A Globally Disseminated M1 Subclone of Group A Streptococci Differs from Other Subclones by 70 Kilobases of Prophage DNA and Capacity for High-Frequency Intracellular Invasion

Abstract

The M1inv+ subclone of M1 group A streptococci that spread globally in the late 1980s and early 1990s was previously identified by restriction fragment length polymorphism (RFLP), M protein, and SpeA exotoxin sequence analyses. Strains representing this subclone were characterized with regard to carriage of bacteriophage and capacity to invade cultured human epithelial cells. The M1inv+ subclone was found to harbor two entirely different prophages, phage T13 and phage T14, which together supplement its genome with nearly 70 kb of DNA. Phage T14 encodes the SpeA exotoxin and is closely related to the classic converting phage T12. Plaque-forming characteristics and RFLP analyses of phages T13 and T14 were compared to each other and to phage T12. Other subclones of M1, isolated in the 1970s to the early 1980s, lacked both prophages. The M1inv+ subclone was previously reported to be efficiently internalized by human epithelial cells. This potential was confirmed and expanded by comparing a variety of clinical isolates. The capacity for high-frequency invasion of epithelial cells was not transmitted to a laboratory strain of group A streptococci by the above-mentioned bacteriophages.

Mutational analysis of the group A streptococcal operon encoding streptolysin S and its virulence role in invasive infection

“…Prominent among invasive GAS syndromes are the destructive soft tissue infection necrotizing fasciitis (NF) and the multisystem disorder of streptococcal toxic shock syndrome (STSS), each carrying significant risk of morbidity and mortality even with aggressive medical therapy (Stevens, 1999;Sharkawy et al ., 2002). While GAS strains of many M protein ( emm ) genotypes are capable of producing significant disease, strains representing one globally disseminated clonal M1T1 GAS strain have persisted for over 20 years as the single most prevalent isolate from invasive GAS infections (Cockerill et al ., 1997;Cleary et al ., 1998;Murono et al ., 1999;Chatellier et al ., 2000), including all nine surveillance centres of the United States Centers for Disease Control Emerging Infections Program Network in 2002 (http://www.cdc.gov/ncidod/ dbmd/abcs).…”

Post‐proteomic identification of a novel phage‐encoded streptodornase, Sda1, in invasive M1T1 Streptococcus pyogenes

“…M1T1 lacks the speC gene but carries the speA gene (Musser et al ., 1995;Chatellier et al ., 2000). Many of these differences are attributed to mobile genetic elements, such as transposons, insertion sequences and lysogenic bacteriophages that have been inserted in the GAS genome throughout the years (Cleary et al ., 1998;Banks et al ., 2002). GAS bacteriophages encode at least three classes of extracellular virulence proteins: superantigens, phospholipases and streptodornases (Banks et al ., 2002;Boyd and Brussow, 2002;Canchaya et al ., 2003).…”

The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells

“…The aetiology of the invading bacteria and the outcome of GAS internalization into eukaryotic cells is still under debate. There is epidemiological and experimental data associating this property with the bacterial ability to invade tissues and cause systemic GAS infections (‘high‐virulence phenotype’) (LaPenta et al ., 1994; Cleary et al ., 1998a) as well as with a low‐virulence phenotype required for asymptomatic persistence of GAS in their human host (Österlund and Engstrand, 1998; Molinari and Chhatwal, 1998, 1999a; Sela and Barzilai, 1999).…”