure: Adult cholera patient: A person with severe dehydration due to cholera &ndash note the sunken eyes and decreased skin turgor which produces wrinkled hands.


Initial Stages of Colonization

Relying on and then relinquishing protection

V. cholerae has a complex acid tolerance response involving numerous factors such as the ToxR-regulated porin, OmpU, the transcriptional regulators CadC and HepA, the gluthatione synthetase GshB, and the DNA repair and recombination enzyme RecO, among others [7–9]. To date, the roles of OmpU and CadC have been corroborated by in-frame deletions [8,10]. Free-living V. cholerae cells are very sensitive to the low pH of the stomach, and the dose required to cause infection in healthy volunteers, 10 11 cells, is perhaps unrealistically high [11]. However, when the pH of the stomach is buffered, the number of cells required to cause the symptoms of the disease can be reduced by several orders of magnitude, between 10 4 –10 6 cells (Fig 1A) [11,12]. Furthermore, in endemic regions, some cholera patients have been found to have low gastric acid production, indicating that these individuals might be more susceptible to free-living V. cholerae than others [13–15]. With further respect to the physiological state of the bacteria, V. cholerae might also enter the human host in a dormant state called viable but nonculturable (VBNC) [16–19]. VBNC cells in other species have been shown to have increased acid tolerance [20]. V. cholerae VBNC cells were given to human volunteers, and these cells were able to effectively colonize the SI and were shed as culturable free-living cells [18].

V. cholerae might also be ingested as microcolonies or in a hyperinfectious state [21–23]. Once shed after intestinal colonization, V. cholerae cells can be found in a hyperinfectious state that is thought to lower the infectious dose required to colonize secondary individuals [21]. Furthermore, after infection, subpopulations of V. cholerae keep expressing the gene encoding TcpA, a major component of the toxin-coregulated pilus (TCP), an essential intestinal colonization factor [22,23]. Microcolonies are TCP-mediated clusters of V. cholerae cells that confer numerous properties to the bacterium (See section “Final Stages of Colonization”). It is possible that microcolonies shed from cholera patients might confer resistance to the low pH of the stomach to V. cholerae. However, to our knowledge, the role of microcolonies in low pH tolerance and how the bacterium relinquishes them upon arrival in the SI remain to be determined (Fig 1A).

Biofilms are bacterial communities that collectively produce a protective exopolysaccharide matrix, which facilitates survival during stress-inducing environmental changes such as low pH or the presence of antimicrobials [24]. V. cholerae that are ingested as part of a biofilm can successfully survive the low pH of the human stomach [25]. Cells within a biofilm may reach the stomach either attached to a substrate or as conditionally viable environmental cells (CVEC)—clumps of dormant cells embedded in a biofilm matrix that can be recovered using enriched culturing techniques (Fig 1A) [25]. Furthermore, while forming biofilm, V. cholerae can be found in a hyperinfectious physiological state [26]. The infectious dose for biofilm-derived V. cholerae is orders of magnitude lower than that of planktonic cells regardless of whether the biofilm is intact or dispersed [26]. The relationship between bile and biofilm remains contested [27,28]. Hung and Mekalanos showed that bile stimulates biofilm formation in V. cholerae as biofilms increase the resistance of the bacterium to bile acids [27]. Conversely, it was recently found that taurocholate, a component of bile, induces the degradation of V. cholerae biofilms [28]. The authors suggested that contact with bile components upon reaching the intestinal lumen might allow for the dispersal of the bacterium in the early stages of colonization (Fig 1A) [28]. Once in the lumen, the bacterium must withstand the presence of antimicrobial agents. It has been shown that OmpU protects against bile acids [29] and antimicrobial peptides [30] among others.

Overall, it is possible that in the early stages of cholera epidemics, V. cholerae might be primarily ingested attached to surfaces while forming biofilms, such as the chitinaceous shell of copepods, as CVEC or as VBNC [4,5,31–34]. However, once the cholera epidemic begins, the bacterium might be predominantly consumed as part of microcolonies shed by other cholera patients or in a hyperinfectious state [21].


Concluding Remarks

V. cholerae non-O1 as well as O1 and O139 inhabit highly diverse fish species. In most cases it seems that the bacteria cause the fish no harm on the contrary, V. cholerae may be a part of the normal flora of at least some of the fish species, like tilapia and carp. Fish might have a mutualistic relationship with V. cholerae. The fish provide food and shelter for this bacterium while the bacterium may assist the fish to digest its food (e.g., chitin and protein). From an epidemiological point of view, the fish carry the cholera bacteria from one place to another. So eventually, if waterbirds feed on the fish, V. cholerae may be transferred in some waterbird species' digestive tracts and thus be globally spread.


Secret to how cholera adapts to temperature revealed

This image shows a smooth colony of Vibrio cholerae (left) next to a rough colony formed at 37C (right). Credit: Santos et al. CC BY 4.0

Scientists have discovered an essential protein in cholera-causing bacteria that allows them to adapt to changes in temperature, according to a study published today in eLife.

The protein, BipA, is conserved across bacterial species, which suggests it could hold the key to how other types of bacteria change their biology and growth to survive at suboptimal temperatures.

Vibrio cholerae (V. cholerae) is the bacteria responsible for the severe diarrhoeal disease cholera. As with other species, V. cholerae forms biofilms—communities of bacteria enclosed in a structure made up of sugars and proteins—to protect against predators and stress conditions. V. cholerae forms these biofilms both in their aquatic environment and in the human intestine. There is evidence to suggest that biofilm formation is crucial to V. cholerae's ability to colonize in the intestine and might enhance its infectivity.

"V. cholerae experiences a wide range of temperatures, and adapting to them is not only important for survival in the environment but also for the infection process," explains lead author Teresa del Peso Santos, a postdoctoral researcher at the Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Sweden. "We know that at 37 degrees Celsius, V. cholerae grows as rough colonies that form a biofilm. However, at lower temperatures these colonies are completely smooth. We wanted to understand how it does this."

The researchers screened the microbes for genes known to be linked with biofilm formation. They found a marked increase in the expression of biofilm-related genes in colonies grown at 37C compared with 22C.

To find out how these biofilm genes are controlled at lower temperatures, they generated random mutations in V. cholerae and then identified which mutants developed rough instead of smooth colonies at 22C. They then isolated the colonies to determine which genes are essential for switching off biofilm genes at low temperatures.

The most common gene they found is associated with a protein called BipA. As anticipated, when they intentionally deleted BipA from V. cholerae, the resulting microbes formed rough colonies typical of biofilms rather than smooth colonies. This confirmed BipA's role in controlling biofilm formation at lower temperatures.

To explore how BipA achieves this, the researchers compared the proteins produced by normal V. cholerae with those produced by microbes lacking BipA, at 22 and 37 degrees Celsius. They found that BipA alters the levels of more than 300 proteins in V. cholerae grown at suboptimal temperatures, increasing the levels of 250 proteins including virtually all known biofilm-related proteins. They also showed that at 37 degrees Celsius, BipA adopts a conformation that may make it more likely to be degraded. In BipA's absence, the production of key biofilm regulatory proteins increases, leading to the expression of genes responsible for biofilm formation.

These results provide new insights into how V. cholerae adapts to temperature and will help understand—and ideally prevent—its survival in different environments and transmission into humans.

"We have shown that BipA is critical for temperature-dependent changes in the production of biofilm components and alters colony shape in some V. cholerae strains," concludes senior author Felipe Cava, Associate Professor at the Department of Molecular Biology, and MIMS Group Leader and Wallenberg Academy Fellow, Umeå University. "Future research will address the effect of temperature- and BipA-dependent regulation on V. cholerae during host infection and the consequences for cholera transmission and outbreaks."


