Question

• Describe the pathogenesis (properties) of the microbes that cause shigellosis, typhoid fever, cholera, gastroenteritis, stomach ulcers

Answer 1

ANSWER

PATHOGENCITY

(a) Shigellosis

• Shigellae cause bacillary dysentery.Infection occurs by ingestion. The minimun infective dose is low,as few as 10-100 bacilli are capable of initiating the disease,probably because they survive gastric acidity better than other enterobacteria.
• Bacterimia may occur in severe infections,particularly in malnourished children and in AIDS
• Though Sh dysenteriae Type 1 forms an exotoxin, it appears to be much less important in pathogensis than the ability of the bacillus to penetrateand multiply in colonic mucosa.
• Nontoxigenic mutants can still cause dysentry but not noninvasive ones.
• HeLa or Hep -2 cells or by the Congo red binding test is used to demonstrate the invasive property of the bacillus

Direct Invasion of Epithelial Cells

In the large intestine, it invades using transcytosis and transports through basolateral epithelium using M cells which are mainly responsible for immune activation of intestinal lymphoid tissue by antigen recognition. Following transcytosis, it induces macrophages and cellular apoptosis. This results in the release of inflammatory cytokines such as IL-1 and IL-18 which results in intestinal inflammation and subsequent activation of the innate immune system. Shigella is released from the macrophages after following apoptosis and inflammation. It continues to invade the adjacent epithelium and the immune system by using the intercellular actin polymerization process. As Shigella invades the epithelial cells, it activates nuclear factor (kappa B) in the cells causing the production of IL-8 which stimulates recruitment of neutrophils at the site causing more inflammation and epithelial damage. It causes impaired absorption of nutrients causing diarrhea.

Toxin production

Another mechanism for cell injury by Shigella is through the production of enterotoxin 1 and 2 which plays a part in impaired fluid and nutrient absorption causing Shigella-associated diarrhea. Cytotoxin Shigella dysenteriae serotype 1 is responsible for cytotoxicity and vascular lesions in the colon and other organs such as kidneys causing bloody diarrhea and complications such as hemolytic uremic syndrome (HUS).

(b) Typhoid fever

Typhoid fever, also known as enteric fever, is a potentially fatal multisystemic illness caused primarily by Salmonella enterica serotype typhi and, to a lesser extent, S enterica serotypes paratyphi A, B, and C. The terms typhoid and enteric fever are commonly used to describe both major serotypes.

Typhoid fever has a wide variety of presentations that range from an overwhelming multisystemic illness to relatively minor cases of diarrhea with low-grade fever. The classic presentation is fever, malaise, diffuse abdominal pain, and constipation

Typhoid fever is transmitted by ingestion of food or water contaminated with the typhoid bacillus. This route of infection is shared with nontyphoidal Salmonella serovars (NTS), the causative agents of gastroenteritis. However, the diseases caused by these two distinct groups of bacteria are very different from a clinical perspective. While gastroenteritis caused by NTS is characterised by a rapid onset after a short incubation period (12-72h) and a brief duration (<10 days), typhoid fever has a considerably longer incubation period (median of 5 to 9 days) and longer duration of symptoms (fever persists for approximately three weeks). Also, gastroenteritis is an infection that remains localized to the intestine and mesenteric lymph nodes in immunocompetent patients, while typhoid fever is a systemic infection during which S. Typhi colonizes the liver, spleen and bone marrow in addition to the intestine and the mesenteric lymph nodes . The short clinical course of gastroenteritis suggests that the onset of an adaptive immune response results in clearance of the infection. On the contrary, S. Typhi can persist in human tissue for long periodsof time, indicating that the organism has a greater propensity to evade immune responses than nontyphoidal Salmonella serovars.

The pathogenesis of enteric fever depends on a number of factors including the infecting species and infectious dose. Ingested organisms survive exposure to gastric acid before gaining access to the small bowel, where they penetrate the epithelium, enter the lymphoid tissue, and disseminate via the lymphatic or hematogenous route.

(c) Cholera

A better understanding of the source of infection is very much necessary for the management and effective prophylaxis of any diseases. In the case of cholera, contaminated water and feces of persons infected with V. cholerae are the primary sources of infection. Planktons and zooplankton harboring the infectious agent and certain environmental factors such as surface change and terrestrial nutrient discharge are also among the factors that indirectly lead to the production of more hosts .

The mechanism of invasion begins as soon as the bacterium establishes itself in the bowel, following the colonization of the epithelial layer of the small intestine by penetrating the mucous. The penetration of the mucous is facilitated by mucolytic enzymes which help to destroy the mucous integrity, and also the long tail of the invading organism allows it to propel itself through the thick mucosal layer. The attachment Vibrio onto the microvilli of the small intestine is aided by the so-called pili on the bacterium which is one of the major factors which attributes to the darting motility . The production of an endotoxin by the bacteria, called CT, is the major key for the virulence mechanism. So it is proved that only toxigenic strains of Vibrio, i.e., Vibrio that produces CT, are capable of causing cholera.

