Bacterial chromosomal mobility via lateral transduction exceeds that of classical mobile genetic elements

Abstract

It is commonly assumed that the horizontal transfer of most bacterial chromosomal genes is limited, in contrast to the frequent transfer observed for typical mobile genetic elements. However, this view has been recently challenged by the discovery of lateral transduction in Staphylococcus aureus, where temperate phages can drive the transfer of large chromosomal regions at extremely high frequencies. Here, we analyse previously published as well as new datasets to compare horizontal gene transfer rates mediated by different mechanisms in S. aureus and Salmonella enterica. We find that the horizontal transfer of core chromosomal genes via lateral transduction can be more efficient than the transfer of classical mobile genetic elements via conjugation or generalized transduction. These results raise questions about our definition of mobile genetic elements, and the potential roles played by lateral transduction in bacterial evolution.

Fig. 1. Lateral transduction of chromosomal DNA.

LT is initiated during the early stages of prophage activation with the prophage remaining integrated in the bacterial chromosome. The mechanism commences with bidirectional in situ replication of the integrated prophage from the phage ori, generating multiple copies of the integrated phage and surrounding bacterial chromosome [1]. Some prophages subsequently excise from the chromosome to generate progeny via the lytic cycle, but in those that remain integrated, the phage small terminase subunit (TerS) recognises the embedded pac site (pink triangle) within the prophage sequence, forming a complex for delivery of the DNA to the large terminase (TerL) subunit [2]. The TerS:DNA complex associates with the large terminase (TerL) subunit, which cleaves and translocates the DNA into available phage capsids until capacity (one headful) is reached, with the initial capsid containing a mixture of phage and chromosomal DNA [3]. When the capsid is filled, the DNA is cleaved once more and the Terminase:DNA complex associates with a new empty capsid to resume the packaging process, generating many processive headfuls containing bacterial chromosomes for subsequent transduction [4].

Fig. 2. Genetic mobility via different mechanisms in S. aureus.

a Transfer frequencies per donor cell and b relative frequency of genetic mobility (defined as transfer frequency × cargo capacity) of different genetic elements by transfer type. Transfer of chromosomal DNA by phage 80α via generalised (GT) or lateral (LT) transduction of a cadmium resistance marker located at defined distances from the phage attachment site, conjugative transposons (Conj. Tn), phages, PICIs and plasmids. Data were extracted from literature or acquired through experimentation (see Table 1 for details).

Fig. 3. Genetic mobility via different mechanisms in Salmonella spp.

a Transfer frequencies per donor cell and b relative frequency of genetic mobility (defined as transfer frequency × cargo capacity) of different genetic elements by transfer type. Transfer of chromosomal DNA by phage P22 via generalised (GT) or lateral (LT) transduction of a tetracycline resistance marker located at defined distances from the phage attachment site, conjugative transposons (Conj. Tn), phages and plasmids. Data were extracted from literature or acquired through experimentation (see Table 3 for details).

Fig. 4. Potential for extensive DNA transfer via lateral transduction is dictated by the distribution of prophage attachment sites in the bacterial chromosome.

Map of the chromosomes of S. aureus NCTC8325-4 (a) and S. Typhimurium LT2 (b) indicating the ten potential chromosomal attachment (attB) sites available for prophage integration. The packaging direction of an integrated prophage from each attB site is indicated by its corresponding colour-coded arrow, with the dashed regions representing a distance of approximately seven headfuls (one headful = ~45 kb for 80α) in S. aureus, or 12 headfuls (one headful = ~43 kb for P22) in S. Typhimurium from the attB site, which is the minimum distance known to be packaged by LT for each phage. a The distribution and directionality of attB sites in the S. aureus NCTC8325-4 chromosome indicates the potential for transfer of the entire region between ~0.31 and 2.0 Mb from a poly-lysogenic background, representing approximately 58% of the bacterial chromosome. Adapted from ref. . b The distribution and directionality of attB sites in S. Typhimurium LT2 indicates the potential for transfer of up to 3.5 Mb of chromosomal DNA from a poly-lysogenic background, representing approximately 72% of the bacterial chromosome. Source data are provided as a Source Data file.