Introduction

Cholera continues to be a major cause of morbidity and mortality in many parts of the world [1]. It is contracted through ingestion of contaminated food or water and is characterized by profuse diarrhea and vomiting. Cholera toxin, the primary determinant of this clinical syndrome, is an AB5-type exotoxin composed of an A subunit non-covalently bound to five B subunits, arranged in a rosette to form a lectin recognizing the GM1 ganglioside [2]. The mechanism by which cholera toxin enters intestinal epithelial cells and disrupts function has been studied extensively in cultured cells [3–7]. Prior to entry into the cell, the A subunit is proteolytically cleaved into a catalytic A1 subunit and an A2 subunit, whose role is to maintain the non-covalent association to the B subunit GM1 lectin. This lectin forms an association with GM1 gangliosides that are concentrated in lipid rafts within the cell membrane. Once bound to GM1, retrograde transport on lipid rafts delivers cholera toxin to the endoplasmic reticulum. The A1 subunit then dissociates from the toxin complex and exits the endoplasmic reticulum to ADP-ribosylate the stimulatory G protein subunit, G. The modified G constitutively activates adenylyl cyclase, and levels of cAMP in intestinal epithelial cells rise. The consequent secretory diarrhea depends on opening of cAMP-responsive Cl − channels and flow of Cl − and water through the apical surface of the epithelial cell into the intestinal lumen. KCNN4, an intermediate conductance Ca 2+ -activated K + channel of mammals, maintains K + export through the basolateral aspect of the intestinal epithelial cell. Clotrimazole, which blocks the KCNN4 channel, has been shown to decrease cholera toxin-induced Cl − secretion in both cultured mammalian cells and mice [8,9]. These results suggest that simultaneous basolateral export of K + is required to maintain passage of Cl − through basolateral K + /Cl − cotransporters and apical Cl − channels into the intestinal lumen.

The utility of Drosophila melanogaster as a model host for human pathogens is well-established [10–18]. In the natural environment, Vibrio cholerae is closely associated with arthropods [19–21], and many have suggested that insects serve as vectors [22–26] or reservoirs [27–29] of V. cholerae. Thus, we hypothesized that insects or related arthropods might serve as excellent model hosts of V. cholerae. To test this, we subjected the model insect D. melanogaster to oral V. cholerae infection. Here we demonstrate that V. cholerae infection of D. melanogaster exhibits the following parallels to human disease: (i) ingestion of V. cholerae produces an intestinally-localized, lethal infection in the fly that is dependent on cholera toxin (ii) host susceptibility is dependent on Gsα, adenylyl cyclase, and the Drosophila KCNN4 channel homolog and (iii) clotrimazole, an inhibitor of the human KCNN4 channel, protects the fly against infection. However, we have also found differences between V. cholerae infection of mammals and flies. Ingestion of cholera toxin alone is sufficient to cause severe secretory diarrhea in humans and model mammals [30–33]. In contrast, in the fly, we have found that ingestion of cholera toxin is lethal only when pathogenic isolates of V. cholerae are ingested in tandem. Our findings not only demonstrate the utility of the fly as a model host for V. cholerae infection, but also suggest that the V. cholerae genome contains virulence factors specifically required for infection of non-mammalian hosts such as the fly.


Vibrio cholerae

Cholera is a diarrheal disease, easily mistakable for several others however, there are some clinical features that are characteristic and can help make the diagnosis.

The presence of watery diarrhea with the appearance of rice wash is characteristic. This is even more impressive when associated with acute severe dehydration.

Other symptoms may include:

Tenesmus and later cramps

Mental status alteration, from alert to restless, somnolent and even comatose

Signs associated with dehydration:

How did the patient develop cholera? What was the primary source from which the infection spread?

Cholera causes large epidemics, and pandemics around the globe. A local outbreak can quickly convert to an epidemic.

The life cycle of Vibrio cholerae allows the bacterium to live for years in an aquatic environment, its natural reservoir, where it survives adherent to crustaceans, algae and zooplankton.

Under the appropriate environmental conditions, V.Cholerae will multiply and reinitiate the free life cycle. However, if the environment is adverse, this pathogen is capable of maintaining a latent state, inactive, unidentifiable by culture and resistant to chlorine.

The infectious cycle of this bacillus occurs when the bacteria moves from its aquatic environment into a human through contaminated water and contaminated food.

Infected humans excrete bacteria contaminating a new environment and new water sources. Usually those who are infected excrete high numbers of bacteria, creating massive environmental contamination and rapid transmission to other humans.

