scholarly journals THE TRANSFORMATION OF PNEUMOCOCCAL TYPES

1930 ◽  
Vol 51 (1) ◽  
pp. 99-122 ◽  
Author(s):  
Martin H. Dawson

R forms of Pneumococcus may be converted into S forms of the homologous Type. In addition to the methods previously reported,—(1) animal passage and (2) growth in anti-R sera,—conversion may be effected by the following procedures as employed by Griffith; (1) The subcutaneous injection, in white mice, of large amounts of living R organisms. (2) The subcutaneous injection, in white mice, of small amounts of living R organisms together with the heat-killed bacteria from large amounts of homologous S cultures. There are "varying degrees of constancy of the R variant"; but by these means it has been possible to effect conversion of all R forms selected. Attempts to cause a further "degradation" of R organisms by continued growth in homologous immune serum have been unsuccessful. Type II S and III S vaccines are equally effective in producing conversion when heated for 15' at 60°C., or for 15' at 100°C. Type I S vaccine, however, while effective in causing conversion when heated for 15' at 60°C., apparently loses this property when heated for 15' at 100°C. R vaccines, and vaccines of other organisms, when injected together with live R cultures, have always failed to produce conversion. The causes responsible for conversion under these experimental conditions are discussed and the possibility of the occurrence of a similar process under natural conditions in human beings is indicated.

1928 ◽  
Vol 48 (6) ◽  
pp. 791-804 ◽  
Author(s):  
William S. Tillett

1. Rabbits, vaccinated by repeated intravenous injections of suspensions of heat-killed R pneumococci, acquire a marked degree of active immunity to infection with the virulent S forms of Pneumococcus Types I and II. Previously (1) it was shown that the immunization of rabbits with R cells induces active resistance to Type III infection. This immunity is effective when the infecting organisms are injected either intravenously, intraperitoneally, or intradermally. 2. Whole citrated blood or serum of rabbits immunized with R pneumococci, under the experimental conditions described, is capable of passively protecting normal rabbits against Type I and Type III infection. Whole blood appears to be more effective than an equivalent amount of serum. 3. Passive protection of mice by the use of whole blood or serum of the immune rabbits has been entirely ineffectual. This is in striking contrast to the results obtained with type-specific immune serum. 4. This form of acquired resistance to pneumococcus infection, elicited by R organisms which are devoid of type specificity, and exemplified in animals whose sera possess no demonstrable type-specific antibodies, has many characteristics strongly suggesting that the underlying mechanism differs from that concerned in type-specific immunity.