The CT that is made is comprised of six protein subunits: one A subunit and five copies of B subunits, generally denoted as AB5. B subunit is also known as the binding factor which binds to the GM1 ganglioside receptor of the epithelial cells of the small intestine. Once bound with the target cells, it forms a toxin complex which is then endocytosed by the cell. As soon as the process of endocytosis takes place, the enzymatic activation of A subunit occurs leading to increased adenylate cyclase activity, thereby increasing the concentration of cAMP to more than 120-folds. This in turns leads to increased permeability of the chloride channels subsequently mediating the efflux of more ATP-mediated chloride ions and secretion of mere H2O, Na+, K+ and HCO3− into the lumen of the intestine . The increased absorption of water as well as electrolytes is responsible for the massive dehydration leading to the clinical symptoms of cholera.

(d) gastroenteritis

The word "gastroenteritis" originates from the Greek word gastron, meaning "stomach," and enteron, meaning "small intestine." So the word "gastroenteritis" means "inflammation of the stomach and small intestine." Medically, gastroenteritis is defined as a diarrheal disease, in other words, an increase in bowel movement frequency with or without vomiting, fever, and abdominal pain.

Causes of gastroenteritis include bacterial, viral, fungal, and parasitic, but this article will focus on bacterial causes. Causes of infectious diarrhea vary among different geographical regions, urban to rural areas, and depend on co-morbidities and host immune status. Other than norovirus, important causes of watery diarrhea include Clostridium perfringens, and enterotoxigenic Escherichia coli (ETEC). Bacterial causes are more responsible for severe cases of infectious diarrhea than other infectious etiologies.

The gut bacteria cause diarrhea by different mechanisms including adherence, mucosal invasion, and toxin production. Knowledge of pathophysiology and the mechanism of these pathogenic strategies also help in the evaluation and management of the disease. One of the main functions of the small intestine is to absorb fluids. With the disorder of the small intestine, the fluid does not get absorbed properly, and the action of different toxins causes the intestinal lining to start excreting fluid which results in relatively loose or watery stools.

Inoculum size is one of the important virulence factors that cause pathology. For Shigella and enterohemorrhagic Escherichia coli (EHEC), at a minimum of 10–100 bacteria can cause infection, while one hundred thousand or one million of Vibrio cholerae bacteria are required to cause infection. For this reason, infective doses of different pathogens differ in a great range and depend on the host as well as bacteria.

Adherence is another virulence factor for enteric pathogens. Some bacteria need to adhere themselves to the mucosal lining of the gastrointestinal tract initially. They produce various adhesins and other cell-surface proteins which help them to attach to intestinal cells. V. cholerae, for example, adheres to the brush border of small-intestinal enterocytes via specific surface adhesins, including the toxin-coregulated pilus and other accessory colonization factors. Enterotoxigenic E. coli, which causes watery diarrhea, produces an adherence protein called colonization factor antigen. This is necessary for colonization of the upper small intestine by the organism before the production of enterotoxin, causing disease.

Both cytotoxin production and bacterial invasion and destruction of intestinal mucosal cells can cause dysentery. Shigella and enteroinvasive E. coli infections are characterized by the organisms’ invasion of mucosal epithelial cells, intraepithelial multiplication, and subsequent spread to adjacent cells.

Toxin production is another important virulence factor. These toxins include enterotoxins, which cause watery diarrhea by acting directly on secretory mechanisms in the intestinal mucosa, and cytotoxins, which destroy mucosal cells and associated inflammatory diarrhea.

(e) stomach ulcers

Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1) Survival in the acidic stomach; (2) movement toward epithelium cells by flagella-mediated motility; (3) attachment to host cells by adhesins/receptors interaction; (4) causing tissue damage by toxin release.

After entering the host stomach, H. pylori utilizes its urease activity to neutralize the hostile acidic condition at the beginning of infection. Flagella-mediated motility is then required for H. pylori to move toward host gastric epithelium cells, followed by specific interactions between bacterial adhesins with host cell receptors, which thus leads to successful colonization and persistent infection. Finally, H. pylori releases several effector proteins/toxins, including cytotoxin-associated gene A (CagA), and vacuolating cytotoxin A (VacA), causing host tissue damage. In addition, the gastric epithelium layer, which forms the major interface between H. pylori and the host, secretes chemokines to initiate innate immunity and activate neutrophils, and further lead to the formation of clinical diseases such as gastritis and ulcer. In summary, four steps are critical for H. pylori colonization and pathogenesis: (1) Survival under acidic stomach conditions; (2) movement toward epithelium cells through flagella-mediated motility; (3) attaching to host receptors by adhesins; (4) causing tissue damage by toxin release