In July 2012, a cholera outbreak began in Cuba, despite the fact that cholera was thought to have been eradicated in this country. As recently as October 2012, new cases were reported. In the same year, the epidemic in Haiti and the Dominican Republic continued.

According to the World Health Organization’s epidemiological report, the number of cholera cases during 2011 was 589,854, with a fatality rate of 1.3%. This number is the total number of cases reported in 58 countries however, 61% of this number corresponds to the outbreak affecting Haiti and the Dominican Republic since October 2010.

Another large percentage of the total of cases during 2011 came from the African continent, where the lethality rates are higher than in Haiti and Dominican Republic (Africa 2.22%, Dominican Republic 1.61% and Haiti 0.84%). We know that the real number of cases reported is much higher, due to underreporting and limitations of the surveillance systems.

The last great pandemic worldwide occurred in Latin America the first cases were reported in Peru in 1991. Peru was also the most affected country, with more than 300,000 cases reported during the first year. Until now the origins of this epidemic have been controversial, and the most supported theory is the one of multiple entry places along the coast of Peru due to contamination of water and food in large coastal cities.

New outbreaks keep emerging, even in areas where no case of cholera has ever been reported, which highlights the need of new measures to prevent and control great pandemics. Despite the existence of surveillance systems, water and food sanity, still no effective control to prevent appearance of new outbreaks has been achieved, mainly because such factors cannot be adequately regulated in developing countries.

What laboratory studies should you order and what should you expect to find?

Results that confirm the diagnosis

Isolation of the bacteria with a stool culture:

The culture medium most commonly used is thiosulfate citrate bile salts sucrose agar and taurocholate and tellurite gelatin agar

The serogroup can be identified using antiserum

Rapid direct exam with dark field microscopy allows a quick identification:

The bacillus can be observed easily with dark field microscopy

A characteristic high number of bacteria and chaotic movement is seen

A rapid dipstick test (Crystal VC) is now available and has sensitivity comparable to other methods but has relatively poor specificity. It may be suitable for use in the field as it has good negative predictive value.

What imaging studies will be helpful in making or excluding the diagnosis of cholera?

Imaging is not of benefit.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has cholera, what therapies should you initiate immediately?

Rehydration

Hypovolemia can result in lactic acidosis, shock and renal failure. Rehydration is the cornerstone of therapy:

Oral hydration is often effective when initiated early in the disease. Hypo-osmolar solutions have proven to be most effective at replacing volume and reducing the volume of diarrhea.

The WHO oral solution contains 2.6g sodium chloride, 2.9g trisodium citrate, 1.5g of potassium chloride and 13.5g glucose.

Oral hydration containing rice or cereal as the calorie source rather than glucose is more effective at reducing the volume and duration of diarrhea.

Rehydration volumes of 2200 to 4400mL are recommended for those over 30kg in weight.

Intravenous rehydration is recommended for those who have lost over 10% of their body weight, or are unable to take oral fluids because of vomiting or a depressed mental status.

An isotonic intravenous solution is recommended. Alternatives include:

Ringers lactate + 5% dextrose

Cholera or Dhaka solution (high glucose content)

Anti-infective agents

Antibiotics are an adjunct therapy and are generally initiated after the patient has been hydrated.

Antibiotic treatment shortens the duration of diarrhea and reduces the infectiousness of the stool. V.cholerae excretion is usually eliminated after 24 hours of antibiotic treatment

Oral antibiotics are generally recommended:

Doxycyline 300 mg as a single dose is as effective as multiple doses of oral tetracycline 500 mg given every 6 hours.

Fluoroquinolones are highly effective in areas where tetracycline resistance is prevalent.

Ciprofloxacin 1000 mg as a single dose was shown to be more effective than single dose doxycyline

Norfloxacin 400 mg daily x 3 days was shown to be more effective than single dose doxycyline

Macrolides have also proved to be effective in treating cholera

Erythromycin -12.5 mg/kg every six hours for three days

Azithromycin – 1gm single oral dose

How can cholera be prevented?

Vaccines

Among the prevention measures for this disease are sanitary education and water decontamination however these measures have been sometimes impossible to achieve in many countries. That is why a need for cholera vaccines continues.

