<i>Staphylococcus aureus</i>
            Fibronectin-Binding Proteins Contribute to Colonization of the Female Reproductive Tract

Lyon, Laurie M; Doran, Kelly S.; Horswill, Alexander R.

doi:10.1128/iai.00460-22

Cited by 7 publications

(2 citation statements)

References 101 publications

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“…A denser, layered Fn fibril network at the surface of osteoblasts demonstrated a poorer uptake of bacteria compared to a moderate Fn fibril network at the surface of A549 epithelial cells suggesting that an optimal concentration and organization of Fn is required for efficient adhesion and uptake. Furthermore, and also in agreement with our results, a recent study has demonstrated that anti-α5β1 antibodies demonstrate no effect on staphylococcal adhesion but abrogate internalization ( 53 ). We, therefore, suggest that clustering of SDC-1 by CD9 and the resulting Fn fibril formation drives the initial adherence of S. aureus .…”

Section: Discussionsupporting

confidence: 93%

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

Green

Issa

Albaldi

et al. 2023

mBio

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Epithelial colonization is a critical first step in bacterial pathogenesis. Staphylococcus aureus can utilize several host factors to associate with cells, including α5β1 integrin and heparan sulfate proteoglycans, such as the syndecans. Here, we demonstrate that a partner protein of both integrins and syndecans, the host membrane adapter protein tetraspanin CD9, is essential for syndecan-mediated staphylococcal adhesion. Fibronectin is also essential in this process, while integrins are only critical for post-adhesion entry into human epithelial cells. Treatment of epithelial cells with CD9-derived peptide or heparin caused significant reductions in staphylococcal adherence, dependent on both CD9 and syndecan-1. Exogenous fibronectin caused a CD9-dependent increase in staphylococcal adhesion, whereas blockade of β1 integrins did not affect adhesion but did reduce the subsequent internalization of adhered bacteria. CD9 disruption or deletion increased β1 integrin-mediated internalization, suggesting that CD9 coordinates sequential staphylococcal adhesion and internalization. CD9 controls staphylococcal adhesion through syndecan-1, using a mechanism that likely requires CD9-mediated syndecan organization to correctly display fibronectin at the host cell surface. We propose that CD9-derived peptides or heparin analogs could be developed as anti-adhesion treatments to inhibit the initial stages of staphylococcal pathogenesis. IMPORTANCE Staphylococcus aureus infection is a significant cause of disease and morbidity. Staphylococci utilize multiple adhesion pathways to associate with epithelial cells, including interactions with proteoglycans or β1 integrins through a fibronectin bridge. Interference with another host protein, tetraspanin CD9, halves staphylococcal adherence to epithelial cells, although CD9 does not interact directly with bacteria. Here, we define the role of CD9 in staphylococcal adherence and uptake, observing that CD9 coordinates syndecan-1, fibronectin, and β1 integrins to allow efficient staphylococcal infection. Two treatments that disrupt this action are effective and may provide an alternative to antibiotics. We provide insights into the mechanisms that underlie staphylococcal infection of host cells, linking two known adhesion pathways together through CD9 for the first time.

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Section: Discussionsupporting

confidence: 93%

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

Green

Issa

Albaldi

et al. 2023

mBio

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“…Staphylococcus aureus (S. aureus) is a major bacterium responsible for nosocomial and community-acquired infections in humans, and these infections have persisted despite widespread prevention interventions (Becker and Bubeck Wardenburg 2015;Kadariya et al 2014;Linzner et al 2021). In addition to an increase in S. aureus infections in pregnant and postpartum women, as well as outbreaks in newborn nurseries, there have been reports of S. aureus colonization of the female vaginal tract (Deng et al 2019;Lyon et al 2023). S. aureus can produce toxins under various environmental conditions and can cause a variety of diseases, ranging from minor infections of the epidermis and soft tissues to life-threatening illnesses (Chen et al 2022;Gherardi 2023).…”

Section: Introductionmentioning

confidence: 99%

Functional rolling circle amplification-based sensitive determination and low-speed centrifugation-based isolation of Staphylococcus aureus

Gao,

Li,

Wang

et al. 2023

J Anal Sci Technol

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The ability to quickly and accurately analyze Staphylococcus aureus (S. aureus) and isolate the bacteria in a simplified setting is crucial for the early identification and treatment of infectious illnesses. Here, we describe the development of a new aptamer-based detection and separation technique that combines Mg2+-dependent DNAzyme amplification cascades with catalytic hairpin assembly for enhanced sensitivity. This technique uses a rolling circle amplification procedure to build a detection scaffold with a repetitive functional hairpin structure that, upon identifying S. aureus, can launch a catalytic hairpin assembly-mediated DNAzyme-based cascade signal amplification. This allows S. aureus to be isolated using low-speed centrifugation and simultaneously quantified. The approach has a low limit of detection of 21 cfu/mL and a broad detection range of six orders of magnitude due to the inclusion of the catalytic hairpin assembly for signal amplification. In addition to high sensitivity, the method also demonstrates high selectivity for the identification and isolation of S. aureus, making it a useful instrument for reporting S. aureus infections.

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Cervicovaginal microbiota disorder combined with the change of cytosine phosphate guanine motif- toll like receptor 9 axis was associated with cervical cancerization

Zheng,

Hu,

Liu

et al. 2023

J Cancer Res Clin Oncol

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Staphylococcus aureus Fibronectin-Binding Proteins Contribute to Colonization of the Female Reproductive Tract

Cited by 7 publications

References 101 publications

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

Functional rolling circle amplification-based sensitive determination and low-speed centrifugation-based isolation of Staphylococcus aureus

Cervicovaginal microbiota disorder combined with the change of cytosine phosphate guanine motif- toll like receptor 9 axis was associated with cervical cancerization

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