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Published on: February 19, 2019
Prophages of Staphylococcus aureus Newman and their contribution to virulence
Taeok Bae1, Tadashi Baba, Keiichi Hiramatsu
1Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.
Abstract:
Four prophages (phiNM1-4) were identified in the genome of Staphylococcus aureus Newman, a human clinical isolate. phiNM1, phiNM2 and phiNM4, members of the siphoviridae family, insert at different sites (poiA, downstream of isdB and geh) in the staphylococcal chromosome. phiNM3, a beta-haemolysin (hlb) converting phage, encodes modulators of innate immune responses (sea, sak, chp and scn) in addition to other virulence genes. Replication of phiNM1, phiNM2 and phiNM4 occurs in culture and during animal infection, whereas phiNM3 prophage replication was not observed. Prophages were excised from the chromosome and S. aureus variants lacking phiNM3 or phiNM1, phiNM2 and phiNM4 displayed organ specific virulence defects in a murine model of abscess formation. S. aureus Newman lacking all four prophages was unable to cause disease, thereby revealing essential contributions of prophages to the pathogenesis of staphylococcal infections.
Insights
Staphylococcus aureus prophages are essential for causing disease. Deleting these phages significantly reduces virulence, highlighting their critical role in staphylococcal infections.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Staphylococcus aureus is a significant human pathogen.
- Bacteriophages, specifically prophages, can integrate into bacterial genomes and influence host traits.
- The role of multiple prophages in S. aureus pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the contribution of four identified prophages (phiNM1-4) in the Staphylococcus aureus Newman strain to bacterial pathogenesis.
- To determine the impact of individual and combined prophage deletions on S. aureus virulence.
Main Methods:
- Identification and characterization of four prophages (phiNM1-4) within the S. aureus Newman genome.
- Genetic manipulation to create S. aureus variants lacking specific prophages (phiNM3 or phiNM1, phiNM2, phiNM4).
- Assessment of bacterial virulence using a murine model of abscess formation.
Main Results:
- phiNM1, phiNM2, and phiNM4 (Siphoviridae family) insert at distinct chromosomal locations.
- phiNM3 encodes beta-haemolysin (hlb) and virulence factors modulating innate immunity (sea, sak, chp, scn).
- Prophage excision and deletion mutants exhibited organ-specific virulence defects in vivo; complete prophage removal abolished disease causation.
Conclusions:
- Prophages phiNM1-4 play essential roles in the pathogenesis of Staphylococcus aureus infections.
- The absence of these prophages leads to significant attenuation of virulence.
- Prophages are critical determinants of S. aureus disease development.
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