Diversity of Prophages in Dominant Staphylococcus aureus Clonal Lineages

Abstract

Temperate bacteriophages play an important role in the pathogenicity of Staphylococcus aureus, for instance, by mediating the horizontal gene transfer of virulence factors. Here we established a classification scheme for staphylococcal prophages of the major Siphoviridae family based on integrase gene polymorphism. Seventy-one published genome sequences of staphylococcal phages were clustered into distinct integrase groups which were related to the chromosomal integration site and to the encoded virulence gene content. Analysis of three marker modules (lysogeny, tail, and lysis) for phage functional units revealed that these phages exhibit different degrees of genome mosaicism. The prevalence of prophages in a representative S. aureus strain collection consisting of 386 isolates of diverse origin was determined. By linking the phage content to dominant S. aureus clonal complexes we could show that the distribution of bacteriophages varied remarkably between lineages, indicating restriction-based barriers. A comparison of colonizing and invasive S. aureus strain populations revealed that hlb-converting phages were significantly more frequent in colonizing strains.Staphylococcus aureus asymptomatically colonizes the anterior nares of humans but also causes a wide spectrum of acute and chronic diseases. Most of the dissimilarity between S. aureus strains is due to the presence of mobile genetic elements such as plasmids, bacteriophages, pathogenicity islands, transposons, and insertion sequences (2,14,19,23). Many virulence factors are encoded on such mobile elements (3,6,17,26,27,35). In particular, bacteriophages play an important role in the pathogenicity of S. aureus either by carrying accessory virulence factors such as Panton-Valentine leukocidin (PVL) (encoded by the luk-PV operon), staphylokinase (encoded by sak), enterotoxin A (encoded by sea), and exfoliative toxin A (encoded by eta) or by interrupting chromosomal virulence genes such as those for ␤-hemolysin (hlb) and lipase (geh) upon insertion. Additionally, phages are the primary vehicle of lateral gene transfer between S. aureus strains, providing the species with the potential for broad genetic variation. We could show that phages increase the genome plasticity of S. aureus during infection, facilitating the adaptation of the pathogen to various host conditions (11,12).Despite the obvious importance of phages for the biology of S. aureus, epidemiological data on the prevalence of phages in this species are limited (28, 33). More than 80 genome sequences of staphylococcal bacteriophages and prophages are available in the public genome databases. Most published S. aureus phages belong to the Siphoviridae family of temperate, tailed bacterial viruses. Traditionally, S. aureus phages were characterized according to their lytic activity, morphology, and serological properties (1, 28). Today, the temperate phages in clinical S. aureus isolates can by identified with a multiplex PCR strategy, which is based on sequence differences between viral genes codin...

Analysis of prophages harbored by the human-adapted subpopulation of Staphylococcus aureus CC398

“…Lysogeny is a symbiotic strategy in which the prophage has a stable niche in the host genome, and protects its host against attack by other phages (Goerke et al, 2009), through co-immunity, CRISPR interference (Barrangou et al, 2007;Marraffini and Sontheimer, 2008) or expression of RM activities that inhibit interspecies and even intraspecies gene transfers (Barrangou et al, 2007;Park et al, 1999). This may be particularly relevant for the CC398 lineage.…”

“…S. aureus is highly lysogenic. S. aureus phages are double-stranded DNA phages belonging to the Siphoviridae family (Goerke et al, 2009). Comparative genomic analyses have revealed substantial diversity of these phages; nevertheless, they also display extensive mosaicism, with genes organized into functional modules that are frequently exchanged between phages (Kahankova et al, 2010;Xia and Wolz, 2013).…”

“…Some carry genes encoding diverse virulence factors including panton-valentine leukocidin, staphylokinase, enterotoxins, chemotaxis-inhibitory proteins, and exfoliative toxins. Other phages have inserted into and consequently interrupt chromosomal virulence genes such as those for b-hemolysin (hlb) and lipase (geh) (Goerke et al, 2009).…”

Two novel temperate bacteriophages co-existing in Aeromonas sp. ARM81 – characterization of their genomes, proteomes and DNA methyltransferases

“…Genome analyses of many genera, such as Bacillus, Enterococcus, Listeria, Mannheimia, Paracoccus, Staphylococcus and Streptococcus revealed that polylysogeny is a common phenomenon (Dziewit et al, 2014a;Goerke et al, 2009;Niu et al, 2015). Recently, we have also identified a polylysogenic Sinorhizobium sp.…”

Therapeutic Potential of Staphylococcal Bacteriophages for Nasal Decolonization of <i>Staphylococcus aureus</i> in Mice

“…Although temperate phages of S. aureus are more widely known [53,54], due to the potential problems of lysogeny and toxic gene transfer, its therapeutic use is limited [55]. Hence, the present article on efficacy of two lytic bacteriophages of staphylococcus namely Phage K and 44AHJD on nasal decolonization of Staphylococcus aureus in mice nares is relevant and valuable.…”