The vast majority of bacteria contain prophages, either integrated into their chromosome or as extra-chromosomal elements, accounting for substantial genetic variability. Not only do phages shape bacterial genome architecture, they also constitute major vehicles for horizontal gene transfer [1
]. In addition, they contribute to virulence by encoding numerous virulence or fitness factors and by their movements within genomes (see below, Section 2.2
]. These mobile elements are responsible for gene disruption, provide anchor region for genomic rearrangements, protect bacteria from lytic infections or, in contrast, provoke cell lysis through prophage induction [2
]. Thus, phages play essential roles in bacterial evolution and adaptation.
Phages are widespread in Staphylococcus aureus
and have been extensively studied [1
]. They were firstly used for the typing of clinical S. aureus
]. S. aureus
is a major human and animal pathogen that causes both nosocomial and community-acquired infections. It colonizes skin and mucous membranes, with the anterior nares being the primary niche in humans. While found in healthy carriers, S. aureus
is also responsible for a wide range of diseases, from mild skin infections to severe life-threatening infections, such as sepsis or endocarditis [6
]. The number of prophages in S. aureus
genome is generally high. All S. aureus
genome sequenced so far do contain at least one prophage, and many strains carry up to four [1
]. These encode numerous staphylococcal toxins responsible for pathogenesis [1
also comprise coagulase-negative species (coagulase-negative Staphylococci
, CoNS), which are distinguishable from S. aureus
by the lack of coagulase-encoding gene. In contrast to S. aureus
, which is only found in part of the population, these species belong to the commensal flora of healthy humans. Some species are associated to specific niches, and others appear to be more ‘generalist’ and are generally found on the body surface [9
]. CoNS include human opportunistic pathogens often associated with medical devices. S. epidermidis
is referred to as a frequent cause of nosocomial infections [9
]. In addition, ‘true’ pathogens that are not associated with medical devices may also be problematic for public health. As an example, S. saprophyticus
is considered as a frequent pathogen responsible for uncomplicated urinary tract infections [11
]. Pathogenesis of CoNS species relies on factors required for their commensal mode of life or fitness (e.g. factors involved in adhesion, in biofilm formation and in persistence) and not on toxins, as observed for S. aureus
]. As a consequence, less attention has been paid to these phages.
During the past decade, sequencing of Staphylococci
genomes and extensive comparative genomic analyses have significantly increased the number of staphylococcal phages identified. Up to now, more than 68 Staphylococci
phages and prophages sequences, mainly from S. aureus
, are found in the [14
]. In addition, 268 Staphylococci
genomes are available on the PATRIC server [15
] and offer a remarkable source of novel prophage sequences for further studies (see below).
In this review, we provide an overview of Staphylococci phages with a focus on their contribution to pathogenesis. A special interest is placed on the classification methods, as well as on the evolutionary relationships connecting staphylococcal phages. Phage classification is often problematic, due to the modular organization of phage genomes. Relationships between Staphylococci phages and phages from other species are also discussed in an evolutionary perspective. Finally, the potential use of staphylococcal phages for bio-technological and medical applications is briefly addressed.