Recombination of Salmonella phase 1 flagellin genes generates new serovars

Abstract

To determine the evolutionary mechanisms generating serotypic diversity in Salmonella strains, we sequenced the central, antigen-determining part of the phase 1 flagellin gene (fli) in strains of several serovars for which estimates of chromosomal genomic relatedness had been obtained by multilocus enzyme electrophoresis. The nucleotide sequence of this region was identical in several chromosomally divergent strains of Salmonella heidelberg (phase 1 antigen r) but differed by 19% from the corresponding and similarly invariant sequence in strains of the closely related serovar SalmoneUa typhimurium (phase 1 antigen 'l. Mutational drift of the sequence present in the common ancestor is unlikely to have generated the difference between the phase 1 flageilins of these two serovars, which we attribute instead to a recombination event. This interpretation is supported by evidence that Salmonella strains of very diverse chromosomal backgrounds but similar phase 1 antigens may have closely similar nucleotide sequences for this highly polymorphic region. We suggest that lateral transfer and recombination of phase 1 flagellin genes is a major evolutionary mechanism generating new SalmoneUa serovars.Bacteria of the genus Salmonella are motile by means of peritrichous flagella, the filaments of which are composed of a highly antigenic protein, flagellin. There are two sources of antigenic diversity in Salmonella flagellins. First, there is a complex system of regulation causing two genes encoding structurally distinct flagellins (phase 1 and phase 2) to be alternatively expressed (23); second, the central, antigenic part of the flagellin protein is highly polymorphic in amino acid sequence (24,35,36). The phase 1 flagellin is encoded by the fliC gene, and the phase 2 flagellin is encoded by the fljB gene (15). More than 50 phase 1 flagellins and 30 phase 2 flagellins have been distinguished serologically (22), and this extensive diversity, together with antigenic variation in the somatic (0) lipopolysaccharide, has, for more than half a century, provided the basis for identification and classification of strains in the Kauffmann, White serotyping scheme (8,19,21).Comparison of the nucleotide sequences of the phase 1 flagellin locus (fliC) in strains of five Salmonella serovars has shown marked variation in the rate of evolution in different portions of the gene (30,35,36). This can be seen when the gene is divided into three segments of approximately equal length. The sequences encoding the carboxy-and aminoterminal regions of the protein, which are important for polymerization and secretion (14), are highly conserved among allelic forms (35,36), but the central region varies markedly in both sequence and length among strains of different serovars (30,35,36). The central portion of the protein has been implicated as the site of the major antigenic epitope, which suggests that this region is exposed on the surface of the flagellum (16,17), and electron micrographs of the flagellum of Salmonella typhimurium have shown that th...

Acquisition and rearrangement of sequence motifs in the evolution of bacteriophage tail fibres

“…In recent years, a number of polymorphic loci in Escherichia coli and Salmonella containing genes for surface proteins or metabolic enzymes under high selective pressure have been studied, and evidence for the horizontal transfer of gene segments was found (DuBose et al. 1988;Stoltzfus et al, 1988;Smith et al, 1990;Bisercic et al, 1991;Reeves, 1993). It is likely that bacteria and their viruses share, at least in part, the recombination functions involved in horizontal transfer of gene segments, and hence studies on the gene evolution of bacteriophages might also be of relevance in the study of their host bacteria.…”

“…This X sequence might therefore be an efficient recombination site, since the left half-site exhibits only one mismatch to the consensus half-site. On the long tall-fibre gene of T4, a crossover site-like sequence which is displaced from the G* segment by 114bp has been identified as a potential recombination site (Snyder and Wood, 1989). However, it exhibits 11 mismatches to the consensus and might be selected for recombination by the currently known DNA invertases only at a very low frequency.…”

Molecular evolutionary genetics of the cattle-adapted serovar Salmonella dublin

“…To determine the molecular basis for this difference, we undertook a comparative study of the sequence of the fliC gene, which encodes phase 1 flagellin (41,42). Variation in the sequence of the 1,518-nucleotide-coding region of the fliC gene among one isolate of S. enteritidis, three isolates of S. dublin, and an isolate of serotype 1,9,12:g,m,p:-) is shown in Table 4.…”

Host adapted serotypes of Salmonella enterica

“…Within subspecies enterica, some serotypes are polyphyletic ; identical serotypes occur among isolates of distantly related clones that also differ in pathogenic potential and host range. This can be attributed to horizontal genetic transfer and recombination of antigen genes between lineages, an event that has been proposed to happen with relatively high frequency [22]. However, overall the subspecies remain clonal [23].…”