Streptococcus gallolyticus is a gram-positive bacterium that normally inhabits the gastrointestinal tract in many healthy individuals. It is primarily recognized as an opportunistic pathogen, causing disease only when the host’s defenses are compromised or when the bacteria translocate outside of the intestinal environment. Its emergence in the bloodstream or heart is significant due to its association with severe systemic infections and an increased risk of colorectal cancer. Understanding this bacterium’s nature and clinical implications is important for timely diagnosis and management.
Identification and Classification
The organism now known as Streptococcus gallolyticus was historically classified as Streptococcus bovis biotype I. This name change, driven by molecular analysis and phylogenetic studies, revealed distinct genetic differences among the strains formerly grouped as S. bovis. The reclassification aimed to provide a more accurate representation of the organism’s unique genetic makeup and clinical associations.
The current classification places the most clinically relevant strain as Streptococcus gallolyticus subsp. gallolyticus. This subspecies is the primary cause of the severe infections and cancer risk associated with the species. Other related subspecies, like S. gallolyticus subsp. pasteurianus, show weaker associations with these serious conditions. This bacterium belongs to the larger Streptococcus bovis/equinus complex and is a common member of the human gut flora.
Infections Beyond the Gut
When S. gallolyticus breaches the intestinal barrier and enters the bloodstream, it causes severe systemic infections, primarily infective endocarditis. This condition involves the infection of the heart’s inner lining, or endocardium, most often affecting the heart valves. S. gallolyticus is a frequent cause of streptococcal endocarditis, accounting for a significant percentage of cases.
The bacterium possesses specific surface proteins, such as the Pil1 pili, that allow it to adhere to the extracellular matrix proteins of heart tissue, particularly collagen. This binding facilitates the formation of vegetations, which are masses of bacteria, platelets, and fibrin that characterize endocarditis. These vegetations can lead to heart valve damage and serious complications, including stroke or heart failure. Another complication is septicemia, which can lead to widespread inflammation and organ dysfunction.
Understanding the Colorectal Cancer Connection
A significant epidemiological link exists between invasive S. gallolyticus infection and the presence of colorectal neoplasia, including adenomas and carcinomas. Studies show that a substantial proportion of patients (25% to 80%) diagnosed with S. gallolyticus bacteremia or endocarditis have a synchronous colorectal tumor. For S. gallolyticus subsp. gallolyticus, the association with an underlying colonic malignancy can be as high as 71%.
The clinical implication is that detecting S. gallolyticus in the blood is considered a sentinel event that mandates a comprehensive search for underlying colorectal cancer (CRC). The bacterium contributes to tumor development through several proposed mechanisms within the gut environment.
One mechanism involves promoting chronic inflammation in the colon, creating an environment conducive to cellular transformation and tumor progression. The bacteria may also directly promote the growth of pre-cancerous cells. Research suggests that S. gallolyticus can upregulate signaling pathways, such as the \(\beta\)-catenin pathway, which are often dysregulated in CRC. This upregulation leads to increased epithelial cell proliferation, accelerating tumor formation. The bacteria may also alter the gut environment by secreting factors, such as bacteriocins, which eliminate competing commensal bacteria, allowing S. gallolyticus to flourish. Because the organism is associated with early adenomas, its presence may serve as a potential early marker for CRC screening.
Clinical Detection and Management
Initial detection of an invasive infection occurs through blood cultures when a patient presents with symptoms of septicemia or endocarditis. If S. gallolyticus is identified in the blood, an echocardiogram is performed to check for the characteristic vegetations on heart valves indicative of infective endocarditis. The definitive step in managing a positive S. gallolyticus blood culture is a mandatory colonoscopy.
This endoscopic procedure is necessary to thoroughly examine the colon and rectum for any polyps or cancerous lesions that may have served as the portal of entry for the bacteria into the bloodstream. The standard treatment involves antibiotic therapy, typically penicillin or a cephalosporin like ceftriaxone. For severe infections, particularly endocarditis, these antibiotics are often combined with an aminoglycoside such as gentamicin to enhance bacterial eradication.
Treatment duration for native valve endocarditis is typically four weeks of intravenous antibiotics. The precise regimen depends on the minimum inhibitory concentration (MIC) of the antibiotic against the isolated strain. If heart valves are extensively damaged or the infection is difficult to clear, surgical intervention may be required to repair or replace the affected valves. Following the acute infection, continued surveillance for colorectal cancer is recommended, even if the initial colonoscopy is negative, due to the persistent risk of developing a tumor years later.