Human Infection of Methicillin-Susceptible Staphylococcus aureus CC398: A Review

Abstract

Staphylococcus aureus (SA) belonging to the clonal complex 398 (CC398) took a special place within the species due to its spread throughout the world. SA CC398 is broadly separated in two subpopulations: livestock-associated methicillin-resistant SA (MRSA) and human-associated methicillin-susceptible SA (MSSA). Here, we reviewed the global epidemiology of SA CC398 in human clinical infections and focused on MSSA CC398. The last common ancestor of SA CC398 was probably a human-adapted prophage φSa3-positive MSSA CC398 strain, but the multiple transmissions between human and animal made its evolution complex. MSSA and MRSA CC398 had different geographical evolutions. Although MSSA was present in several countries all over the world, it was mainly reported in China and in France with a prevalence about 20%. MSSA CC398 was frequently implicated in severe infections such as bloodstream infections, endocarditis, and bone joint infections whereas MRSA CC398 was mainly reported in skin and soft tissue. The spread of the MSSA CC398 clone is worldwide but with a heterogeneous prevalence. The prophage φSa3 played a crucial role in the adaptation to the human niche and in the virulence of MSSA CC398. However, the biological features that allowed the recent spread of this lineage are still far from being fully understood.

Keywords: CC398; ST398; blood stream infection; methicillin-susceptible Staphylococcus aureus.

Figure 1

Schematic representation of the evolution of different subpopulations within the CC398 lineage. The last common ancestor of Staphylococcus aureus (SA) CC398 was probably a human-adapted immune evasion cluster (IEC)-positive methicillin-susceptible SA (MSSA) CC398 strain, which at a later stage acquired SCCmec, leading to the emergence of human methicillin-resistant SA (MRSA) CC398 strains. At some point, the ancestral MSSA CC398 strain jumped to livestock, which was accompanied by the loss of IEC and the acquisition of tet(M), conferring resistance to tetracycline and later on by the acquisition of SCCmec, conferring resistance to methicillin, leading to the emergence of livestock-associated MRSA CC398. However, Ward et al. [14] supported the existence of distinct human- and livestock-associated clades that emerged at similar times, which was represented by “?*” in the figure. Because some interspecies transmission in both directions was described, a double-arrow was used to represent the different livestock-associated clade subpopulations. These transmissions were probably responsible for the acquisition of the prophage φSa3 in the LA clade, which differentiated human (Hu) SA CC398 subpopulations from the adapted Humans (HuA) livestock-associated (LA) SA CC398 subpopulations.

Figure 2

Number of MRSA (A,B) and MSSA (C,D) CC398 isolates from clinical infection in the world and in Europe. MRSA: Denmark (n = 1727), Germany (n = 600), The Netherlands (n = 446), Spain (n = 310), China (n = 78), Belgium (n = 77), Austria (n = 67), Sweden (n = 2), Slovenia (n = 6), France (n = 18), Luxembourg (n = 16), United Kingdom (n = 14), Hungary (n = 12), Finland (n = 10), New Zealand (n = 7), Italy (n = 6), Greece (n = 4), Canada (n = 4), United States (n = 3), Japan (n = 2), Hong Kong (n = 2) Laos (n = 1), Japan (n = 1), Australia (n = 1), Norway (n = 1), Ireland (n = 1), Poland (n = 1); MSSA: France (n = 711), China (n = 255), United States (n = 117), Belgium (n = 58), Portugal (n = 18), Greece (n = 17), The Netherlands (n = 7), Dominican Republic (n = 7), Iran (n = 6), Germany (n = 6), Spain (n = 4), Denmark (n = 4), Laos (n = 4), Ireland (n = 2), Colombia (n = 2), Italy (n = 1), Ecuador (n = 1), Brazil (n = 1).