Date Published: August 8, 2019
Publisher: Public Library of Science
Author(s): Yin Ning Chiang, José R. Penadés, John Chen, Kimberly A. Kline.
Bacteriophages, or phages, are the viruses of bacteria. They are obligate intracellular parasites whose existence is fatefully coupled to the success and survival of the hosts they infect and kill. Known to be the most abundant biological entities on the planet, phages are pervasive to almost all microbial communities, in which they play central roles in moderating bacterial populations and mediating horizontal gene transfer. When phages propagate, they can sometimes encapsidate host bacterial DNA to form transducing particles. Transducing particles are ostensibly like mature phage particles, only they eject bacterial DNA instead of a viral genome when they infect other cells. The DNA can then recombine into the chromosome or replicate as a plasmid in the new host cell. This process of transferring bacterial DNA from one bacterium to another is known as genetic transduction.
Lysogenic bacteria are host cells that carry one or more prophages. Prophages are latent temperate phages that are most often stably integrated into the host bacterium’s genome, where they replicate passively as DNA during cell division. Phage development occurs in the lytic cycle following host cell infection or prophage induction from the lysogenic cycle (Fig 1). Transducing particles are also formed in the lytic cycle, and the acquisition of their content depends on the type of DNA packaging mechanism (pac or cos) utilized by the phage.
Generalized transduction, discovered in Salmonella phage P22, was the first mechanism of phage-mediated gene transfer to be identified . It is the process by which phages can package any bacterial DNA (chromosomal or plasmid) and transfer it to another bacterium. The transducing particles of this mode of transduction form when bacterial host DNA is packaged into phage heads instead of viral DNA. One of the early models for how this occurs proposed that the host bacterial genome is degraded into fragments in the lytic cycle so that phage heads could package the smaller DNA pieces of suitable length. However, this theory turned out to be inaccurate because phages capable of generalized transduction are not known to cause the breakdown of the bacterial chromosome into phage-sized or smaller DNA fragments [9, 10]. Curiously, this model remains the most commonly depicted in diagrams and summary figures of generalized transduction, though it has yet to be substantiated.
The generalized and specialized modes of transduction are commonly viewed as missteps made by phages that result in the packaging of host DNA. Mistakes in pac site recognition are relatively rare, and errors in prophage excision even more so, and these are reflected in the low frequencies of host gene transfer normally observed for both mechanisms. Recently, the third mechanism of transduction, lateral transduction, was discovered in the temperate phages of Staphylococcus aureus . Unlike its predecessors, lateral transduction does not appear to be the result of an erroneous phage process. On the contrary, it seems to be a natural part of the phage life cycle . The key here is that the staphylococcal prophages do not follow a typical lytic program but instead excise late in their life cycle. This results in a mode of transduction that transfers bacterial chromosomal DNA at frequencies at least 1000-fold greater than previously observed.
Phages are the most abundant gene-transfer particles in nature, and some mobile genetic elements have evolved to use that to their advantage. The S. aureus pathogenicity islands (SaPIs) are highly mobile genetic elements that carry genes for toxic shock toxin and other virulence factors [19, 20]. They are molecular parasites that exploit certain temperate phages as helpers for their own production and dissemination. Normally, they are integrated in the host bacterial chromosome until they are induced to excise and replicate by helper phage–encoded antirepressor proteins. SaPI-encoded small terminases then form hetero-oligomers with phage large terminases to form new terminase enzymes that recognize SaPI pac sites (instead of phage pac sites), enabling SaPIs to hijack the phage packaging machinery to encapsidate their own genomes into infective phage-derived particles that are transferred at extremely high frequencies, both intra- and intergenerically (Fig 3) [21, 22]. Moreover, SaPI-like elements appear to be widespread, as phage-inducible chromosomal islands (PICIs) have now been discovered in both gram-positive and gram-negative bacteria [23, 24].
With the rise of superbug strains that are progressively more virulent and antibiotic resistant, the importance of understanding the drivers of bacterial evolution has never been so apparent. Now, with three modes of phage transduction, we are just beginning to appreciate that genetic transduction occurs on a scale that is far greater than we ever imagined. Remarkably, phage-mediated gene transfer may be just the tip of the iceberg when it comes to genetic transduction. The PICIs are a widely distributed family of mobile genetic elements that exploit phages for their own reproduction and transfer [23, 24]. As more and more biology of the PICIs is revealed, such as mechanisms of phage parasitism or noncanonical genetic transduction, their impact on genetic transduction and bacterial evolution may prove to be profound and expansive.