The Floating (Pathogenicity) Island: A Genomic Dessert

Novick, Richard P.; Ram, Geeta

doi:10.1016/j.tig.2015.11.005

Cited by 60 publications

(56 citation statements)

References 64 publications

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“…Notably, the TnSmu2 genes were previously shown to be downregulated in the strain lacking lytS, located upstream of lrgAB and known to positively regulate lrgAB expression (16). GIs are ubiquitous in prokaryotes and are acquired by horizontal gene transfer (45,46). They normally carry genes that encode a variety of functions responsible for adapting to a particular set of environmental conditions.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Streptococcus mutans Cid/Lrg System through CidB Function

Ahn

Rice

2016

Appl Environ Microbiol

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The Streptococcus mutans lrgAB and cidAB operons have been previously described as a potential model system to dissect the complexity of biofilm development and virulence of S. mutans. Herein, we have attempted to further characterize the Cid/Lrg system by focusing on CidB, which has been shown to be critical for the ability of S. mutans to survive and persist in a nonpreferred oxygen-enriched condition. We have found that the expression level of cidB is critical to oxidative stress tolerance of S. mutans, most likely by impacting lrg expression. Intriguingly, the impaired aerobic growth phenotype of the cidB mutant could be restored by the additional loss of either CidA or LrgA. Growth-dependent expression of cid and lrg was demonstrated to be tightly under the control of both CcpA and the VicKR two-component system (TCS), regulators known to play an essential role in controlling major catabolic pathways and cell envelope homeostasis, respectively. RNA sequencing (RNA-Seq) analysis revealed that mutation of cidB resulted in global gene expression changes, comprising major domains of central metabolism and virulence processes, particularly in those involved with oxidative stress resistance. Loss of CidB also significantly changed the expression of genes related to genomic islands (GI) TnSmu1 and TnSmu2, the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas system, and toxin-antitoxin (T/A) modules. Taken together, these data show that CidB impinges on the stress response, as well as the fundamental cellular physiology of S. mutans, and further suggest a potential link between Cid/ Lrg-mediated cellular processes, S. mutans pathogenicity, and possible programmed growth arrest and cell death mechanisms. IMPORTANCEThe ability of Streptococcus mutans to survive a variety of harmful or stressful conditions and to emerge as a numerically significant member of stable oral biofilm communities are essential elements for its persistence and cariogenicity. In this study, the homologous cidAB and lrgAB operons, previously identified as being highly balanced and coordinated during S. mutans aerobic growth, were further characterized through the functional and transcriptomic analysis of CidB. Precise control of CidB levels is shown to impact the expression of lrg, oxidative stress tolerance, major metabolic domains, and the molecular modules linked to cell death and lysis. This study advances our understanding of the Cid/Lrg system as a key player in the integration of complex environmental signals (such as oxidative stress) into the regulatory networks that modulate S. mutans virulence and cell homeostasis. Streptococcus mutans, a significant constituent of cariogenic oral biofilms, is capable of withstanding a variety of stressors encountered in the oral cavity. The ability of this bacterium to efficiently and rapidly adjust to the dynamic oral environment is essential for its pathogenic lifestyle. Oxidative stress is one of the most important environmental variables affecting the pathogenic pot...

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Section: Discussionmentioning

confidence: 99%

Understanding the Streptococcus mutans Cid/Lrg System through CidB Function

Ahn

Rice

2016

Appl Environ Microbiol

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“…A glance at the SaPI genome organization and the list of SaPI genes indicates an obvious relation to the prophage genome and genes (see references [17, 33] and, especially [4] for comparative diagrams– indeed, SaPIs have generally been annotated as defective prophages and their genes as phage genes. Although there is clearly an ancestral relation, we consider it very distant for the following reasons: i) the SaPIs are a coherent family, within which the similarities between SaPI genes are much greater than similarities between SaPI and phage genes or genes of other genetic elements [2, 4]; ii) they possess genes that are shared among SaPIs but are not found elsewhere, especially the hypothetical genes, and the interference genes, of which the latter are all located in the same region of the island, a region that has probably been imported [2, 4]; iii) they share a rare (though not absolutely unique) biological functionality – the property of being induced by prophage anti-repressor genes; iv) they occupy unique SaPI-specific att sites that are conserved throughout the staphylococci and are never occupied by other elements; v) they carry certain accessory genes that are not found on other genetic elements.…”

Section: Evolutionmentioning

confidence: 99%

“…Some carry identifiable accessory genes, especially fusidic acid resistance in S. epidermidis [34]. Similarly, large families of SaPI-like elements have been identified in the genomes of lactococci, pneumococci, and streptococci [2, 4] [35]; functionality has yet to be demonstrated for any of those in lactococci and pneumococci. Enterococcus faecalis strain V583 possesses the only SaPI-like-like element, EfCIV583, outside of the staphylococci whose SaPI-like functionality has been demonstrated [33] [2]: it is induced by a helper phage (Φ1) whose xis gene is the de-repressor, is packaged in small particles, is transferred at high frequency, and interferes with its helper phage.…”

