The heterogeneous genus of Streptococci plays an important role in human disease. Streptococci are estimated to cause 700 million human infections each year worldwide, with an estimated total of 500,000 deaths (Carapetis, McDonald, & Wilson, 2005). Louis Pasteur recognized streptococci as one of the first microorganisms to cause contagious disease in 1879. For family physicians, Streptococcus pyogenes has generally been associated with a sore throat (strep throat) and less often associated with complications, like rheumatic fever or glomerulonephritis. Since the late 1980s, a resurgence of severe infections by S. pyogenes have been reported, which involve expanding and invasive soft tissue infections, as well as necrotizing fasciitis, and which are often accompanied by streptococcal toxic shock syndrome (STSS) (Reglinski & Sriskandan, 2014). In 1998, a sudden onset of neuropsychiatric illness, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) following pharyngitis, was described (Swedo, et al., 1998). During the last decade, it became clear that a related species, S. dysgalactiae subsp. equisimilis, can cause many of the same kinds of human infections with similar complications. Over the past 20 years, β-hemolytic species of streptococci were recognized as highly capable intracellular pathogens that are able to efficiently invade human cells in cell culture. (LaPenta, Rubens, Chi, & Cleary, 1994; Greco, De Martino, Donnarumma, Conte, Seganti, & Valenti, 1995; Rohde & Chhatwal, 2013). Evidence indicates that streptococci can survive and persist within human cells and remain impervious to antibiotic treatment and innate immune defenses.
A well-established assumption is that bacterial pathogens must first attain intimate contact with host extracellular matrix proteins (ECM) on host cells in order to establish successful infections. That initial contact with ECM proteins or cells is accomplished by highly specific adhesins (Courtney, Hasty, & Dale, 2002; Jenkinson & Lamont, 1997; Nobbs, Lamont, & Jenkinson, 2009). Adhesins and other macromolecules that trigger the uptake of bacteria or invasion of the host cells are named invasins. One hallmark of streptococci is the expression of a highly variable and extensive repertoire of adhesins and invasins. Those proteins are differentially regulated and expressed in response to signals from the different environments within the human host (Nobbs, Lamont, & Jenkinson, 2009). Streptococci sometimes use mechanisms similar to those of other intracellular bacterial species and viruses to invade host cells. Due to their variable repertoire of adhesins and invasins, streptococci have evolved numerous strategies to be internalised and survive in host cells for their own benefit, namely escaping antibiotic treatment and the host immune system (Cunningham, 2000; Courtney, Hasty, & Dale, 2002; Nitsche-Schmitz, Rohde, & Chhatwal, 2007; Nobbs, Lamont, & Jenkinson, 2009; Rohde & Chhatwal, 2013; Talay, 2005; Brouwer, Barnett, Rivera-Hernandez, Rohde, & Walker, 2016 for review). This chapter will focus on the extensive repertoire of adhesins and invasins that are expressed by β-hemolytic streptococci and will examine their molecular interactions with host human host cells, as well as address the clinical and epidemiologic relevance of intracellular streptococci.
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