Streptococcus gallolyticus, infective endocarditis, and colon carcinoma: new light on an intriguing coincidence.

The coincidence of infective endocarditis (IE) caused by the organism Streptococcus gallolyticus (subsp gallolyticus, also referred to as Streptococcus bovis biotype I) and colon carcinoma has piqued the interest of infectious disease clinicians since an association between enterococcal endocarditis and sigmoid carcinoma was first documented in 1951 [1]. For more than 5 decades, the association between S. bovis IE and carcinoma of the colon has been the subject of numerous case reports [2–4]. In fact, statistics from the 1980s suggest that upwards of twothirds of patients with S. bovis endocarditis were subsequently found to have malignant gastrointestinal tumors [5]. This well-documented association of IE of suspected S. bovis origin with colon carcinoma has changed contemporary clinical practice such that a diagnosis of S. gallolyticus subsp gallolyticus (SG) endocarditis or bacteremia often results in immediate referral of the patient for colonoscopy, in many cases prior to discharge from the hospital. Despite more than 2 dozen case reports, there has been no explanation for the coincidence of SG IE and colon carcinoma, and, in fact, this area of research has been relatively neglected until the past decade. In this issue of the Journal, Boleij and colleagues [6] provide important data pointing to several virulence characteristics of SG that may play key roles in the pathogenesis of this remarkably adaptable organism. These investigators replicated the route of SG infection in vitro by using differentiated human epithelial colorectal adenocarcinoma cells (Caco-2) in a series of assays focusing on both bacterial and host cell responses. These studies focused on SG adhesion, invasion, translocation, biofilm formation, and ability to elicit an immune response in order to identify virulence characteristics that could provide an explanation for the link between SG IE and colon carcinoma. The results of this work suggest that this species of bacteria is uniquely able to translocate in a paracellular fashion across malignant intestinal epithelium without eliciting a significant immune response and then adhere to collagenrich surfaces and form biofilms. These data are exciting in that they address the key putative first steps in the dissemination of the bacteria from the gut environment to the bloodstream and ultimately to other locations more favorable for colonization, such as collagen-rich surfaces of cardiac valves. Future studies can now build on this work by focusing on specific virulence factors responsible for these specific characteristics observed for SG, but not for other related streptococci and other far more numerous bacterial species inhabiting the gut. What is unique about SG that it can exhibit these distinct properties? SG is a mannitol fermentation-positive member of the S. bovis group of group D streptococci and is found in the gastrointestinal tract of birds, ruminants, and a small proportion (2.5%–15%) of humans [3, 7]. Consumption of a highsugar diet by ruminants can cause SG overgrowth, resulting in an overproduction of lactic acid in the gut, a condition called feedlot bloat [8]. SG grows in pairs or chains, is nonmotile, and is non-c-hemolytic or minimally c-hemolytic. Historically, this strain has been referred to as S. bovis biotype I, but within the past decade, the S. bovis group of organisms was divided into 4 major Streptococcus species (S. gallolyticus, S. infantarius, S. macedonicus, and S. pasteurianus), of which S. gallolyticus is the species most often linked to cases of IE [9], although infection by other streptococcal strains has also been linked to colon carcinoma [2]. Recent data Received and accepted 22 December 2010. Potential conflicts of interest: none reported. Reprints or correspondence: Mary E. Hensler, PhD, Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0687 ([email protected]). The Journal of Infectious Diseases 2011;203:1040–2 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected] 1537-6613/2011/2038-0001$15.00 DOI: 10.1093/infdis/jiq170