Methicillin-Susceptible ST398 Staphylococcus aureus Responsible for Bloodstream Infections: An Emerging Human-Adapted Subclone?

Abstract

In the course of an annual 3-month bloodstream infections (BSI) survey conducted during a four-year period in 31 healthcare institutions located in three noncontiguous French regions, we report 18 ST398 Staphylococcus aureus BSI. ST398 BSI incidence showed a seven-fold increase during the study period (0.002 per 1,000 patient days in 2007 vs. 0.014 in 2010). ST398 BSI isolates differed from the pig-borne multiresistant clone: 17/18 BSI isolates were methicillin susceptible and none was of t011, t034 or t108 pig-borne spa-types. ST398 BSI isolates had homogenous resistance patterns (15/18 with only Eryr) and prophagic content (all harboured the hlb-converting Sau3int phage). The clustering of BSI and pig-borne isolates by spa-typing and MLVA, the occurrence of Sau3int phage in BSI isolates and the lack of this phage in pig-borne isolates suggest that the emergence of BSI isolates could have arisen from horizontal transfer, at least of the Sau3int phage, in genetically diverse MSSA ST398 isolates. The acquisition of the phage likely plays a role in the increasing ability of the lysogenic ST398 isolates to colonize human. The mode of acquisition of the non pig-borne ST398 isolates by our 18 patients remains unclear. ST398 BSI were diagnosed in patients lacking livestock exposure and were significantly associated with digestive portals of entry (3/18 [16.7%] for ST398 vs. 19/767 [2.5%] for non ST398 BSI; p = .012). This raises the question of possible foodborne human infections. We suggest the need for active surveillance to study and control the spread of this human-adapted subclone increasingly isolated in the hospital setting.

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

“…Twenty-one CC398 isolates were studied (Table 1), comprising two populations of isolates: (i) ten isolates representative of the diversity of the LA clade, including nine Dutch and one French isolates, recovered from humans (n = 4) or animals (n = 6), and belonging to the major spa-types t899 (n = 2), t011 (n = 2), t034 (n = 2), t571 (n = 2) and t108 (n = 2); (ii) eleven isolates recovered over a four-year period in three geographically separated French regions (Valentin-Domelier et al, 2011) from patients with no LA risk factors and diagnosed with bloodstream infections (n = 10) or urinary tract infection (n = 1). These isolates belonged to six different spa-types: t899 (n = 1), t1451 (n = 2), t571 (n = 5), t6605 (n = 1), t5635 (n = 1) and t9378 (n = 1).…”

“…Originally detected in pig farmers in Europe (Witte et al, 2007), Staphylococcus aureus belonging to CC398 has become a worldwide threat associated with livestock, their human contacts and food products (van Belkum et al, 2008). Microarrays and whole-genome sequencing approaches applied to a large number of CC398 isolates distinguished two clades within the CC398 lineage (Price et al, 2012;Uhleman et al, 2012;McCarthy et al, 2011): the classical LA clade, isolates of which have long been responsible for frequent and transient colonization, and rare infections, of farmers and veterinarians (Huijsdens et al, 2006); and a human clade.…”

“…Microarrays and whole-genome sequencing approaches applied to a large number of CC398 isolates distinguished two clades within the CC398 lineage (Price et al, 2012;Uhleman et al, 2012;McCarthy et al, 2011): the classical LA clade, isolates of which have long been responsible for frequent and transient colonization, and rare infections, of farmers and veterinarians (Huijsdens et al, 2006); and a human clade. This human clade is comprised of two subpopulations: the ancestral human subpopulation, and the emerging human-adapted non-LA CC398 subpopulation that has recently and increasingly been causing invasive infections worldwide in humans living in animal-free environments (Price et al, 2012;Valentin-Domelier et al, 2011;Jimenez et al, 2011;Stegger et al, 2010), and that readily colonize and spread between humans (Uhleman et al, 2012).…”

Messages from the first International Conference on Clinical Metagenomics (ICCMg)

“…Most isolates were spa-type t571 or t1451 (50.7 and 30.4%, respectively); the MRSA isolate was spa-type t899. For comparative analysis, we used five ST398 animal-associated isolates representative of the isolates colonizing and infecting animals described in previous studies [6,7,[12][13][14][15], and the animalassociated MRSA isolate s0385, which was responsible for a human case of endocarditis [16].…”

“…Evidence for two major evolutionary changes in the ST398 lineage was recently provided by studies conducted worldwide [3][4][5][6][7][8][9]. First, there has been a widening of the infection spectrum of these bacteria to include humans living in animal-free environments and companion and livestock animals other than pigs.…”