Available online 6 December 2021, 151545

Genome of S. aureus SG511-Berlin, a screening strain for antibiotic lead structures

Strain is hyper-susceptible towards cell wall and membrane targeting agents

Genome displays a lack of mobile elements when compared to S. aureus MRSA252

Amino acid substitutions identified in CodY, SarZ, TcaR, SaeR, GdpP, and Rny

Truncation of ebh, inactivation of graS, and agrC, as well as loss of spa and sarS

The genetic plasticity of Staphylococcus aureus has facilitated the evolution of many virulent and drug-resistant strains. Here we present the sequence of the 2.74 Mbp genome of S. aureus SG511-Berlin, which is frequently used for antibiotic screening. Although S. aureus SG511 and the related methicillin-resistant S. aureus MRSA252 share a high similarity in their core genomes, indicated by an average nucleotide identity (ANI) of 99.83%, the accessory genomes of these strains differed, as nearly no mobile elements and resistance determinants were identified in the genome of S. aureus SG511. Susceptibility testing showed that S. aureus SG511 was susceptible to most of the tested antibiotics of different classes. Intriguingly, and in contrast to the standard laboratory strain S. aureus HG001, S. aureus SG511 was even hyper-susceptible towards cell wall and membrane targeting agents, with the exception of the MurA-inhibitor fosfomycin. In depth comparative genome analysis revealed that, in addition to the loss of function mutation in the antibiotic sensor histidine kinase gene graS, further mutations had occurred in the lysyltransferase gene mprF, the structural giant protein gene ebh, and the regulator genes codY and saeR, which might contribute to antibiotic susceptibility. In addition, an insertion element in agrC abolishes Agr-activity in S. aureus SG511, and the spa and sarS genes, which encode the surface protein SpA and its transcriptional regulator, were deleted. Thus, the lack of mobile resistance genes together with multiple mutations affecting cell envelope morphology may render S. aureus SG511 hyper-susceptible towards most cell wall targeting agents.

Staphylococcus aureus SG511

graRS

Genome

Antibiotic susceptibility

MRSA252

HG001

© 2021 The Author(s). Published by Elsevier GmbH.