Contribution of Streptococcus anginosus to Infections Caused by Groups C and G Streptococci, Southern India

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Volume 16, Number 4–April 2010
Research
Contribution of Streptococcus anginosus to Infections Caused by Groups C and G Streptococci, Southern India
Silvana Reißmann, Claudia Friedrichs, Reena Rajkumari, Andreas Itzek, Marcus Fulde, Arne C. Rodloff, Kootallur N. Brahmadathan, Gursharan S. Chhatwal, and D. Patric Nitsche-Schmitz
Author affiliations: Helmholtz Centre for Infection Research, Braunschweig, Germany (S. Reißmann, A. Itzek, M. Fulde, G.S. Chhatwal, D.P. Nitsche-Schmitz); University Hospital Leipzig, Leipzig, Germany (C. Friedrichs, A.C. Rodloff); and Christian Medical College, Vellore, Tamil Nadu, India (R. Rajkumari, K.N. Brahmadathan)

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Abstract
Vellore, a region in southern India, has a high incidence of severe human infections with β-hemolytic group C and G streptococci (GCGS). To determine the causative species in these infections, we conducted 16S rRNA gene sequencing: Streptococcus dysgalactiae subsp. equisimilis (81%) and S. anginosus (19%) were the causative organisms in the 2-year study period (2006–2007). We used PCR to detect the virulence-related emm gene; results showed that it was restricted to S. dysgalactieae subsp. equisimilis isolates of 99.2% tested positive. Due to a novel marker, S. anginosus and S. constellatus can be quickly and accurately distinguished from other members of the genus. The notable contribution of the anginosus group to human infections suggests that this group of obligate pathogens deserves more attention in healthcare and research.

Group C and group G streptococci (together GCGS) were first recognized as human pathogens in 1935 by Lancefield and Hare (1). Since then, awareness about their importance has greatly increased, especially within recent years (2–6). Similar to infections with Streptococcus pyogenes, the prime example of a pyogenic streptococcal pathogen, infections with GCGS can develop into life-threatening necrotizing fasciitis, sepsis, and streptococcal toxic shock–like syndrome. Lancefield groups C and G comprise a variety of species; one of those species, Streptococcus dysgalactiae subsp. equisimilis (SDSE), frequently causes human infections. This species can cause the whole spectrum of infections caused by S. pyogenes (4,5).

SDSE likely owes its virulence in humans to homologs of prominent S. pyogenes virulence genes (7,8). Most SDSE strains isolated from human infections possess emm genes (9,10), which code for the potent virulence factor called M protein (11). This surface localized protein contributes substantially toward the virulence of both S. pyogenes and SDSE in human hosts because it acts as an adhesin, invasin, and antiphagocytic factor (11). Strain-to-strain variability in the N terminus of M proteins, driven by the adaptive immune response of the host, has led to a vast emm type diversity. More than 100 genetically distinct M proteins exist within the GCGS group and form the basis for emm genotyping (12). However, SDSE is not the only species that causes severe diseases in humans. The variety of GCGS includes the typical animal pathogens S. equi subsp. zooepidemicus (group C) and S. canis (group G), which have the potential to cause zoonotic infections (13,14). Other streptococcal species that are pathogenic in humans and that occasionally expose groups C and G carbohydrates are gathered under the umbrella term anginosus group (15).

In the literature, the designation S. milleri (16) has often been used for streptococci of this group, although it has never been an officially approved name (15). Streptococci of the anginosus group can reside commensally in the human oral cavity but have a certain propensity to cause pharyngitis, bacteremia, and serious purulent infections in the deep neck and soft tissue and in internal organs such as the brain, lung, and liver (17–25). The bacteria cause severe infections after surgical treatments and infect implanted material, thereby posing a problem of substantial clinical relevance (20,26,27). The species diversity within the GCGS highlights the limits of Lancefield grouping by agglutination assays, the typically applied method in the diagnosis of streptococcal infections. The genetically distinct GCGS species differ in pathogenesis, virulence mechanisms, and antimicrobial drug susceptibility. Thus, finding the optimal treatment regimen can be facilitated by species determination. Diagnosis of anginosus group infections is particularly difficult. The group comprises the species S. anginosus, S. intermedius, and S. constellatus of which the 2 subspecies, S. constellatus subsp. constellatus and S. constellatus subsp. pharyngis, are further distinguished. Identification of the anginosus group is complicated by wide phenotypic and antigenic diversity, even within 1 species. Although most anginosus group isolates belong to the non-β-hemolytic oral streptococci, β-hemolytic strains are found in all 3 species. Some anginosus group strains carry a typeable Lancefield group antigen, which belongs to group F, C, G, or A (28).

Routine microbiologic diagnosis of streptococcal infections is often restricted to determination of the type of hemolysis and of the Lancefield group. Identification of streptococci to the species level is rarely carried out. This leaves a considerable risk for misidentification of causative pathogens, which can lead to an inappropriate treatment of the infection (29–31). As a further consequence of the complications associated with species determination, insight into the epidemiology of infections with certain streptococci remains imprecise, and the epidemiology of the anginosus group, in particular, remains widely elusive. Comprehensive insights are missing that could enable clinicians to reevaluate respective diagnostic and therapeutic routines. Moreover, such insights may stimulate research that aims at clarifying the pathogenesis of these streptococcal species and the development of specialized treatments and prevention strategies. These goals have motivated our cross-species study of human pathogenic GCGS from Vellore, India, a region with a high incidence of such infections. Examination of epidemiologic contributions of the different streptococcal species was combined with a cross-species screening for emm genes, which identified a novel gene in S. anginosus and S. constellatus. The use of this gene as a marker for fast detection of infections caused by these 2 streptococcal species was investigated.

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Suggested Citation for this Article
Reißmann S, Friedrichs C, Rajkumari R, Itzek A, Fulde M, Rodloff AC, et al. Contribution of Streptococcus anginosus to infections caused by groups C and G streptococci, southern India. Emerg Infect Dis [serial on the Internet]. 2010 Apr [date cited]. Available from http://www.cdc.gov/EID/content/16/4/656.htm

DOI: 10.3201/eid1604.090448