Difficult to Stomach: H. pylori and Gastric Cancer

It is well known to most of us that bacteria cause some of the deadliest infectious diseases in humans and animals but did you know that bacteria can also cause cancer?  This is true in the case of Helicobacter pylori, a Gram negative spiral shaped bacteria which colonizes the mucus layer that covers the inner human stomach tissues. The interesting and unique feature of this bacteria is their ability to survive in the acidic environment of the stomach.

H. pylori secrete urease, an enzyme that breaks down urea into ammonia which neutralizes the acidic pH in stomach, allowing the bacteria to survive in this harsh environment [1] H. pylori is a common bacterium found in humans and according to the Center for Disease Control (CDC) about two-thirds of the world’s population harbors H. pylori. Most individuals infected with H. pylori do not present any symptoms or have serious illness, but in some individuals H. pylori causes peptic ulcer disease. Moreover, now it is estimated that H. pylori accounts for majority of the stomach and upper small intestine ulcers in humans [1 – 2].

How does H. pylori relate to Cancer? Cancer is a group of diseases that is characterized by abnormal cell growth and invade and spread to different part of the system. Gastric cancer is the 4th most common type of cancer and traditionally was not known to be related to infectious microorganisms. This perception changed in 1982, when two Australian scientists Barry Marshall and Robin Warren reported the presence of H. pylori in a patient with chronic gastritis and gastric and duodenal ulcers [3]. Further research provided compelling evidence linking H. pylori infections to the development stomach cancer. In 1994, H. pylori was officially classified as cancer causing agent or carcinogen by the International Agency for Research on Cancer (IARC) – World Health Organization (WHO) [4]. Now it is widely accepted that H. pylori infection can contribute to the development of gastric cancer and of gastric mucosa-associated lymphoid tissue (MALT) lymphoma [5]. But it should be noted that infection with H. pylori alone does not lead to stomach cancer; other factors such as the genetic susceptibility, are also necessary and important for the development of stomach cancer.

H. pylori is very difficult bacteria to grow and is microaerophilic, meaning it grows in environments with lower levels of oxygen than are present in the atmosphere. The bacterium is also facultatively intracellular inside the human host, meaning it can reproduce inside and outside of human cells, making it difficult to treat with antibiotics. There is a huge interest in studying H. pylori among scientists and the pharmaceutical industry because of the rapid emergence of drug resistance to currently available proton pump inhibitor with antibiotics, e.g. Clarithromycin and Amoxicillin[6]. The only method approved by the U.S. Food and Drug Administration (FDA) to test the antimicrobial susceptibility of H. pylori is by performing an Agar MIC following the Clinical Laboratory Standard Institute (CLSI) guidelines. At Emery Pharma, we are supporting drug discovery companies in evaluating the antimicrobial property of their test articles against H. pylori using CLSI/FDA approved microbiological techniques. We maintain more than 100 well-characterized clinical isolates of H. pylori in our strain collections. Many of these isolates are confirmed to be highly resistant to current standard antibiotics such as Metronidazole and Clarithromycin. If you want to evaluate the antimicrobial activity of your lead candidates against H. pylori, please contact us at info@emerypharma.com.

About the authors

Kavitha Srinivasa holds a Ph.D. in Microbiology and is currently working as Research Intern with Emery Pharma.

Sridhar Arumugam holds a Ph.D. degree in Microbiology and he is the Director of Cell and Microbiology with Emery Pharma.

References

  1. Sostres, C., Carrera-Lasfuentes, P., Benito, R., Roncales, P., Arruebo, M., Arroyo, M.T., Bujanda, L., García-Rodríguez, L.A. and Lanas, A., 2015. Peptic ulcer bleeding risk. The role of Helicobacter pylori infection in NSAID/low-dose aspirin users. The American journal of gastroenterology, 110(5), pp.684-689.
  2. Plummer, M., Franceschi, S., Vignat, J., Forman, D. and de Martel, C., 2015. Global burden of gastric cancer attributable to Helicobacter pylori. International journal of cancer, 136(2), pp.487-490.
  3. Marshall, B. and Warren, J.R., 1984. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. The Lancet, 323(8390), pp.1311-1315.
  4. Anonymous Live flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Lyon, 7–14 June 1994. IARC Monogr. Eval. Carcinog. Risks Hum. 1994; 61:1–241
  5. Rugge, Massimo, Matteo Fassan, and David Y. Graham. “Epidemiology of gastric cancer.” In Gastric Cancer, pp. 23-34. Springer International Publishing, 2015.
  6. Shiota, S., Reddy, R., Alsarraj, A., El-Serag, H.B. and Graham, D.Y., 2015. Antibiotic resistance of Helicobacter pylori among male United States veterans. Clinical Gastroenterology and Hepatology, 13(9), pp.1616-1624.