Abstract

Staphylococcus aureus is the main cause of human skin and soft tissue infections. However, S. aureus pathogenicity within the skin is not fully characterized. Here, we implemented an S. aureus cutaneous infection model using human skin explants and performed a time-course infection to study the gene expression profile of a large panel of virulence-related factors of S. aureus USA300 LAC strain, by high-throughput RT-PCR. We pinpointed the genes that were differentially regulated by the bacteria in the skin tissues and identified 12 virulence factors that were upregulated at all time points assessed. Finally, using confocal microscopy, we show that the expression of alpha-hemolysin by S. aureus varies dependent on the skin niche and that the bacteria preferentially accumulates inside sweat glands and ducts. Taken together, our study gives insights about the pathogenic lifestyle of S. aureus within human skin tissues, which may contribute for the development of anti-S. aureus therapeutic strategies.

Highlights

  • Staphylococcus aureus is an important human pathogen that persistently colonizes 20% of human population and transiently colonizes another 60% (Kluytmans et al, 1997)

  • To investigate colonization and infection of human skin by S. aureus, we first set up a model resembling the natural S. aureus cutaneous infections, using abdominal human skin explants

  • To better understand staphylococcal pathogenesis in human tissues, it is important to determine which bacterial virulence factors are expressed in the context of the infection

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Summary

Introduction

Staphylococcus aureus is an important human pathogen that persistently colonizes 20% of human population and transiently colonizes another 60% (Kluytmans et al, 1997). These bacteria can cause different diseases that range from skin and soft tissue infections (SSTIs) as impetigo, folliculitis, abscesses and cellulitis (Olaniyi et al, 2016), to more invasive diseases like endocarditis, osteomyelitis, pneumonia and sepsis (Lowy, 1998; Salgado-Pabón and Schlievert, 2014). Complex regulatory networks modulate the expression of metabolic and virulence factors and enable the bacteria to adapt to different host environments (Cheung et al, 2004; Balasubramanian et al, 2017; Haag and Bagnoli, 2017; Jenul and Horswill, 2018).

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