Abstract
Until 2007, Staphylococcus aureus from clonal complex 398 (CC398) was exclusively associated with livestock species and companion animals. Recently, several studies described the emergence of S. aureus CC398 as etiologies of severe infections in humans living in an animal-free environment. Recent sequencing efforts showed that the mobile genetic elements found in CC398 isolates were specific for each population and enabled differentiation of strains responsible for asymptomatic colonization from strains involved in bloodstream infections. We mobilized prophages from a human CC398 isolate and introduced them into two naïve ancestral isolates devoid of prophages that exclusively colonize animals. These lysogenized ancestral CC398 isolates acquired features related to virulence, such as an increased capacity to adhere to human extracellular matrix proteins and the ability to invade and survive within non-phagocytic cells. Pathogenicity of several clinical isolates from the CC398 lineage as well as ancestral and in vitro lysogenized ancestral counterparts was assessed in a model of infectious endocarditis in rats. Natural and artificial lysogens were not only more invasive than their prophage-free parent but also showed an increased capacity to multiply within aortic vegetations. This study identified prophages as mediators of bacterial virulence in a model of infectious endocarditis, probably through promotion of interaction with extracellular matrix components. Further studies are needed to identify mechanisms leading to promotion of intrinsic virulence.
Highlights
Challenges related to Staphylococcus aureus infections in the human and veterinary clinics mobilized important human and technical resources
S1 was identified from a pig farmer and its genome sequence revealed the presence of two prophages (Diene et al, 2017), namely 2Pro and 3Pro
The genome sequence of S123Sa2 -a strain lysogenized with prophages mobilized from S1- showed that the two prophages from S1 are integrated at the same locations they occupied in the S1 parental strain; this was an intergenic region between tmRNA and a hypothetical protein for phage 3Pro and in ecsB for phage 2Pro. tmRNA was not disrupted and no difference in strain pigmentation was observed
Summary
Challenges related to Staphylococcus aureus infections in the human and veterinary clinics mobilized important human and technical resources. S. aureus can colonize 20–30% of the general population asymptomatically but is capable of causing a wide spectrum of diseases ranging from benign infections, to severe diseases such as endocarditis, necrotizing pneumonia, osteomyelitis, or septicemia (Lowy, 1998; Lew and Waldvogel, 2004). The role of some major staphylococcal adhesins has been described in vitro and in experimental models of infections (McDevitt et al, 1994; Patti et al, 1994; Entenza et al, 2000; Elasri et al, 2002). Immune escape and the ability to form biofilms are important characteristics of S. aureus pathogenesis and persistence of colonization and infection (Costerton et al, 1999)
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