Trends in Genetics
Volume 32, Issue 2, February 2016, Pages 114-126
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Review
The Floating (Pathogenicity) Island: A Genomic Dessert

https://doi.org/10.1016/j.tig.2015.11.005Get rights and content

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Three major types of horizontal gene transfer systems use radically different strategies for gene transfer at widely varying frequencies. Integrative and conjugative elements (ICEs) initiate their own transfer autonomously, staphylococcal pathogenicity islands (SaPIs) depend on helper phages, and gene-transfer agents (GTAs) generate and release tiny DNA-containing particles.

GTAs and SaPIs were probably derived from prophages by complementary deletions. ICEs were probably derived from integrated conjugative plasmids by ‘trading’ replication for integration/excision.

SaPIs interfere with their helper phages by three carefully regulated strategies to ensure high-frequency transfer.

SaPIs mediate generalized transduction while in situ independently of their self-transfer.

SaPIs and their relatives in Gram-positive cocci exist as cohesive and widespread families, as shown by orthology analysis of their hypothetical proteins, a method newly described for this review.

Among the prokaryotic genomic islands (GIs) involved in horizontal gene transfer (HGT) are the classical pathogenicity islands, including the integrative and conjugative elements (ICEs), the gene-transfer agents (GTAs), and the staphylococcal pathogenicity islands (SaPIs), the primary focus of this review. While the ICEs and GTAs mediate HGT autonomously, the SaPIs are dependent on specific phages. The ICEs transfer primarily their own DNA, the GTAs exclusively transfer unlinked host DNA, and the SaPIs combine the capabilities of both. Thus the SaPIs derive their importance from the genes they carry (their genetic cargo) and the genes they move. They act not only as versatile high-frequency mobilizers but also as mediators of phage interference and consequently are major benefactors of their host bacteria.

Section snippets

GIs and their mobility

GIs (see Glossary) in prokaryotes are discrete inserted DNA segments, many of which are mobile, carry genes that impact the pathobiology of their host organisms, and contribute significantly to host fitness 1, 2. Three major classes are the SaPIs, the GTAs, and the ICEs. The first two were probably derived from ancestral prophages and have retained certain key elements of the prophage design. The third group was almost certainly derived primarily from conjugative plasmids, acquiring other

The SaPI Story

The story begins with the notorious outbreak of toxic shock syndrome in the early 1980s related to high-absorbency menstrual tampons. The syndrome was soon attributed to a newly discovered staphylococcal toxin, TSST-1 [10]. As a cause of death among healthy young women and as one of the first known bacterial superantigens, TSST-1 occasioned considerable clinical and experimental interest [11], eventually leading to its cloning [12], sequence determination, and genetic analysis 13, 14. It was

The SaPI Lifestyle

SaPIs are maintained in the integrated state by a master repressor, Stl, that is analogous to the λc1 repressor but is not inducible by the SOS response to DNA damage [16]. This repressor is counteracted by helper phages, which encode specific, nonessential antirepressor proteins. These bind to the repressor and induce the repressor-controlled SaPI excision, replication, and packaging cycle. Repressor–antirepressor interactions are SaPI and phage specific. For example, one helper phage (80α)

Accessory Genes

Accessory genes, including genes for superantigens and other virulence and resistance factors, have evidently been inserted into the SaPIs by an unknown non-homology-based recombination mechanism. A remarkable case is that of tst (TSST-1) and seb (enterotoxin B), which are each inserted at precisely the same site in SaPI1 and SaPI3, respectively, but in opposite orientations [32].

Our detailed understanding of the basic molecular biology of the SaPIs has confirmed their nature as remarkable

Transgeneric SaPI Transfer

SaPIs as well as certain staphylococcal plasmids can be transferred at very high frequencies to Listeria monocytogenes, where they integrate into sites that resemble their secondary att sites in S. aureus [30]. A compendium of secondary att sites in S. aureus and in L. monocytogenes is shown in Figure S4. Additionally, staphylococcal plasmids are maintained autonomously in L. monocytogenes. Since the helper phage cannot replicate in L. monocytogenes [30], transgeneric transfer represents a

Phage Interference and its Mechanisms

All SaPIs thus far analyzed interfere with the reproduction of their helper phages. Although bacteria and other mobile elements block phage reproduction as a defense against phage predation, the SaPIs interfere to gain an advantage over their helpers. Their own reproduction demands that they do not disable the production of virion proteins and lysins. Thus far, three different interference mechanisms have been identified and characterized and are used in different combinations by different

SaPI-Mediated Generalized Transduction

Generalized transduction, which is mediated by pac phages, involves the recognition of pac-site homologs (pseudo-pac sites) resulting in mispackaging of host DNA. Typically about 1% of pac phage particles carry host DNA, resulting in a transduction frequency of about 10−7 for the average host gene. Unsurprisingly, pseudo-pac sites recognized by the SaPI TerS also occur with considerable frequency, also resulting in mispackaging of host DNA [40]. Pseudo-pac sites vary greatly in their

SaPI Occurrence and Evolution

As described in the first part of this review, the SaPIs have developed a set of shared properties that sharply differentiates them from their putative prophage progenitor. A genome-based analysis suggests that they have spread widely and diversified while retaining their distinctive biotype.

SaPI-Like Elements in Other Bacteria

This evolutionary paradigm is not exclusive to the staphylococci: unsurprisingly, SaPI-like elements occur widely throughout the bacterial world. These were first identified in other Gram-positive cocci [44] and more recently it has been observed that streptococci and lactococci possess large families of phage-related elements genomically highly similar to the SaPIs. They have orthology patterns similar to those of the SaPIs in which elements in their own families appear first and those in

Concluding Remarks: Significance of GIs in HGT

In this review we have touched on three major types of GIs that have all developed from pre-existing and widespread mobile elements, namely prophages and conjugative plasmids. Although each represents a successful evolutionary adaptation, they have radically different roles in HGT and in the economy of their host bacteria. Thus, the conjugative GIs, which initiate and effect their self-transfer autonomously, may be quite large and carry a wide variety of virulence and adaptivity genes. These

Glossary

Clustered regularly interspaced short palindromic repeats (CRISPRs)
responsible for bacterial immunity against invading genetic units such as bacteriophages.
Competence (com)
the genetically determined natural ability to take up and incorporate free DNA (i.e., transformation).
Conjugation
mode of intercellular bacterial DNA transfer involving cellular attachment followed by transfer of a single-stranded DNA molecule generated by rolling-circle replication.
cos site
specific sequence cleaved by the

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