Salmonella choleraesuis strains deficient in O antigen remain fully virulent for mice by parenteral inoculation but are avirulent by oral administration.

O-antigen-deficient derivatives of two mouse-virulent strains of Salmonella choleraesuis (serogroup C1; O-6,7) were constructed by transduction of a long deletion of the rfb operon. Strains SN36 and SN57 were derived from the smooth ancestor SL2824, while SN37 was derived from the smooth ancestor SL2840. These rfb deletion derivatives (rfb strains) had typical bacteriophage sensitivity patterns of "rough" Salmonella strains and were at least 200,000 times more sensitive to serum than their smooth ancestors. Lipopolysaccharides (LPS) extracted from them consisted only of two low-molecular-weight bands and lacked the ladderlike pattern of bands seen in the LPS of their smooth ancestors. The LPS from the rfb strains did not react in an enzyme immunoassay with any of three monoclonal antibodies directed against different epitopes of the O-6,7 antigen but reacted well with at least one of three monoclonal antibodies specific for core epitopes. The data were consistent with inability of these strains to synthesize O-specific chains and showed that the LPS extracted from SN57 was of chemotype Ra and that from SN36 was of chemotype Rb1, while that of SN37 consisted of a mixture of the two chemotypes. The virulence of these strains was tested by various routes in BALB/c mice. All three O-antigen-deficient derivatives were about as virulent as their "smooth" ancestors by the intraperitoneal and intravenous routes (50% lethal dose, 20 to 700 bacteria) but, unlike their ancestors, were avirulent by the oral route (50% lethal dose, greater than or equal to 5 x 10(9) bacteria). This suggests that the major role of smooth LPS in the mouse virulence of S. choleraesuis is to facilitate survival in the gastrointestinal tract and eventual entry into deeper tissues.