1966 ◽  
Vol 64 (2) ◽  
pp. 129-175 ◽  
Author(s):  
Fred Griffith

1. In the course of the examination of sputum from cases of lobar pneumonia, observations have been made on the incidence of the chief types of pneumococci. In the district from which the material was obtained, there was an apparent local diminution in the number of cases of lobar pneumonia due to Type II; the figures were 32·6 per cent. of Type II cases in the period 1920–22, and only 7·4 per cent. in the period 1924–27. The incidence of Type I was approximately the same in the two periods, the percentages being 30·6 and 34·3.2. Several different serological varieties of pneumococci have been obtained from the sputum of each of several cases of pneumonia examined at various stages of the disease. This has occurred most frequently in cases of pneumonia due to Type I, and in two instances four different types of Group IV were found in addition to the chief types. The recovery of different types is facilitated by the inoculation of the sputum (preserved in the refrigerator), together with protective sera corresponding to the various types in the order of their appearance.3. Two interesting strains of Group IV pneumococci have been obtained from pneumonic sputum.One was an R strain which produced typical rough colonies, yet preserved its virulence for mice and its capacity to form soluble substance. This R pneumococcus developed a large capsule in the mice, which died of a chronic type of septicaemia. A strain producing smooth colonies was obtained from it in the course of a prolonged series of passage experiments.The second strain, which was proved not to be a mixture, agglutinated specifically with the sera of two different types. In the peritoneal cavity of the mouse the specific soluble substance of each type was produced.4. A method of producing the S to R change through ageing of colonies on chocolate blood medium containing horse serum is described. After two to three days' incubation small rough patches appear in the margins of the smooth colonies, and from these pure R strains can be isolated.5. It has been shown that the R change is not equally advanced in the descendants of virulent pneumococci which have been exposed to the action of homologous immune serum. Some R strains form traces of soluble substance in the peritoneal cavity of the mouse; these revert readily to the virulent S form and, in addition, are able to produce active immunity. Others show no evidence of S antigen; spontaneous reversion takes place with difficulty, if at all, and they are incapable of producing active immunity. The stronger the immune serum used, the more permanent and complete is the change to the R form.6. Restoration of virulence to an attenuated R strain, with recovery of the S form of colony and of the original serological type characters may be obtained by passage through mice. The change from the R to the S form is favoured by the inoculation of the R culture in large doses into the subcutaneous tissues; but the most certain method of procuring reversion is by the inoculation of the R culture, subcutaneously into a mouse, together with a large dose of virulent culture of the same type killed by heat.Incubation of such a mixture in vitro does not induce reversion.7. Reversion of an R strain to its S form may occasionally be brought about by the simultaneous inoculation of virulent culture of another type, especially when this has been heated for only a short period to 60° C., e.g. R Type II to its S form when inoculated with heated Type I culture.8. Type I antigen appears to be more sensitive to exposure to heat than Type II antigen, since the former loses the power to cause reversion when heated to 80° C, whereas Type II culture remains effective even after steaming at 100° C.9. The antigens of certain Group IV strains appear to be closely related to that of Type II, and are equally resistant to heat. Steamed cultures of these Group IV strains cause the R form derived from Type II to revert to its S form, while they fail to produce reversion of the R form derived from Type I.10. The inoculation into the subcutaneous tissues of mice of an attenuated R strain derived from one type, together with a large dose of virulent culture of another type killed by heating to 60° C., has resulted in the formation of a virulent S pneumococcus of the same type as that of the heated culture.The newly formed S strain may remain localised at the seat of inoculation, or it may disseminate and cause fatal septicaemia.The S form of Type I has been produced from the R form of Type II, and the R form of Type I has been transformed into the S form of Type II.The clear mucinous colonies of Type III have been derived both from the R form of Type I and from the R form of Type II, though they appear to be produced more readily from the latter. The newly formed strains of Type III have been of relatively low virulence, and have frequently remained localised at the subcutaneous seat of inoculation.Virulent strains of Types I and II have been obtained from an R strain of Group IV.11. Heated R cultures injected in large doses, together with small doses of living R culture have never caused transformation of type, and only rarely produced a reversion of the R form of Type II to its virulent S form.12. The results of the experiments on enhancement of virulence and on transformation of type are discussed and their significance in regard to questions of epidemiology is indicated.


1919 ◽  
Vol 30 (2) ◽  
pp. 123-146 ◽  
Author(s):  
Mildred C. Clough

In this paper are reported the results of a study of nine strains of pneumococci agglutinating with antipneumococcus sera of all three types (Nos. I, II, and III). Seven of the strains were the cause of serious or fatal infections in human beings. Morphologically they were typical pneumococci with characteristic growth on ordinary media. Most of the strains were soluble in bile, fermented inulin, and caused no precipitation on glucose ascitic fluid agar. Two of the strains, however, resembled streptococci in these three cultural characteristics, but have been regarded as pneumococci on account of their serological reactions. Variations in the cultural reactions occurred with several strains while they were under observation. The virulence of the strains varied greatly, some strains being almost non-pathogenic, and others killing mice in doses of 0.000001 cc. of a 24 hour broth culture. Antipneumococcus Sera I, II, and III agglutinated all the strains in fairly high dilution (1:8 to 1:64 or higher), while normal horse serum caused no agglutination. Antipneumococcus Sera I, II, and III stimulated active phagocytosis of all the strains, while no phagocytosis occurred in control preparations with normal horse serum. These strains elaborated a soluble substance in the body of inoculated mice which caused the formation of a precipitate when the peritoneal washings, cleared by centrifugalization, were added to the antipneumococcus sera of all three types. Antipneumococcus Sera I, II, and III protected mice equally well against 1,000 to 10,000 times the minimal lethal dose of the two strains with which protection tests could be carried out. Absorption of serum of Types I and II with the homologous pneumococcus removed the agglutinins and the bacteriotropins for all these strains. Absorption of these sera with Strains T and N removed the agglutinins and the bacteriotropins for the homologous strain only, and not for typical members of Type I or II, or for the other atypically agglutinable strains reported in this paper. The agglutinins concerned in the agglutination of these peculiar strains are therefore minor agglutinins. As shown not only by agglutination tests, but also by protection tests and agglutinin absorption tests, these organisms bear the same relation to Types I, II, and III, as do atypical Type II strains to Type II. Immune sera were prepared with these strains, and each strain was tested with all the immune sera by means of phagocytic and agglutinative reactions. In general, the strains were found to be serologically distinct, though some interrelationships existed between Strains V and R, and between Strains H, F, and N. These sera had no activity towards strains belonging to Type I or II, or atypical Type II. A mutation occurred in one of the strains, B, while it was under observation. On isolation this strain had the cultural reactions of a typical pneumococcus, and had the phagocytic and agglutinative reactions of an atypical Type II. After 6 months cultivation on blood agar its serological reactions changed, and it became actively phagocyted and agglutinated in antipneumococcus sera of Types I, II, and III. Its cultural characteristics also changed, and it became bile-insoluble, did not ferment inulin, and caused precipitation in glucose ascitic fluid agar. At this time it caused an intense green discoloration at the base of the blood agar slants around the water of condensation. By repeated animal passages this strain was three times made to revert abruptly to its original form (atypical Type IIa), both in cultural and serological reactions. An immune serum was prepared to each form of the strain, and each serum acted strongly on the homologous form, but was without action on the heterologous form of the strain. This mutation suggests that these pneumococci reacting with all three types of antipneumococcus sera may represent primitive, relatively undifferentiated forms from which the fixed types may have arisen.


