Intracellular Reservoir of Streptococcus pyogenes In Vivo: A Possible Explanation for Recurrent Pharyngotonsillitis

Abstract

Numerous theories have been presented that attempt to explain the frequent recurrences of pharyngotonsillitis caused by Streptococcus pyogenes; these recurrences occur after seemingly adequate antibiotic treatment. We previously have demonstrated that Spyogenes can survive for up to 7 days intracellularly in immortalized human respiratory epithelial cells grown in an antibiotic supplemented medium. Viable S pyogenes were externalized and established an extracellular infection, whenever the extracellular antibiotic was removed. We have investigated the presence of intracellular S pyogenes in two in vivo studies using respiratory epithelial cells collected from patients with tonsillitis and the tonsils of asymptomatic carriers. Electron microscopy and immunohistochemistry demonstrated intracellular S pyogenes in pharyngeal epithelial cells in 13 of 14 patients with tonsillitis (93%). Furthermore, intracellular S pyogenes were found in macrophage-like cells in eight (73%) and in epithelial cells in four (36%) tonsils from 11 asymptomatic S pyogenes carriers. These in vivo data strongly support the hypothesis that intracellular S pyogenes can constitute a reservoir of bacteria with the potential to cause reinfections.

A nonpetide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin α5β1-fibronectin-M1 protein complexes

“…Plus and minus signs indicate the presence or absence of a given reactant in an incubation step. disease (6)(7)(8)(9)(10) S. pyogenes appears incapable of true intracellular growth, and the number of viable, intracellular bacteria declines steadily over time (9,30). Bacterial growth can resume, however, even after several days' exposure to antibiotics, after removal of antibiotics from infected monolayers (8).…”

“…Mammalian cells are poorly permeable to ␤-lactam antibiotics, and there is considerable evidence that the presence of intracellular streptococci in vivo contributes to the frequent failure of ␤-lactams to eradicate the organism from infected persons (8)(9)(10). Collectively, these results suggest that the ability of S. pyogenes to enter host cells may, in effect, confer ␤-lactam resistance on the bacterium.…”

Streptococcal modulation of cellular invasion via TGF-β1 signaling

“…Children frequently retain streptococci in their tonsils after an exhaustive course of antibiotic therapy, accounting for the fact that as many as 30% of healthy school age children have positive throat cultures during the fall-winter months in temperate climates (1,2). Excised tonsil tissue contains viable intra-and extracellular streptococci, suggesting that this organ is a reservoir for recurrent infection and that persistent streptococci are the instigators of chronic changes that lead to hypertrophy (3). A murine intranasal infection model confirmed that GAS has a tropism for nasal associated lymphoid tissue (4).…”

Tonsillar Crypts and Bacterial Invasion of Tonsils: A Pilot Study

“…The recurrent nature of acute tonsillitis has been attributed to the bacteria surviving intracellularly, thus avoiding antibiotic exposure and subsequently escaping the cellular confine to cause reinfection [5].…”