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Published on: February 19, 2019
A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune
Roshan Nepal1,2,3, Ghais Houtak1,2, George Bouras1,2
1The Faculty of Health and Medical Sciences The University of Adelaide Adelaide Australia.
Abstract:
Staphylococcus aureus with varying virulence is often isolated from chronic rhinosinusitis (CRS) patients and impacts disease severity. Prophage-mediated virulence, particularly encoded by φSa3int (NM3) prophages, which often encodes human immune-evasion cluster genes is well known, but how a new prophage domestication impacts overall expression of core bacterial genes, and the expression of resident prophages is understudied. To understand this, we transduced a φSa3int prophage recovered from hyper-biofilm forming mucoid S. aureus (SA333) into a high-biofilm forming non-mucoid S. aureus (SA222) recovered from same CRS patient but at different time points. Upon φSa3int prophage domestication, we observed a significant upregulation of 21 exoproteins including human immune-evasion toxins and an intercellular adhesion protein B (IcaB). Further, φSa3int prophage domestication led to reduced phagocytosis implying φSa3int prophage mediates escape of S. aureus from human innate immunity. Our data further show that in addition to adding novel prophage-encoded virulence, φSa3int prophage domestication also affects the expression of non-prophage (bacterial) genes and suppresses expression of structural proteins of resident prophages. Since strains without prophage or with specific prophages have varying virulence and pathogenicity, targeted identification virulence factors associated with mobile genetic elements (MGEs) in addition to species identification may lead to better personalized therapy, particularly in chronic infections.
Insights
Prophage domestication in Staphylococcus aureus significantly increases virulence factors and immune evasion. This finding suggests targeting mobile genetic elements could improve personalized therapies for chronic infections.
Area of Science:
- Microbiology
- Bacterial Genetics
- Infectious Diseases
Background:
- Staphylococcus aureus strains with varying virulence are common in chronic rhinosinusitis (CRS).
- Prophage-encoded virulence, especially from φSa3int (NM3) prophages, is known, but its impact on bacterial gene expression and resident prophages is less understood.
Purpose of the Study:
- To investigate how new prophage domestication affects bacterial gene expression and resident prophage expression.
- To understand the role of φSa3int prophage domestication in Staphylococcus aureus virulence and immune evasion.
Main Methods:
- Transduction of a φSa3int prophage from a hyper-biofilm forming mucoid S. aureus (SA333) into a high-biofilm forming non-mucoid S. aureus (SA222).
- Analysis of gene expression changes, exoprotein production, and phagocytosis rates post-prophage domestication.
Main Results:
- φSa3int prophage domestication led to significant upregulation of 21 exoproteins, including immune-evasion toxins and IcaB.
- Domestication resulted in reduced phagocytosis, indicating enhanced bacterial escape from innate immunity.
- Prophage domestication altered the expression of bacterial genes and suppressed resident prophage structural proteins.
Conclusions:
- φSa3int prophage domestication enhances Staphylococcus aureus virulence through novel factors and immune evasion.
- Targeting virulence factors on mobile genetic elements is crucial for personalized therapies in chronic infections.
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