1930 ◽  
Vol 51 (1) ◽  
pp. 123-147 ◽  
Author(s):  
Martin H. Dawson

1. Type-specific S pneumococci may be transformed from one specific S type into other specific S types through the intermediate stage of the R form. 2. R forms of pneumococi, derived from any specific S type, may be transformed into S organisms of other specific types by the following procedure:—The subcutaneous injection, in white mice, of small amounts of living R forms together with vaccines of heterologous S cultures. (i) S vaccines heated for 15' at temperatures between 60° and 80°C., are effective in causing R forms, derived from heterologous S types, to revert to the type of the vaccine. (ii) S vaccines heated for 15' at temperatures between 80° and 100°C., are not effective in causing R forms, derived from heterologous S types, to revert to the type of the vaccine. (iii) S vaccines heated for 15' at temperatures between 80° and 100°C., may cause 2 R and 3 R cultures to revert to their original S type. (iv) S vaccines of any type, including Type I, heated for 15' at temperatures between 80° and 100°C., are not effective in causing 1 R cultures to revert to their original S type. (v) S vaccines heated for periods as long as two hours at 60°C. are effective in causing R forms, derived from heterologous types, to revert to the type of the vaccine. 3. A single cell R strain, derived from a Type II S pneumococcus, has been successively transformed into a Type III S, a Type I S and a Group IV S culture. 4. Corresponding with the various degrees of "degradation" of the R form there are varying degrees of "development" of the S form. 5. The nature of the conditions responsible for alteration of type as induced by these procedures has been investigated and the causes responsible for the transformations are discussed. 6. All attempts to produce transformation of type in vitro have been unsuccessful. 7. The rô1e which the phenomenon of transformation of type may play in problems of infection and epidemiology is indicated.


1915 ◽  
Vol 22 (2) ◽  
pp. 248-268 ◽  
Author(s):  
Henry T. Chickering

1. The protective substances contained in specific precipitates from antipneumococcus serum can be extracted by suitable chemical and physical agents, dilute sodium carbonate at 42°C. being especially advantageous as an extractive agent. 2. The resulting water-clear extracts, when made up to the original volume of the serum used for precipitation, protect animals almost as well as does the whole serum. 3. The bacterial extracts used in precipitating the protective substances from the serum act specifically; that is, a bacterial extract of pneumococcus of Type I removes the protective substances from a Type I immune serum only. 4. In a polyvalent serum of Type I and Type II, the protective substances of each type may be removed independently of each other by the successive addition of the homologous antigens. 5. Extracts of specific serum precipitates contain only one-fiftieth to one-sixtieth of the protein in the original serum, and about one-half the protein of the whole precipitate. 6. Extracts contain not only protective substances but agglutinins and precipitins. 7. Extracts and whole precipitates not only confer passive immunity but stimulate the production of active immunity to pneumococcus infection in rabbits and mice.


