A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune Evasion
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...
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Wiley
2025-08-01
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| Online Access: | https://doi.org/10.1002/mco2.70313 |
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| author | Roshan Nepal Ghais Houtak George Bouras Sholeh Feizi Gohar Shaghayegh Keith Shearwin Mahnaz Ramezanpour Alkis James Psaltis Peter‐John Wormald Sarah Vreugde |
| author_facet | Roshan Nepal Ghais Houtak George Bouras Sholeh Feizi Gohar Shaghayegh Keith Shearwin Mahnaz Ramezanpour Alkis James Psaltis Peter‐John Wormald Sarah Vreugde |
| author_sort | Roshan Nepal |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-749207fb688c41f7984fe14a6aaebc51 |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-749207fb688c41f7984fe14a6aaebc512025-08-20T04:02:50ZengWileyMedComm2688-26632025-08-0168n/an/a10.1002/mco2.70313A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune EvasionRoshan Nepal0Ghais Houtak1George Bouras2Sholeh Feizi3Gohar Shaghayegh4Keith Shearwin5Mahnaz Ramezanpour6Alkis James Psaltis7Peter‐John Wormald8Sarah Vreugde9The Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaSchool of Biological Sciences Faculty of Sciences Engineering and Technology The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaThe Faculty of Health and Medical Sciences The University of Adelaide Adelaide AustraliaABSTRACT 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.https://doi.org/10.1002/mco2.70313bacteriophagechronic rhinosinusitismicrobe–host interactionNM3 prophagephageSa3int prophage |
| spellingShingle | Roshan Nepal Ghais Houtak George Bouras Sholeh Feizi Gohar Shaghayegh Keith Shearwin Mahnaz Ramezanpour Alkis James Psaltis Peter‐John Wormald Sarah Vreugde A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune Evasion MedComm bacteriophage chronic rhinosinusitis microbe–host interaction NM3 prophage phage Sa3int prophage |
| title | A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune Evasion |
| title_full | A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune Evasion |
| title_fullStr | A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune Evasion |
| title_full_unstemmed | A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune Evasion |
| title_short | A φSa3int (NM3) Prophage Domestication in Staphylococcus aureus Leads to Increased Virulence Through Human Immune Evasion |
| title_sort | φsa3int nm3 prophage domestication in staphylococcus aureus leads to increased virulence through human immune evasion |
| topic | bacteriophage chronic rhinosinusitis microbe–host interaction NM3 prophage phage Sa3int prophage |
| url | https://doi.org/10.1002/mco2.70313 |
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