Wild type agr-negative livestock-associated MRSA exhibits high adhesive capacity to human and porcine cells

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of nosocomial infections and a major public health concern worldwide. During the last decade, MRSA of CC398 have emerged as important colonizers of livestock. These strains also represent an increasing cause of human infections. A recent study reporting a new dominant spa type among MRSA from Finish fattening pigs (CC398/t2741) identified a strain lacking both the global virulence regulator gene locus agr and the adhesion gene fnbB. The aim of this study was to characterize this agr/fnbB-negative livestock-associated MRSA strain in terms of growth, hemolysis and adhesive capacity, and to provide data on its genomic background. To this end, growth curves and hemolysis patterns were generated and adhesion assays on human keratinocyte and porcine nasal mucosa cell lines were performed. Whole genome sequencing was used to determine the nature and extent of the relevant deletions in the livestock strains. For comparison, an agr-positive, fnbB-negative CC398/t2741 strain from the same pig herd, an agr/fnbB- positive CC398/t034 strain from another pig herd and one human MRSA strain and its isogenic Δagr knockout mutant were used. The agr-negative strains adhered significantly better to human and porcine host cells than the agr-positive control strains. For the agr-positive porcine MRSA strains, cytotoxic effects on porcine mucosal cells were observed. The strong adhesive capacity of the naturally agr-negative livestock-associated MRSA, in combination with diminished cytotoxic effects, is likely favorable for inducing persistent colonization in pigs. Independently of the host cell type, similar adhesive capacities of the naturally agr-negative livestock-associated MRSA and the human MRSA strain were shown. Our results indicate that loss of agr in the livestock-associated MRSA strain investigated in this study may have increased its potential to be transmitted to and amongst humans.