title: Impact of bacteriophage Saint3 carriage on the immune evasion capacity and hemolytic potential of Staphylococcus aureus CC398.
abstract: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates of clonal complex 398 (CC398) are frequently found in Europe, and recent studies highlighted the importance of mobile genetic element (MGE) exchange for host adaptation of this lineage. Of note, one of the MGEs commonly found in human S. aureus isolates, the immune evasion cluster (IEC) harboring bacteriophage Saint3, is very rarely found in LA-MRSA CC398 isolates obtained from farm animals, but more frequently found in LA-MRSA CC398 that were retransmitted to humans. Here, we analyzed with a set of S. aureus CC398 isolates harboring/lacking φSaint3 how this MGE affects (i) phagocytosis of CC398 isolates by polymorphonuclear neutrophils (PMNs), and (ii) hemolysis of human and livestock-derived erythrocytes. Isolates lacking φSaint3 were more efficiently phagocytosed by human PMNs in whole blood phagocytosis assays than isolates harboring this bacteriophage, irrespective of their origin. Notably, a similar effect was observed when equine blood was utilized, but not detected with porcine blood. Integration of φSaint3 into LA-MRSA CC398 strains lacking this MGE confirmed these findings, as φSaint3-harboring recipients were again less efficiently ingested by PMNs in equine and human blood than their parental strains. Integration of φSaint3 strongly reduced the hemolytic potential of the culture supernatants against human-derived erythrocytes, and to a smaller extent also against porcine-derived erythrocytes, while φSaint3 integration only slightly affected the hemolytic capacities against equine-derived red blood cells. The significant protective effect of φSaint3 against phagocytosis by equine PMNs suggests that the host specificity of the IEC components might be broader than currently assumed.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Saarland, Homburg, Germany. Electronic address: philipp.jung@uks.eu.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jung
authors.affiliation: Robert Koch Institute, Wernigerode, Germany; Service of Hospital Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Mohamed M H
authors.initials: MM
authors.lastname: Abdelbary
authors.affiliation: Federal Institute for Risk Assessment (BfR), Berlin, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Kraushaar
authors.affiliation: Federal Institute for Risk Assessment (BfR), Berlin, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fetsch
authors.affiliation: Clinical Chemistry and Laboratory Medicine/Central Laboratory, University Hospital of Saarland, Homburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Saarland, Homburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Robert Koch Institute, Wernigerode, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Witte
authors.affiliation: Robert Koch Institute, Wernigerode, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Cuny
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Saarland, Homburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics*; D001435:Bacteriophages / Q000502:physiology*; D004912:Erythrocytes / Q000382:microbiology; D006460:Hemolysin Proteins / Q000235:genetics*; D006461:Hemolysis; D006736:Horses; D058507:Host Specificity; D006801:Humans; D057131:Immune Evasion; D058751:Livestock; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000276:immunology / Q000821:virology*; D009504:Neutrophils; D010587:Phagocytosis; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology*; D013552:Swine
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus
keywords: CC398; Immune evasion cluster; Phagocytosis; Staphylococcus aureus; β-Hemolysin; φSaint3