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.
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]
Griffith's experiment, reported in 1928 by Frederick Griffith, was the first experiment suggesting that bacteria are capable of transferring genetic information through a process known as transformation. Griffith's findings were followed by research in the late 1930s and early 40s that isolated DNA as the material that communicated this genetic information.
Streptococcus is a genus of gram-positive coccus or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales, in the phylum Bacillota. Cell division in streptococci occurs along a single axis, so as they grow, they tend to form pairs or chains that may appear bent or twisted. This differs from staphylococci, which divide along multiple axes, thereby generating irregular, grape-like clusters of cells. Most streptococci are oxidase-negative and catalase-negative, and many are facultative anaerobes.
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.
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.
Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic member of the genus Streptococcus. They are usually found in pairs (diplococci) and do not form spores and are non motile. As a significant human pathogenic bacterium S. pneumoniae was recognized as a major cause of pneumonia in the late 19th century, and is the subject of many humoral immunity studies.
Pleural empyema is a collection of pus in the pleural cavity caused by microorganisms, usually bacteria. Often it happens in the context of a pneumonia, injury, or chest surgery. It is one of the various kinds of pleural effusion. There are three stages: exudative, when there is an increase in pleural fluid with or without the presence of pus; fibrinopurulent, when fibrous septa form localized pus pockets; and the final organizing stage, when there is scarring of the pleura membranes with possible inability of the lung to expand. Simple pleural effusions occur in up to 40% of bacterial pneumonias. They are usually small and resolve with appropriate antibiotic therapy. If however an empyema develops additional intervention is required.
Maclyn McCarty was an American geneticist, a research scientist described in 2005 as "the last surviving member of a Manhattan scientific team that overturned medical dogma in the 1940s and became the first to demonstrate that genes were made of DNA." He had worked at Rockefeller University "for more than 60 years." 1994 marked 50 years since this work's release.
The bacteria capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily washed off, and it can be the cause of various diseases.
Pneumococcal polysaccharide vaccine (PPSV)—known as Pneumovax 23 (PPV-23)—is the first pneumococcal vaccine derived from a capsular polysaccharide.
Pneumococcal pneumonia is a type of bacterial pneumonia that is caused by Streptococcus pneumoniae (pneumococcus). It is the most common bacterial pneumonia found in adults, the most common type of community-acquired pneumonia, and one of the common types of pneumococcal infection. The estimated number of Americans with pneumococcal pneumonia is 900,000 annually, with almost 400,000 cases hospitalized and fatalities accounting for 5-7% of these cases.
Pneumococcal conjugate vaccine is a pneumococcal vaccine and a conjugate vaccine used to protect infants, young children, and adults against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). It contains purified capsular polysaccharide of pneumococcal serotypes conjugated to a carrier protein to improve antibody response compared to the pneumococcal polysaccharide vaccine. The World Health Organization (WHO) recommends the use of the conjugate vaccine in routine immunizations given to children.
Pneumococcal vaccines are vaccines against the bacterium Streptococcus pneumoniae. Their use can prevent some cases of pneumonia, meningitis, and sepsis. There are two types of pneumococcal vaccines: conjugate vaccines and polysaccharide vaccines. They are given by injection either into a muscle or just under the skin.
Robert Austrian was an American infectious diseases physician and, along with Maxwell Finland, one of the two most important researchers into the biology of Streptococcus pneumoniae in the 20th century.
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.
A pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae, which is also called the pneumococcus. S. pneumoniae is a common member of the bacterial flora colonizing the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. However, it is also a cause of significant disease, being a leading cause of pneumonia, bacterial meningitis, and sepsis. The World Health Organization estimates that in 2005 pneumococcal infections were responsible for the death of 1.6 million children worldwide.
Pneumolysin is a virulence factor of the Gram-positive bacteria Streptococcus pneumoniae.
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.
Anne Louise Wyllie is a New Zealand microbiologist who was the lead author of a 2020 research article which led to the development of the SalivaDirect PCR method of testing saliva for SARS-CoV-2, the virus that causes COVID-19. She has also worked on community studies to better understand pneumococcal disease. She is a research scientist in epidemiology with the Public Health Modeling Unit at Yale University.
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: