The Staphylococci phages family: an overview

Abstract

Due to their crucial role in pathogenesis and virulence, phages of Staphylococcus aureus have been extensively studied. Most of them encode and disseminate potent staphylococcal virulence factors. In addition, their movements contribute to the extraordinary versatility and adaptability of this prominent pathogen by improving genome plasticity. In addition to S. aureus, phages from coagulase-negative Staphylococci (CoNS) are gaining increasing interest. Some of these species, such as S. epidermidis, cause nosocomial infections and are therefore problematic for public health. This review provides an overview of the staphylococcal phages family extended to CoNS phages. At the morphological level, all these phages characterized so far belong to the Caudovirales order and are mainly temperate Siphoviridae. At the molecular level, comparative genomics revealed an extensive mosaicism, with genes organized into functional modules that are frequently exchanged between phages. Evolutionary relationships within this family, as well as with other families, have been highlighted. All these aspects are of crucial importance for our understanding of evolution and emergence of pathogens among bacterial species such as Staphylococci.

Figure 1

Modular organization of Staphylococci phages genomes (a) Siphoviridae genomes. Colored boxes represent the five functional modules found in Siphoviridae genomes. Red: lysogeny, yellow: DNA metabolism, green: DNA packaging and capsid morphogenesis, blue: tail morphogenesis, pink: cell host lysis. Virulence genes (purple) are generally found downstream the lysis module, or inserted between the lysogeny and DNA metabolism module. A closer view of the DNA packaging and capsid morphogenesis shows the structural genes pattern typical of the Sfi21- and Sfi11- like phages genera (see text for details); (b) Podoviridae genomes. Lysis module (pink) and tail morphogenesis modules (blue) are overlapping. DNA metabolism genes (i.e., single-strand DNA binding protein and DNA polymerase; green) are located in a region of genes of unknown function (gray), upstream to the tail module. An encapsidation protein is encoded next to the DNA polymerase in the staphylococcal Podoviridae genomes described so far. (c) Myoviridae genomes. The phage Twort genome is represented as an example. A large region encodes genes of unknown function (gray). DNA metabolism genes (yellow) are distributed in two distinct modules (known as replication modules), as well as lysis genes (pink) that are found upstream and downstream to DNA packaging and capsid (green) and tail modules (blue). TerS: small subunit terminase, TerL: large subunit terminase, Port: portal protein, Prot: protease, MHP: major capsid protein, H: capsid morphogenesis protein, mHP: minor capsid protein, SS-DNA binding: single strand DNA binding protein.

Figure 2

Network representation of relationships between Staphylococci phages based on protein content (adapted from [37]). Circles represent the nine different clusters defined by Markov cluster algorithm (MCL). The color indicates the host species (magenta: S. aureus; purple: S. aureus and CoNS; blue: CoNS). The number of genomes is indicated into brackets. Cluster 8 corresponds to the class I (Podoviridae), clusters 1–6 and 9 to class II (Siphoviridae) and cluster 7 to class III (Myoviridae). Cluster 1 corresponds to clade A, cluster 4 to clade B, and clades C and D were split into two sub-clades (clusters 2 and 3, and 5 and 6, respectively). Cluster 9 constitutes a new clade. In this schematic representation, gray lines between distinct clusters indicate that at least 30% of homologous proteins are shared between at least two phage genomes. Following this analysis, two previously unclassified phages (2638A and 187) were included in cluster 6 and 1, respectively. PT1028 was not included in this analysis.