1994 ◽  
Vol 197 (1) ◽  
pp. 429-436
Author(s):  
M Hedrick ◽  
S Katz ◽  
D Jones

The ventilatory patterns of air-breathing fish are commonly described as 'arrhythmic' or 'irregular' because the variable periods of breath-holding are punctuated by seemingly unpredictable air-breathing events (see Shelton et al. 1986). This apparent arrhythmicity contrasts with the perceived periodism or regularity in the gill ventilation patterns of some fish and with lung ventilation in birds and mammals. In this sense, periodism refers to behaviour that occurs with a definite, recurring interval (Bendat and Piersol, 1986). The characterisation of aerial ventilation patterns in fish as 'aperiodic' has been generally accepted on the basis of qualitative examination and it remains to be validated with rigorous testing. The bowfin, Amia calva (L.), is a primitive air-breathing fish that makes intermittent excursions to the air­water interface to gulp air, which is transferred to its well-vascularized gas bladder. Its phylogenetic position as the only extant member of the sister lineage of modern teleosts affords a unique opportunity to examine the evolution of aerial ventilation and provides a model for the examination of ventilatory patterns in primitive fishes. To establish whether Amia calva exhibit a particular pattern of air-breathing, we examined time series records of aerial ventilations from undisturbed fish over long periods (8 h). These records were the same as those used to calculate average ventilation intervals under a variety of experimental conditions (Hedrick and Jones, 1993). Their study also reported the occurrence of two distinct breath types. Type I breaths were characterised by an exhalation followed by an inhalation, whereas type II breaths were characterised by inhalation only. It was also hypothesized that the type I breaths were employed to meet oxygen demands, whereas the type II breaths were used to regulate gas bladder volume. However, they did not investigate the potential presence of a periodic ventilatory pattern. We now report the results of just such an analysis of ventilatory pattern that demonstrates a clear periodism to air-breathing in a primitive fish.


1920 ◽  
Vol 32 (3) ◽  
pp. 283-293 ◽  
Author(s):  
Ida W. Pritchett

1. No demonstrable antiopsonins are formed in rabbits following the intravenous injection of monovalent pneumococcus horse sera, Types I, II, and III. 2. The serum of rabbits injected with immune pneumococcus horse serum, Type I, II, or III, or with normal horse serum, when mixed in the proportion of 1:4 with Type I or Type II pneumococcus horse serum, can greatly augment, in vitro, the opsonization and agglutination of Type I and Type II pneumococci by the homologous immune horse sera. No similar effect is obtained with Type III serum and pneumococci. 3. The increase in opsonization and agglutination is dependent upon (a) specific sensitization of the pneumococci by the homologous immune serum and (b) the presence of the precipitating serum. In the absence of sensitization, as when a heterologous or normal horse serum is employed, opsonization and agglutination do not occur, even though a precipitating mixture is provided. The substitution of normal rabbit serum for the precipitating rabbit serum gives opsonization and agglutination in dilutions slightly higher than are effected with salt solution only, due possibly to the more favorable medium created for the leucocytes by the addition of 25 per cent of whole rabbit serum. 4. Different methods of combining the immune horse serum, precipitating rabbit serum, and pneumococci yield very similar results, preliminary sensitization of the bacteria before precipitation, or precipitation in the rabbit-horse serum mixture before the addition of the pneumococci for sensitization causing little if any difference in result from that obtained when immune horse serum, precipitating rabbit serum, and pneumococci are all mixed and incubated together. 5. This increased opsonization in the test-tube does not seem to be paralleled by increased protective power, or at any rate such protection is not readily demonstrated.


1951 ◽  
Vol 93 (3) ◽  
pp. 229-245 ◽  
Author(s):  
Frank L. Horsfall

The type specific immunological properties of certain non-hemolytic streptococci, including Str. salivarius type I and type II, present in the respiratory tract of human beings appear to be dependent upon the presence of capsular polysaccharides. The levans formed from sucrose by Str. salivarius (encapsulated S cells or non-encapsulated R variants), or by cell-free enzymes derived from these microorganisms, are indistinguishable immunologically and show no evidence of type specificity. Such levans appear to be immunologically distinct from and unrelated to the capsular polysaccharides of the microorganisms which produce them.


