Antigenic modulation ofBordetella pertussis

Abstract

The antigenic structure ofBordetella pertussisvaries continuously with environmental conditions of growth and, under suitable conditions, any of three forms (or modes) with markedly different antigenic surfaces may be developed. High temperatures and certain ions, such as sodium, potassium, halides, formate and nitrate, favour growth like that on Bordet and Gengou's medium at 35° C. Low temperatures and other ions, such as magnesium, sulphate and mono- and dicarboxylic acids with more than two carbon atoms, favour growth with a markedly different antigenic structure and character. These two extreme forms have been called X mode and C mode respectively. A third mode (called I mode) is induced within a narrow range of intermediate temperatures and ion ratios. Bacterial cells in C mode, unlike those in X mode, do not agglutinate red-blood cells, are not haemolytic or agglutinable by heavy metal salts, have no surface antigen related toBordetella parapertussisorB. bronchisepticaand are serotypically homogeneous.The influence of ions is a function of their species and ratios and not of their absolute concentrations or total ionic strength. A number of ions has been arranged in a pattern. In this the influence of any salt is represented at the centre of a line joining its component ions, and a measure of the influence of any salt mixture is given by the position of its imaginary centre of inertia. (For calculating this,massis represented by the product of salt concentration and conductance ratio andradius of gyrationby distance.) The influences of ions and temperature appear not to interact since their combined influence is proportional to the sum of their separate influences.The change from one mode to another (modulation) occurs without mutation or selection, is complete within 7–15 cell divisions and appears to stem from altered rates of synthesis of at least three kinds of antigen molecule. During the process of modulation, antigens not detectable by agglutination in any of the three equilibrium modes (X, I and C) may appear transiently at the surface.Mutants may or may not modulate. Modulatable mutants may be distinguishable from the wild type in only one mode. Almost all convalescent antibodies are directed against X mode, but C-mode antibodies have been found in several adults with persistent cough and infection.I wish particularly to thank Dr E. K. Andersen for her generous gifts of sera, Drs P. L. Kendrick, H. Proom, A. F. B. Standfast and A. J. H. Tomlinson for gifts of cultures and Mr M. Breach for his invaluable help in the preparation of media and sera. I am also indebted to the University of London Central Research Fund and the Governors of Westminster Hospital for grants towards the purchase of materials.