Group A Streptococcus translocates across an epithelial barrier via degradation of intercellular junctionsby Tomoko Sumitomo

Journal of Oral Biosciences

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Text

Review

Group A Streptococcus translocates across an epithelial barrier via degradation of intercellular junctions

Tomoko Sumitomo n

Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka 565-0871, Japan a r t i c l e i n f o

Article history:

Received 21 January 2015

Received in revised form 9 March 2015

Accepted 25 March 2015

Available online 29 April 2015

Keywords:

Group A Streptococcus

Epithelial barrier

Paracellular translocation a b s t r a c t

Background: Streptococcus pyogenes (group A Streptococcus, GAS) is a versatile human pathogen associated with a variety of mucosal and invasive diseases. In order to cause severe invasive diseases,

GAS must penetrate the host epithelial barrier in the pharynx or damaged skin together with evasion of host defense mechanisms. GAS possesses strategies to overcome the epithelial barrier via paracellular and intracellular routes. Here, we review recent findings to better understand the pathogenesis of GAS infection by a transepithelial process via a paracellular route.

Highlight: Recently, we reported that streptolysin S, a determinant for β-hemolysis, facilitates bacterial penetration by degrading epithelial intercellular junctions in concert with host proteases. Furthermore, we provided evidence that a broad spectrum secreted cysteine protease, streptococcal pyrogenic exotoxin B (SepB), directly cleaves transmembrane proteins associated with the epithelial barrier to permit GAS to invade deeper into tissues.

Conclusion: Our investigations of interactions of bacteria with intercellular junctions have provided further insight into the mechanisms used by GAS to disrupt the epithelial barrier. Elucidation of molecular mechanisms underlying the initial stage of GAS infections in these studies may expedite development of novel preventive or therapeutic agents for severe invasive GAS infections. & 2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.

Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 2. Invasion via intracellular route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 3. Overcoming the epithelial barrier via the paracellular route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 3.1. Hyaluronic acid capsule. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 3.2. Streptolysin S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 3.3. SpeB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

Ethical approval. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

Conflict of interest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 1. Introduction

Streptococcus pyogenes (Group A Streptococcus, GAS) is a grampositive bacterium, and a common pathogen causing substantial morbidity and mortality in humans worldwide. GAS is known to be responsible for numerous diseases, ranging from pharyngitis, tonsillitis, and impetigo, to life-threatening invasive diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome [1,2]. Serious postinfection immune sequelae, such as rheumatic fever and acute glomerulonephritis, are also significant problems in developing countries. Although antibiotic therapy is commonly effective against non-invasive diseases, early and

Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/job

Journal of Oral Biosciences http://dx.doi.org/10.1016/j.job.2015.03.002 1349-0079/& 2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved. n Tel.: þ81 6 6879 2897; fax: þ81 6 6879 2180.

E-mail address: sumitomo@dent.osaka-u.ac.jp

Journal of Oral Biosciences 57 (2015) 135–138 aggressive surgical intervention are often required to manage severe invasive diseases [3]. The clinical importance and complications of GAS infections have stimulated interest in vaccine development. However, current strategies for GAS vaccine development remain only in the preliminary stages.

The pharynx and skin are considered to be the primary sites of

GAS infection. To successfully establish colonization, the organisms must gain contact with superficial epithelia at those anatomical sites. Pharyngeal epithelia and keratinocytes are highly specialized physical barriers that protect the underlying sterile tissues from external aggression. Barrier integrity is generally maintained by a series of specialized complexes, including tight junctions, adherence junctions, and desmosomes. Several pathogens utilize the intercellular junctional complexes for their advantage [4–6]. Indeed, loss of cell–cell adhesion together with inadvertent bacterial inoculation is associated with the development of superficial GAS skin infections accompanied by bullous lesions [7].