As with every vaccine, an ideal balance between a rapid but lasting immunological response, with minimal side effects and easy access are integral. Despite the efforts, achieving this balance has not been easy, several vaccines have been developed during the last 20 years, not all being successful. Efforts to develop and patent successful vaccines are now progressing rapidly.

We know that the ideal vaccine for cholera should be administrated orally. The WC BS vaccine (Whole Cell B Subunit) was promising with short-term positive results however, in a long-term analysis it proved to be protective in only 50% of patients:

Even less protection in children and adults with blood group O

Less protection against biotype El Tor

Later, live attenuated vaccines, such as Vaxchora showed improved results during the 90’s:

Three oral vaccines against cholera are now available:

V. cholerae killed cell vaccine with recombinant B toxin (Dukoral, Crucell). Dukoral has a license in more than 60 countries and has been prequalified by WHO by the UN acquisition to be used in crisis areas for refugees in Indonesia, Sudan, Uganda and Mozambique.

The other vaccine type is available under two different brand labels. The vaccine consists of killed V. cholerae without the recombinant toxin: a) Shanchol, Shantha Biotechnics

Vaxchora is available as a single dose oral formulation of lyophilized live V cholerae CVD 103-HgR to be administered at least 10 days prior to potential exposure to cholera.

The first two vaccines are given in a 2-dose regimen (with the exception of Dukoral that requires 3 doses for children under 6 years old. There is increasing evidence that one dose may be sufficient in some areas.

A recent Cochrane review on oral vaccines against cholera concluded that whole cell inactivated vaccines can prevent 50-60% of cholera episodes during the first two years after the primary vaccine schedule. However, the authors recommend that the impact and cost effectiveness of incorporating these vaccines into the regular primary vaccine schedule in endemic countries should be restricted to areas where the prevalence and frequency of epidemics is high, and where there is limited access to basic sanitation and health services that provide quick treatment and rehydration.

The use of vaccine in Haiti has been debated by public health experts, now that the epidemic in this area has continued for more than 2 years. To date, a consensus about vaccine use has not been achieved. Nevertheless there is great interest in the development of a vaccine as a control measure for this disease.

WHO presently recommends use of vaccine during epidemics.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Seas, C, Gotuzzo, E, Mandel, GL, Bennett, JE, Dolin, R. “Vibrio cholerae”. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. 2000. pp. 2266-72.

“Cholera, diarrhea and dysentery update 2012, Cuba”.

“Cholera annual report 2011”. Wkly Epidemiol Rec. vol. 87. 2012. pp. 289-304.

Seas, C, Miranda, J, Gil, AI, Leon-Barua, R, Patz, J, Huq, A. “New insights on the emergence of cholera in Latin America during 1991: the Peruvian experience”. The American journal of tropical medicine and hygiene. vol. 62. 2000. pp. 513-7.

Seas, C, Gotuzzo, E, Rakel, R, Bope, E. “The infectious Diseases – Cholera”. Conn’s Current Therapy. 2009.

Seas, C, Gotuzzo, E, Yu, V, Weber, R. “Vibrio cholerae (Cholera)”. Antimicrobial Therapy and Vaccines. 2003.

Waldor, MK, Hotez, PJ, Clemens, JD. “A national cholera vaccine stockpile–a new humanitarian and diplomatic resource”. The New England journal of medicine. vol. 363. 2010. pp. 2279-82.

Sur, D, Kanungo, S, Sah, B, Manna, B, Ali, M, Paisley, AM. “Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial”. PLoS Negl Trop Dis. vol. 5. 2011. pp. e1289

Sinclair, D, Abba, K, Zaman, K, Qadri, F, Graves, PM, Anh, DD. “Oral vaccines for preventing cholera – Use of oral cholera vaccines in an outbreak in Vietnam: a case control study”. Cochrane Database Syst Rev. vol. 5. 2011. pp. CD008603

Ryan, ET. “Haiti in the context of the current global cholera pandemic”. Emerg Infect Dis. vol. 17. 2011. pp. 2175-6.

