Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59

Abstract

Understanding virulence is vital for the development of novel therapeutics to target infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which cause an ongoing epidemic in the United States and are on a global rise. However, what defines virulence particularly of global CA-MRSA lineages is poorly understood. Threatening a vast population, the predominant Asian CA-MRSA lineage ST59 is of major epidemiological importance. However, there have been no molecular analyses using defined virulence gene deletion mutants in that lineage as of yet. Here, we compared virulence in skin, lung, and blood infection models of ST59 CA-MRSA isolates with geographically matched hospital-associated MRSA isolates. We selected a representative ST59 CA-MRSA isolate based on toxin expression and virulence characteristics, and produced isogenic gene deletion mutants of important CA-MRSA virulence determinants (α-toxin, PSM α, Agr) in that isolate for in-vitro and in-vivo analyses. Our results demonstrate strongly enhanced virulence of ST59 CA-MRSA over hospital-associated lineages, supporting the notion that enhanced virulence is characteristic for CA-MRSA. Furthermore, they show strong and significant contribution of Agr, α-toxin, and PSMα to pathogenesis of ST59 CA-MRSA skin, lung, and blood infection, emphasizing the value of drug development efforts targeted toward those virulence determinants.

Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution

“…Remarkably, most (six of eight) of the ST398 CA-MRSA infection cases were severe (i.e., invasive) and two were fatal. These numbers, although too small for a statistically meaningful comparison, are exceptionally high, for example, when comparing to data we previously assembled for ST59 CA-MRSA in the same region [ 26 ], and emphasize the high virulence potential of the ST398 isolates (Tables 2 and 3 ).…”

“…In addition, two USA300 CA-MRSA strains (SF8300, LAC) and the genome-sequenced LA-MRSA S0385 standard strain were used in the comparisons. Isolate selection for the MSSA and HA-MRSA groups was performed, as in a previous study [ 26 ], by selecting isolates whose average PSM production was similar to that of the entire group and thus reflects the average virulence potential. Notably, for the in vivo infection studies, the ST398 CA-MRSA, MSSA, and ST5/ST239 HA-MRSA isolates were obtained from the corresponding type of human infection (respiratory and skin infection, respectively).…”

Molecular Characteristic and Virulence Gene Profiles of Community-Associated Methicillin-Resistant Staphylococcus aureus Isolates from Pediatric Patients in Shanghai, China

“…During recent years, CA-MRSA infections have been found worldwide and the major pandemic clones are usually related to specific geographical locations (Mediavilla et al, 2012; Li et al, 2016). For instance, the ST1 and ST8 clone in the USA and Canada, the ST30 clone in Australia, the ST80 clone in Europe, the ST59 clone in the Asia-Pacific region, including Taiwan and Australia.…”

Phylogenetic analysis and virulence determinant of the host-adapted Staphylococcus aureus lineage ST188 in China

“…The dominant CA-SA strain in the United States is the highly virulent USA300 (ST8), while the predominant Asian CA-SA lineage is ST59 11 . ST59 exhibits more pronounced virulence than the geographically matched HA-MRSA clones ST5 and ST239 12 . By high expression of core genome-encoded virulence determinants, CA-SA has acquired high-virulence phenotypes 13 .…”