The Pneumococcus, Prominent Microbiologists, Contributions and Cross-Connections

‘He who knows syphilis knows medicine’ goes the saying. In a similar way this adage could be applied to the Pneumococcus, aka Streptococcus pneumoniae, Diplococcus pneumoniae or Diplococcus lanceolatus by saying “He who knows S. pneumoniae knows microbiology”.

Many ‘big names’ studied the organism.  Their work on the Pneumococcus led to scientific discoveries in serotyping, vaccine development, and contributed much to our understanding of genetics and pathogen resistance. While some names are little known today, a few still permeate the pneumococcal literature as eponyms.PNEUMOCOCCUS copy

William Osler called the Pneumococcus the ‘captain on the ship of death’ referring to the high mortality of the organism in the pre-antibiotic era. Indeed, mortality from pneumococcal pneumonia in the preantibiotic era was 30-50%.

The Quellung reaction named after Friedrich (“Fred”) Neufeld is still a recognized way to identify S. pneumoniae in tissue sections. ‘Quellung’ is the German word for ‘swelling’ as the polysaccharide capsule becomes visibly larger upon exposure to antiserum. Neufeld also discovered bile solubility of the Pneumococcus, and, most importantly, the principle of opsonization, the facilitation of phagocytosis by WBC in the presence of serum factors.

Anton Weichselbaum from Vienna was one of the first to recognize the broad pathogenic potential of S. pneumoniae. He reported meningitis, bacteremia and endocarditis cases and named the organism Diplococcus pneumoniae. He also discovered the ‘other diplococcus’, Neisseria meningitidis.

In a landmark study, Oswald Avery showed convincingly that DNA carried the information which determines morphologic changes. His experiments with rough and smooth variants of S. pneumoniae laid the foundation for genetic manipulation via transformation.

Robert Austrian’s life-long work on serotyping led to the polyvalent vaccines still in use today. With antibiotic resistance on the rise, there is now renewed interest in preventative measures which were nearly abandoned when penicillins and sulfonamides were discovered.

One should not omit Sir Almroth Wright from the list of giants that contributed to the field. His steadfast support of immunization efforts for the coal miners of South Africa saved many lives.

Louis Pasteur and George Sternberg are credited with the initial isolation of the Pneumococcus in 1881. Sternberg, according to Robert Koch the “father of American microbiology” worked with Walter Reed on many projects including tuberculosis. Note: the Reed-Sternberg giant cell in Hodgkins lymphoma were named so in honor of 2 other researchers, Dorothy Reed and Carl (von) Sternberg. Confusingly, they associated these cells with a special form of lymphatic TB. The latter worked in Vienna like Weichselbaum.

Work by the Klemperers showed that immunization with killed bacteria conferred protection which can be passively transferred, thus laying the foundation of the concept of humoral immunity.

Morganroth found already in 1911 that optochin, a quinine derivative, had antipneumococcal activity. The drug proved too toxic for clinical use but was the first attempt at chemotherapy, predating Ehrlich’s Salvarsan by more than 10 years.

The Pneumococcus continues to be a threat and remains a focus of research. The pneumococcal vaccines available are preventing infection with the serotypes they contain but efficacy is an age-related phenomenon. In the elderly, protection is rather incomplete. Antibiotic resistance to penicillins has steadily increased in the last 30 years. We rely on the activity of vancomycin for cases of meningitis but tolerance to vancomycin has been described in 1999, including isolates from the CSF. Fortunately, true vancomycin resistance seems to be still rare.

General References:

R Austrian JID 1999;179(Suppl 2):S338
E Janoff  Streptococcus pneumoniae.  Chapter 201 Mandell, PPID 2014
D Watson. CID 1993;17: 913
L Mitchell.  Concise Rev Pediatr Infect Dis.2001, p531

 

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