The effects of O-antigen character and enterobacterial common antigen content on the in vivo persistence of aromatic-dependent Salmonella sp. live-vaccine strains

Abstract

Aromatic-dependent ( aro) derivatives of Salmonella choleraesuis like am S. typhimurium are non-virulent but, unlike them, are ineffective as live vaccines in mice, given i.p. An aro derivative of S. choleraesuis did not persist in the liver and spleen (RES) of mice after i.p. inoculation whereas a similar derivative of S. typhimurium persisted. S. choleraesuis (O group C 1; O-6,7) and S. typhimurium [O group B; O-(1),4(5), 12] differ in O antigen of LPS, determined by chromosomal locus, rfb. Three pairs of nearly-isogenic aro derivatives, one member O-6,7 and the other 0-(1),4,(5),12, were constructed in two lines of S. typhimurium by replacement of their B- rfb genes with the C 1- rfb genes of S. choleraesuis. In tests for persistence after mixed or separate i.p. inoculation of equal doses into BALB/c mice the O-(1),4,(5), 12 member of each pair was recovered as CFU in the RES at ca. 100-fold greater number than the O-6,7 member at 24 hours post-inoculation and subsequently. O-6,7 derivatives of S. typhimurium constructed as described above by a simple replacement of group B with group C- rfb locus synthesise only trace ( tr) amounts of enterobacterial common antigen (ECA). An ECA + (able to make normal levels of ECA) derivative of one aro, O-6,7 S. typhimurium strain was constructed by replacement of its B- rfe locus with the C- rfe locus of S. choleraesuis. Tested by mixed inoculation i.p. this strain persisted in the RES in numbers 10-fold greater than its O-6,7 ECA tr but 5–10fold lesser than its O-(1),4,(5),12 cousins. Thus both O-specificity and ECA contribute to the survival of salmonella species in mice as determined by in vivo persistence of non-multiplying aro derivatives.