1928 ◽  
Vol 27 (2) ◽  
pp. 113-159 ◽  
Author(s):  
Fred Griffith

1. In the course of the examination of sputum from cases of lobar pneumonia, observations have been made on the incidence of the chief types of pneumococci. In the district from which the material was obtained, there was an apparent local diminution in the number of cases of lobar pneumonia due to Type II the figures were 326 per cent. of Type II cases in the period 1920–22, and only 74 per cent. in the period 1924–27. The incidence of Type I was approximately the same in the two periods, the percentages being 3O6 and 343.2. Several different serological varieties of pneumococci have been obtained from the sputum of each of several cases of pneumonia examined at various stages of the disease. This has occurred most frequently in cases of pneumonia due to Type I, and in two instances four different types of Group IV were found in addition to the chief types. The recovery of different types is facilitated by the inoculation of the sputum (preserved in the refrigerator), together with protective sera corresponding to the various types in the order of their appearance.3. Two interesting strains of Group IV pneumococci have been obtained from pneumonic sputnm.One was an R strain which produced typical rough colonies, yet preserved its virnlence for mice and its capacity to form soluble substance. This R pneumococcus developed a large capsnle in the mice, which died of a chronic type of septicaemia. A strain producing smooth colonies was obtained from it in the course of a prolonged series of passage experiments.The second strain, which was proved not to be a mixture, agglutinated specifically with the sera of two different types. In the peritoneal cavity of the mouse the specific soluble substance of each type was produced.4. A method of producing the S to R change through ageing of colonies on chocolate blood medium containing horse serum is described. After two to three days' incubation small rough patches appear in the margins of the smooth colonies, and from these pure R strains can be isolated.5. It has been shown that the R change is not equally advanced in the descendants of virulent pneumococci which have been exposed to the action of homologous immune serum. Some R strains form traces of soluble substance in the peritoneal cavity of the mouse; these revert readily to the virulent S form and, in addition, are able to produce active immunity. Others show no evidence of S antigen; spontaneous reveraion takes place with difficulty, if at all, and they are incapable of producing active immunity. The stronger the immune serum used, the more permanent and complete is the change to the R form.6. Restoration of virulence to an attenuated R strain, with recovery of the S form of colony and of the original serological type characters may be obtained by passage through mice. The change from the R to the S form is favoured by the inoculation of the R culture in large doses into the subcutaneous tissues; but the most certain method of procuring reversion is by the inoculation of the R culture, subcutaneously into a mouse, together with a large dose of virulent culture of the same type killed by heat. Incubation of such a mixture in vitro does not induce reversion.7. Reversion of an R strain to its S form may occasionally be brought about by the simultaneous inoculation of virulent culture of another type, especially when this has been heated for only a short period to 60° 0., e.g. R Type II to its S form when inoculated with heated Type I culture.8. Type I antigen appears to be more sensitive to exposure to heat than Type II antigen, since the former loses the power to cause reversion when heated to 80° C., whereas Type II culture remains effective even after steaming at 100°C.9. The antigens of certain Group IV strains appear to be closely related to that of Type II, and are equally resistant to heat. Steamed cultures of these Group IV strains cause the R form derived from Type II to revert to its S form, while they fail to produce reversion of the R form derived from Type I.10. The inoculation into the subcutaneous tissues of mice of an attenuated R strain derived from one type, together with a large dose of virulent culture of another type killed by heating to 60° C., has resulted in the formation of a virulent S pneumococcus of the same type as that of the heated culture.Thp newly formed S strain may remain localised at the seat of inoculation, or it may disseminate and cause fatal septicaemia.The S form of Type I has been produced from the R form of Type II, and the R form of Type I has been transformed into the S form of Type II.The clear mucinous colonies of Type III have been derived both from the R form of Type I and from the R form of Type II, though they appear to be produced more readily from the latter. The newly formed strains of Type III have been of relatively low virulence, and have frequently remained localised at the subcutaneous seat of inoculation.Virulent strains of Types I and TI have been obtained from an R strain of Group IV.11. Heated R cultures injected in large doses, together with small doses of living R culture have never caused transformation of type, and only rarely produced a reversion of the R form of Type II to its virulent S form.12. The results of the experiments on enhancement of virulence and on transformation of type are discussed and their significance in regard to questions of epidemiology is indicated.


1933 ◽  
Vol 58 (2) ◽  
pp. 245-252 ◽  
Author(s):  
James B. Graeser ◽  
M. Cornwell Harrison

Fifty-five individuals were tested to determine the pneumococcidal promoting activity of their serum against Types I and II pneumococci. By repeated tests an attempt was made to study the constancy of the degree of their immunity over intervals of 2 to 6 months. In this group were included nine persons with common colds and twelve cases of a severe influenza-like infection. Fifteen of the fifty-five cases showed a change in titer of their humoral immunity against either Type I or Type II or both. Three of these showed an increase, and twelve a decrease. This reaction in most instances was a specific one in that the altered reaction toward one type was not associated with a similar change toward the other type pneumococcus. Colds and influenza-like infections apparently exerted no effect upon the titer of humoral immune substances.


Sign in / Sign up

Export Citation Format

Share Document