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Updated: Aug 17, 2025
Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Staphylococcus aureus Fibronectin-Binding Proteins Contribute to Colonization of the Female Reproductive Tract
Laurie M Lyon1, Kelly S Doran1, Alexander R Horswill1,2
1Department of Immunology and Microbiology, University of Colorado, Aurora, Colorado, USA.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen and frequent colonizer of human skin and mucosal membranes, including the vagina, with vaginal colonization reaching nearly 25% in some pregnant populations. MRSA vaginal colonization can lead to aerobic vaginitis (AV), and during pregnancy, bacterial ascension into the upper reproductive tract can lead to adverse birth outcomes. USA300, the most prominent MRSA lineage to colonize pregnant individuals, is a robust biofilm former and causative agent of invasive infections; however, little is known about how it colonizes and ascends in the female reproductive tract (FRT). Our previous studies showed that a MRSA mutant of seven fibrinogen-binding adhesins was deficient in FRT epithelial attachment and colonization. Using both monolayer and multilayer air-liquid interface cell culture models, we determine that one class of these adhesins, the fibronectin binding proteins (FnBPA and FnBPB), are critical for association with human vaginal epithelial cells (hVECs) and hVEC invasion through interactions with α5β1 integrin. We observe that both FnBPs are important for biofilm formation as single and double fnbAB mutants exhibit reduced biofilm formation on hVECs. Using heterologous expression of fnbA and fnbB in Staphylococcus carnosus, FnBPs are also found to be sufficient for hVEC cellular association, invasion, and biofilm formation. In addition, we found that an ΔfnbAB mutant displays attenuated ascension in our murine vaginal colonization model. Better understanding of MRSA FRT colonization and ascension can ultimately inform treatment strategies to limit MRSA vaginal burden or prevent ascension, especially during pregnancy and in those prone to AV.
Insights
Methicillin-resistant Staphylococcus aureus (MRSA) fibronectin binding proteins (FnBPs) are key for vaginal colonization and invasion. Understanding these adhesins can help prevent adverse pregnancy outcomes linked to MRSA.
Area of Science:
- Microbiology
- Infectious Diseases
- Obstetrics and Gynecology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) frequently colonizes the vagina, particularly in pregnant individuals, posing risks for aerobic vaginitis (AV) and adverse birth outcomes.
- The USA300 MRSA lineage is a common colonizer and invasive pathogen, yet its mechanisms for colonizing and ascending the female reproductive tract (FRT) remain unclear.
- Previous research indicated that MRSA mutants lacking fibrinogen-binding adhesins show reduced FRT colonization.
Purpose of the Study:
- To investigate the role of specific MRSA adhesins, particularly fibronectin binding proteins (FnBPs), in vaginal epithelial cell association, invasion, and biofilm formation.
- To determine the contribution of FnBPs to MRSA ascension in the female reproductive tract.
- To elucidate the molecular mechanisms underlying MRSA colonization and ascension in the FRT.
Main Methods:
- Utilized monolayer and multilayer air-liquid interface cell culture models with human vaginal epithelial cells (hVECs).
- Investigated MRSA mutants (single and double fnbAB mutants) and heterologous expression systems (Staphylococcus carnosus).
- Employed a murine vaginal colonization model to assess bacterial ascension.
Main Results:
- Fibronectin binding proteins (FnBPA and FnBPB) were identified as critical for MRSA association with and invasion into hVECs, mediated by α5β1 integrin.
- Both FnBPs are essential for robust MRSA biofilm formation on hVECs, as evidenced by reduced biofilm formation in fnbAB mutants.
- An ΔfnbAB mutant exhibited significantly attenuated ascension in the murine vaginal colonization model.
Conclusions:
- FnBPs are crucial virulence factors for MRSA colonization, invasion, and biofilm formation within the female reproductive tract.
- Targeting FnBP-mediated interactions could be a therapeutic strategy to reduce MRSA vaginal burden and prevent ascending infections, especially during pregnancy.
- Further understanding of MRSA-FRT interactions is vital for developing interventions against MRSA-associated complications.
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