Section: Other Speciesmentioning

confidence: 99%

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Staphylococcal pathogenicity islands — movers and shakers in the genomic firmament

Novick

Ram

2017

Current Opinion in Microbiology

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The staphylococcal pathogenicity islands (SaPIs) are highly mobile 15 kb genomic islands that carry superantigen genes and other virulence factors and are mobilized by helper phages. Helper phages counteract the SaPI repressor to induce the SaPI replication cycle, resulting in encapsidation in phage like particles, enabling high frequency transfer. The SaPIs split from a protophage lineage in the distant past, have evolved a variety of novel and salient features, and have become an invaluable component of the staphylococcal genome. This review focuses on recent studies describing 3 different mechanisms of SaPI interference with helper phage reproduction and other studies demonstrating that helper phage mutations to resistance against this interference impact phage evolution. Also described are recent results showing SaPIs contribute in a major way to lateral transfer of host genes as well as enabling their own transfer. SaPI-like elements, readily identifiable in the bacterial genome, are widespread throughout the Gram-positive cocci, though functionality has thus far been demonstrated for only a single one of these.

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“…Transduction by bacteriophages is the main mechanism of transfer of genes encoding virulence factors and antibiotic resistance in S. aureus [2]. Specific "helper" phages are also capable of high frequency mobilization of S. aureus pathogenicity islands (SaPIs), disseminating the virulence factors the SaPIs carry [3]. Phage 80α is a model of S. aureus-infecting siphoviruses and is capable of both generalized transduction and specialized transduction of SaPIs [4].…”

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confidence: 99%

Structure and Function of the Staphylococcus aureus Bacteriophage 80α Baseplate

et al. 2017

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Staphylococcus aureus is an opportunistic human pathogen [1], and a public health threat due to the increased incidence of antibiotic resistance. Transduction by bacteriophages is the main mechanism of transfer of genes encoding virulence factors and antibiotic resistance in S. aureus [2]. Specific "helper" phages are also capable of high frequency mobilization of S. aureus pathogenicity islands (SaPIs), disseminating the virulence factors the SaPIs carry [3]. Phage 80α is a model of S. aureus-infecting siphoviruses and is capable of both generalized transduction and specialized transduction of SaPIs [4]. The phage baseplate is used for recognition and adhesion to target cells; however, very little is known about these structures in staphylococcal phages. 80α tails were produced from a mutant phage with a deletion of residues 2-13 of the scaffolding protein (Fig. 1a). Cryo-electron microscopy was carried out using an FEI Titan Krios electron microscope with a DE-20 Direct Detection Device at the Biological Science Imaging Resource at Florida State University. Three-dimensional reconstruction was done using EMAN and EMAN2 [5] with six-fold (c6) symmetry applied. The resolution of the final model (Fig. 1c) was 8.8 Å according to the 0.143 FSC criterion, limited by the small number of particle images used (7000).The 80α baseplate is encoded by at least six genes (Fig. 1b). Some of these can be identified by comparison with other phages [6]. HHpred matched 80α gp58 to the crystal structure of Bacillus subtilis phage SPP1 distal tail protein (Dit) [7], which best fit into the upper core of the baseplate reconstruction (Fig. 1d). gp59 is thought to correspond to the tail spike protein (Tal) of Lactococcus lactis phage p2 [8], but could not be reliably fitted to the baseplate reconstruction. 80α gp61 is nearly identical to S. aureus phage ϕ11 receptor binding protein (RBP) gp45, and its crystal structure[9] fits into six distinctive peripheral features of the baseplate. 80α gp62 (central tail fiber; FibC) matches the N-terminal domain of SPP1 baseplate upper protein (BppU) [10], followed by a coiled-coil region that could be fitted into the only extended fibrous features of the baseplate reconstruction, and a C-terminal region that also matched the ϕ11 RBP. 80α gp67 matches several hydrolytic enzymes and may constitute part of the unassigned baseplate core. 80α gp68 includes the same N-terminal region as FibC, followed by a collagen-like triple helix. This protein most likely forms additional outer tail fibers (FibO), but could not be distinguished in the baseplate reconstruction. ϕ11 adsorption to S. aureus requires either α-or β-GlcNAc residues attached to wall teichoic acids, suggesting these are receptors for ϕ11 and presumably for 80α [11]. As expected, an 80α Δorf61 strain lacking RBP was not viable. A Δorf62 strain lacking FibC was also not viable, suggesting that host recognition and adsorption involves more than RBP alone. Both strains make aberrant baseplates that appear to lack both FibC and RBP. FibO may pl...

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The Floating (Pathogenicity) Island: A Genomic Dessert

Cited by 60 publications

References 64 publications

Understanding the Streptococcus mutans Cid/Lrg System through CidB Function

Understanding the Streptococcus mutans Cid/Lrg System through CidB Function

Staphylococcal pathogenicity islands — movers and shakers in the genomic firmament

Structure and Function of the Staphylococcus aureus Bacteriophage 80α Baseplate

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