Clemens, JD. “Vaccines in the time of cholera”. Proceedings of the National Academy of Sciences of the United States of America. vol. 108. 2011. pp. 8529-30.

Shin, S, Desai, SN, Sah, BK, Clemens, JD, Chao, DL, Halloran, ME. “Oral vaccines against cholera – Vaccination strategies for epidemic cholera in Haiti with implications for the developing world”. Clin Infect Dis. vol. 52. 2011. pp. 1343-9.

“Outbreak of cholera in Cuba, potential risk for European travellers”. 12 July 2012.

Ley, B, Khatib, AM, Thriemer, K, von Seidlein, L, Deen, J, Mukhopadyay, A. “Evaluation of a rapid dipstick (Crystal VC) for the diagnosis of cholera in Zanzibar and a comparison with previous studies”. PLoS One.. vol. 7. 2012. pp. e36930

Qadri, Firdausi, Wierzba, Thomas F., Ali, Mohammad, Chowdhury, Fahima, Khan, Ashraful I., Saha, Amit. “Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh”. N Engl J Med. vol. 374. 2016. pp. 1723-1732.

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Secret to how cholera adapts to temperature revealed

Scientists have discovered an essential protein in cholera-causing bacteria that allows them to adapt to changes in temperature, according to a study published today in eLife.

The protein, BipA, is conserved across bacterial species, which suggests it could hold the key to how other types of bacteria change their biology and growth to survive at suboptimal temperatures.

Vibrio cholerae (V. cholerae) is the bacteria responsible for the severe diarrhoeal disease cholera. As with other species, V. cholerae forms biofilms - communities of bacteria enclosed in a structure made up of sugars and proteins - to protect against predators and stress conditions. V. cholerae forms these biofilms both in their aquatic environment and in the human intestine. There is evidence to suggest that biofilm formation is crucial to V. cholerae's ability to colonise in the intestine and might enhance its infectivity.

"V. cholerae experiences a wide range of temperatures, and adapting to them is not only important for survival in the environment but also for the infection process," explains lead author Teresa del Peso Santos, a postdoctoral researcher at the Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Sweden. "We know that at 37 degrees Celsius, V. cholerae grows as rough colonies that form a biofilm. However, at lower temperatures these colonies are completely smooth. We wanted to understand how it does this."

The researchers screened the microbes for genes known to be linked with biofilm formation. They found a marked increase in the expression of biofilm-related genes in colonies grown at 37C compared with 22C.

To find out how these biofilm genes are controlled at lower temperatures, they generated random mutations in V. cholerae and then identified which mutants developed rough instead of smooth colonies at 22C. They then isolated the colonies to determine which genes are essential for switching off biofilm genes at low temperatures.

The most common gene they found is associated with a protein called BipA. As anticipated, when they intentionally deleted BipA from V. cholerae, the resulting microbes formed rough colonies typical of biofilms rather than smooth colonies. This confirmed BipA's role in controlling biofilm formation at lower temperatures.

To explore how BipA achieves this, the researchers compared the proteins produced by normal V. cholerae with those produced by microbes lacking BipA, at 22 and 37 degrees Celsius. They found that BipA alters the levels of more than 300 proteins in V. cholerae grown at suboptimal temperatures, increasing the levels of 250 proteins including virtually all known biofilm-related proteins. They also showed that at 37 degrees Celsius, BipA adopts a conformation that may make it more likely to be degraded. In BipA's absence, the production of key biofilm regulatory proteins increases, leading to the expression of genes responsible for biofilm formation.

These results provide new insights into how V. cholerae adapts to temperature and will help understand - and ideally prevent - its survival in different environments and transmission into humans.

"We have shown that BipA is critical for temperature-dependent changes in the production of biofilm components and alters colony shape in some V. cholerae strains," concludes senior author Felipe Cava, Associate Professor at the Department of Molecular Biology, and MIMS Group Leader and Wallenberg Academy Fellow, Umeå University. "Future research will address the effect of temperature- and BipA-dependent regulation on V. cholerae during host infection and the consequences for cholera transmission and outbreaks."

