Abstract
BackgroundLivestock-associated (LA)-CC398-MRSA is closely related to pigs, being unfrequently detected in human invasive infections. CC398-MSSA is emerging in human invasive infections in some countries, but genetic and epidemiological characteristics are still scarcely reported.ObjectivesTo determine the prevalence of Staphylococcus aureus (SA) CC398, both MRSA and MSSA, among blood cultures SA isolates recovered in Spanish hospitals located in regions with different pig-farming densities (PD) and characterize the recovered isolates.MethodsOne thousand twenty-two SA isolates (761 MSSA, 261 MRSA) recovered from blood cultures during 6–12 months in 17 Spanish hospitals (2018–2019) were studied. CC398 lineage identification, detection of spa-types, and antibiotic resistance, virulence and human immune evasion cluster (IEC) genes were analyzed by PCR/sequencing.ResultsForty-four CC398-MSSA isolates (4.3% of SA; 5.8% of MSSA) and 10 CC398-MRSA isolates (1% of SA; 3.8% of MRSA) were detected. Eleven spa-types were found among the CC398-MSSA isolates with t571 and t1451 the most frequent spa-types detected (75%). Most of CC398-MSSA isolates were Immune-Evasion-Cluster (IEC)-positive (88.6%), tetracycline-susceptible (95.5%) and erythromycin/clindamycin–inducible-resistant/erm(T)-positive (75%). No statistical significance was detected when the CC398-MSSA/MSSA rate was correlated to PD (pigs/km2) (p = 0.108). On the contrary, CC398-MRSA isolates were all IEC-negative, predominately spa-t011 (70%), and the CC398-MRSA/MRSA rate was significantly associated to PD (p < 0.005).ConclusionCC398-MSSA is an emerging clade in invasive infections in Spanish hospitals. CC398-MRSA (mostly t011) and CC398-MSSA (mostly t571 and t1451) show important differences, possibly suggesting divergent steps in host-adaptation evolutionary processes. While CC398-MRSA is livestock-associated (lacking IEC-system), CC398-MSSA seems to be mostly livestock-independent, carrying human-adaptation markers.
Highlights
Livestock-associated (LA) methicillin-resistant S. aureus (MRSA) of clonal complex (CC) 398 has gained much attention during the past decade because, apart from colonizing farm-animals, it has become a frequent pathogen in humans mainly -but not always- in contact with livestock (Lozano et al, 2012; Benito et al, 2014; Becker et al, 2017; Murra et al, 2019)
The lineage CC398 was detected in this multicenter study in 5.3% of total S. aureus isolates (Table 1)
The distribution among the hospitals was heterogenous in our study, with slight differences observed in the prevalence of CC398-methicillin-susceptible S. aureus (MSSA)/MSSA when hospitals of very high pig density (VHPD), HPD, MPD, and LPD regions were compared; no statistical significance was detected when the CC398-MSSA /MSSA rate was correlated to PD (p = 0.108)
Summary
Livestock-associated (LA) methicillin-resistant S. aureus (MRSA) of clonal complex (CC) 398 has gained much attention during the past decade because, apart from colonizing farm-animals, it has become a frequent pathogen in humans mainly -but not always- in contact with livestock (Lozano et al, 2012; Benito et al, 2014; Becker et al, 2017; Murra et al, 2019). Based on whole genome sequencing analysis, LA-CC398MRSA has evolved from an ancestor human-adapted (HA) methicillin susceptible S. aureus (MSSA) CC398 (Price et al, 2012). This CC398-MSSA would have acquired methicillin and tetracycline resistance and lost the prophage Sa3, that carries the immune evasion cluster (IEC) genes; IEC is a set of genes which protects S. aureus against the human immune system (Van Wamel et al, 2006). A subpopulation of CC398-MSSA carrying the IEC system seems to be emerging in human infections, as previously indicated, in patients without livestock exposure, that could have evolved from the HA-MSSA ancestor (Bouiller et al, 2020). CC398-MSSA is emerging in human invasive infections in some countries, but genetic and epidemiological characteristics are still scarcely reported
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