Quellung reaction

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The quellung reaction, also called the Neufeld reaction, is a biochemical reaction in which antibodies bind to the bacterial capsule of Streptococcus pneumoniae , Klebsiella pneumoniae , Neisseria meningitidis , Bacillus anthracis , Haemophilus influenzae , [1] Escherichia coli , and Salmonella . The antibody reaction allows these species to be visualized under a microscope. If the reaction is positive, the capsule becomes opaque and appears to enlarge.

Photomicrograph of Streptococcus pneumoniae bacteria revealing capsular swelling using the Neufeld quellung test. Notice the two streptococci at the top of the photo that appear to have no capsule. Pneumococcus CDC PHIL 2113.jpg
Photomicrograph of Streptococcus pneumoniae bacteria revealing capsular swelling using the Neufeld quellung test. Notice the two streptococci at the top of the photo that appear to have no capsule.

Quellung is the German word for "swelling" and describes the microscopic appearance of pneumococcal or other bacterial capsules after their polysaccharide antigen has combined with a specific antibody. The antibody usually comes from serum taken from an immunized laboratory animal. As a result of this combination, and precipitation of the large, complex molecule formed, the capsule appears to swell, because of increased surface tension, and its outlines become clearly demarcated.

The pneumococcal quellung reaction was first described in 1902 by the scientist Fred Neufeld, and applied only to Streptococcus pneumoniae, both as microscopic capsular swelling and macroscopic agglutination (clumping visible with the naked eye). [2] It was initially an intellectual curiosity more than anything else, and could distinguish only the three pneumococcal serotypes known at that time. However, it acquired an important practical use with the advent of serum therapy to treat certain types of pneumococcal pneumonia in the 1920s because selection of the proper antiserum to treat an individual patient required correct identification of the infecting pneumococcal serotype, and the quellung reaction was the only method available to do this. Dr. Albert Sabin made modifications to Neufeld's technique so that it could be done more rapidly, [3] and other scientists expanded the technique to identify 29 additional serotypes. [4]

Application of Neufeld’s discoveries to other important areas of research came when Fred Griffith showed that pneumococci could transfer information to transform one serotype into another. [5] Oswald Avery, Colin MacLeod, and Maclyn McCarty later showed that the transforming factor was deoxyribonucleic acid, or DNA. [6]

Serum therapy for infectious diseases was displaced by antibiotics in the 1940s, but identification of specific serotypes remained important as the understanding of the epidemiology of pneumococcal infections still required their identification to determine where different serotypes spread, as well as the variable invasiveness of different serotypes. Understanding the prevalence of various serotypes was also critical to the development of pneumococcal vaccines to prevent invasive infections.

The quellung reaction has been used to identify the 93 known capsular serotypes of Streptococcus pneumoniae in diagnostic settings, but in recent years it has been challenged by the latex agglutination method, and further by molecular typing techniques such as the polymerase chain reaction, which detect DNA and therefore target genetic differences between serotypes. [7] Currently, there are 100 known capsular serotypes. [8]

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<i>Streptococcus</i> Genus of bacteria

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<span class="mw-page-title-main">Oswald Avery</span> Canadian-American physician

Oswald Theodore Avery Jr. was a Canadian-American physician and medical researcher. The major part of his career was spent at the Rockefeller Hospital in New York City. Avery was one of the first molecular biologists and a pioneer in immunochemistry, but he is best known for the experiment that isolated DNA as the material of which genes and chromosomes are made.

<span class="mw-page-title-main">Frederick Griffith</span> British bacteriologist

Frederick Griffith (1877–1941) was a British bacteriologist whose focus was the epidemiology and pathology of bacterial pneumonia. In January 1928 he reported what is now known as Griffith's Experiment, the first widely accepted demonstrations of bacterial transformation, whereby a bacterium distinctly changes its form and function.

<i>Streptococcus pneumoniae</i> Species of bacterium

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The Avery–MacLeod–McCarty experiment was an experimental demonstration, reported in 1944 by Oswald Avery, Colin MacLeod, and Maclyn McCarty, that DNA is the substance that causes bacterial transformation, in an era when it had been widely believed that it was proteins that served the function of carrying genetic information. It was the culmination of research in the 1930s and early 20th century at the Rockefeller Institute for Medical Research to purify and characterize the "transforming principle" responsible for the transformation phenomenon first described in Griffith's experiment of 1928: killed Streptococcus pneumoniae of the virulent strain type III-S, when injected along with living but non-virulent type II-R pneumococci, resulted in a deadly infection of type III-S pneumococci. In their paper "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III", published in the February 1944 issue of the Journal of Experimental Medicine, Avery and his colleagues suggest that DNA, rather than protein as widely believed at the time, may be the hereditary material of bacteria, and could be analogous to genes and/or viruses in higher organisms.

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Fred (Friedrich) Neufeld was a physician and bacteriologist who discovered the pneumococcal types. This discovery led Fred Griffith to show that one pneumococcal type could be transformed into another. Subsequently, Oswald Avery demonstrated that the transforming substance was DNA. All modern molecular biology has evolved from this work.

Austrian syndrome, also known as Osler's triad, is a medical condition that was named after Robert Austrian in 1957. The presentation of the condition consists of pneumonia, endocarditis, and meningitis, all caused by Streptococcus pneumoniae. It is associated with alcoholism due to hyposplenism and can be seen in males between the ages of 40–60 years old. Robert Austrian was not the first one to describe the condition, but Richard Heschl or William Osler were not able to link the signs to the bacteria because microbiology was not yet developed.

<span class="mw-page-title-main">Anne Wyllie</span> New Zealand microbiologist and epidemiologist

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<span class="mw-page-title-main">Daniela M. Ferreira</span> Brazilian immunologist

Daniela M. Ferreira is a Brazilian British immunologist. She is a specialist in bacterial infection, respiratory co-infection, mucosal immunology and vaccine responses. She is currently Professor of Respiratory Infection and Vaccinology at the Oxford Vaccine Group in the Department of Paediatrics at the University of Oxford and the Director of the Liverpool Vaccine Group at the Liverpool School of Tropical Medicine. She leads a team of scientists studying protective immune responses against pneumococcus and other respiratory pathogens such as SARS-CoV2. Her team has established a novel method of inducing pneumococcal carriage in human volunteers. They use this model to:

References

  1. Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. (2007). Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated Reviews Series). Hagerstwon, MD: Lippincott Williams & Wilkins. p. 340. ISBN   978-0-7817-8215-9.
  2. Neufeld, F. (1902). "Ueber die Agglutination der Pneumokokken und uber die Theorien der Agglutination". Zeitschrift für Hygiene und Infektionskrankheiten. 40: 54–72. doi:10.1007/bf02140530. S2CID   1143320.
  3. Sabin, Albert B. (May 20, 1933). "Immediate Pneumococcus Typing Directly from Sputum by the Neufeld Reaction". Journal of the American Medical Association. 100 (20): 1584–1586. doi:10.1001/jama.1933.02740200018004.
  4. Beckler, Edith; MacLeod, Patricia (November 1934). "The Neufeld Method of Pneumococcus Type Determination as Carried Out in a Public Health Laboratory: A Study of 760 Typings". Journal of Clinical Investigation. 13 (6): 901–907. doi:10.1172/jci100634. PMC   436037 . PMID   16694257.
  5. Griffith, Fred (January 1928). "The Significance of Pneumococcal Types". Journal of Hygiene. 27 (2): 113–159. doi:10.1017/s0022172400031879. PMC   2167760 . PMID   20474956.
  6. Avery, Oswald T.; MacLeod, Colin M.; McCarty, Maclyn (February 1, 1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types - Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". Journal of Experimental Medicine. 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMC   2135445 . PMID   19871359.
  7. PCR Deduction of Pneumococcal Serotypes Archived September 4, 2009, at the Wayback Machine . Center for Disease Control. Retrieved October 22, 2010.
  8. "GPS :: Global Pneumococcal Sequencing Project". www.pneumogen.net. Retrieved 2021-10-09.

Further reading