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Cholera - Vibrio cholerae infection

Cholera, caused by the bacteria Vibrio cholerae, is rare in the United States and other industrialized nations. Cholera can be life-threatening but it is easily prevented and treated. Travelers, public health, medical professionals, and outbreak responders should be aware of areas with high rates of cholera, know how the disease spreads, and what to do to prevent it.

Find answers to frequently asked questions about Cholera.

Cholera infection is often mild or without symptoms, but can sometimes be severe and life-threatening.

If you live in or are visiting an area where cholera is occurring or has occurred, follow the five basic prevention steps.

Cholera patients should be evaluated and treated quickly. With proper treatment, even severely ill patients can be saved.


General Information

Below you will find answers to commonly asked questions about cholera.

What is cholera?

Cholera is an acute, diarrheal illness caused by infection of the intestine with the toxigenic bacterium Vibrio cholerae serogroup O1 or O139. An estimated 2.9 million cases and 95,000 deaths occur each year around the world. The infection is often mild or without symptoms, but can be severe. Approximately 1 in 10 people who get sick with cholera will develop severe symptoms such as watery diarrhea, vomiting, and leg cramps. In these people, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours.

Where is cholera found?

The cholera bacterium is usually found in water or in foods that have been contaminated by feces (poop) from a person infected with cholera bacteria. Cholera is most likely to occur and spread in places with inadequate water treatment, poor sanitation, and inadequate hygiene.

Cholera bacteria can also live in the environment in brackish rivers and coastal waters. Shellfish eaten raw have been a source of infection. Rarely, people in the U.S. have contracted cholera after eating raw or undercooked shellfish from the Gulf of Mexico.

How does a person get cholera?

A person can get cholera by drinking water or eating food contaminated with cholera bacteria. In an epidemic, the source of the contamination is usually the feces of an infected person that contaminates water or food. The disease can spread rapidly in areas with inadequate treatment of sewage and drinking water. The infection is not likely to spread directly from one person to another therefore, casual contact with an infected person is not a risk factor for becoming ill.

What are the symptoms of cholera?

Cholera infection is often mild or without symptoms, but can be severe. Approximately 1 in 10 people who get sick with cholera will develop severe symptoms such as watery diarrhea, vomiting, and leg cramps. In these people, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours.

How long after infection do the symptoms appear?

It usually takes 2-3 days for symptoms to appear after a person ingests cholera bacteria, but the time can range from a few hours to 5 days.

Who is most likely to get cholera?

Persons living in places with unsafe drinking water, poor sanitation, and inadequate hygiene are at the highest risk for cholera.

What should I do if I or someone I know gets sick?

If you think you or a member of your family might have cholera, seek medical attention immediately. Dehydration can be rapid so fluid replacement is essential. If you have oral rehydration solution (ORS), start taking it immediately it can save a life. Continue to drink ORS at home and while traveling to get medical treatment. If an infant has watery diarrhea, continue breastfeeding.

How is cholera diagnosed?

To test for cholera, doctors must take a stool sample or a rectal swab and send it to a laboratory to look for the cholera bacteria.

What is the treatment for cholera?

Cholera can be simply and successfully treated by immediate replacement of the fluid and salts lost through diarrhea. Patients can be treated with oral rehydration solution (ORS), a prepackaged mixture of sugar and salts that is mixed with 1 liter of water and drunk in large amounts. This solution is used throughout the world to treat diarrhea. Severe cases also require intravenous fluid replacement. With prompt appropriate rehydration, fewer than 1% of cholera patients die.

Antibiotics shorten the course and diminish the severity of the illness, but they are not as important as rehydration. Persons who develop severe diarrhea and vomiting in countries where cholera occurs should seek medical attention promptly.

Should I be worried about getting cholera from others?

The disease is not likely to spread directly from one person to another therefore, casual contact with an infected person is not a risk factor for becoming ill.

How can I avoid getting sick with cholera?

Be aware of whether cholera cases have recently occurred in an area you plan to visit. However, the risk for cholera is very low for people visiting areas with epidemic cholera when simple prevention steps are taken.

All visitors or residents in areas where cholera is occurring or has occurred should follow recommendations to prevent getting sick: