Epidemiology 

The epidemiology of S. mitis needs to be better studied compared to its close relative, Streptococcus pneumoniae (pneumococcus), a prominent human pathogen and a common cause of respiratory and invasive infections. However, some aspects of the epidemiology of S. mitis can be inferred from the available literature and data. Some of these are: 

• Transmission: S. mitis can be transmitted through intimate contact with saliva, respiratory droplets, or other body fluids from one person to another or blood. It can also be acquired from the environment or medical devices contaminated with the bacterium. S. mitis is prevalent in the normal flora of the oropharynx, where it can colonize up to 90% of healthy individuals. It can also be found in other sites, such as the skin, gastrointestinal tract, and genital tract. 
• Risk factors: S. mitis can cause infections and diseases in individuals with predisposing factors that compromise their immune system or damage their mucosal barriers. These factors include diabetes, cancer, HIV infection, organ transplantation, chemotherapy, radiotherapy, surgery, trauma, dental procedures, and indwelling catheters or prosthetic devices. S. mitis can also cause infections in pregnant women and neonates, as it can cross the placental barrier and cause chorioamnionitis and septicemia. 
• Serotyping: S. mitis can be serotyped based on its capsular polysaccharide antigens. However, unlike S. pneumoniae, with more than 90 serotypes identified, S. mitis has only 12 serotypes reported. Serotyping can help to determine the epidemiological distribution and diversity of S. mitis strains and their association with different clinical outcomes. 
• According to a study conducted in 2014, S. mitis was the most frequently identified species among 118 unique VGS strains causing bacteremia in patients with cancer. The study reported that patients infected with S. mitis strains were likelier to have moderate or severe clinical disease (e.g., VGS shock syndrome) associated with a high mortality rate. 
• According to the CDC, streptococcal toxic shock syndrome (STSS) is a rare but life-threatening complication of streptococcal infections, including those caused by S. mitis. STSS is characterized by hypotension, multiorgan failure, and high fever. Despite rigorous treatment, between 30% and 70% of STSS patients die. Compared to adults, children have a significantly lower rate of STSS mortality.  
• According to a recent article published in 2023, the global prevalence of methicillin-resistant S. mitis (MRSM) is estimated to be around 10%, with higher rates in some regions such as Asia and Europe. MRSM is a significant concern for public health as it limits the treatment options and increases the risk of treatment failure and mortality. A national cohort study conducted in the United States indicated that MRSA colonization. 

Classification and Structure 

Gram-positive streptococcus mitis is a member of the viridans group of streptococci. It is a member of the oral microbiota commonly found in the human oral cavity as a commensal organism. However, it can also be an opportunistic pathogen, causing infections when it enters other parts of the body and causes infections such as endocarditis, bacteremia, and meningitis. 

• Kingdom: Bacteria 
• Phylum: Firmicutes 
• Bacilli: Category 
• Order: Lactobacillales 
• Family: Streptococcaceae 
• Genus: Streptococcus 
• Species: Streptococcus mitis 

Like other streptococci, Streptococcus mitis is a spherical bacterium that usually occurs in pairs or chains. It lacks the outer membrane found in Gram-negative bacteria and has a thick peptidoglycan layer in its cell wall, which gives it its Gram-positive classification. The cell wall of S. mitis contains carbohydrates, lipoteichoic acids, and peptidoglycans. 

The bacterium may have various surface proteins and adhesins that help it interact with host tissues in the oral cavity. These features can contribute to its commensal or pathogenic behavior, depending on the circumstances. 

Antigenic Types 

There are different antigenic types of Streptococcus mitis based on various criteria. Some of these are: 

• Lancefield serologic groups: These are based on the antigenic differences in the cell wall carbohydrates of Streptococci. Streptococcus mitis belongs to the Lancefield group O, one of the 20 groups designated by the letters A to V. However, not all pathogenic Streptococci can be identified by Lancefield typing, such as Streptococcus pneumoniae. 
• Mitis group: This is based on Streptococci’s 16S rRNA gene sequences and nucleic acid hybridization data. Streptococcus mitis is the mitis group’s primary species, consisting of 12 other species, including the highly pathogenic Streptococcus pneumoniae. The mitis group is one of the six groups within the viridans group of Streptococci, which are alpha-hemolytic and colonize the oral cavity. 
• Competence types: These are based on the ability of Streptococci to take up exogenous DNA and incorporate it into their genome by homologous recombination. Streptococcus mitis is competent for natural genetic transformation and can employ a predatory fratricidal mechanism to acquire homologous DNA actively. Streptococcus mitis has four competence types (I to IV), which differ in their competence regulation systems and pheromone peptides. 

Pathogenesis 

Streptococcus mitis is a bacterium that usually lives in the human body as a harmless commensal, but it can also cause infections and diseases, especially in immunocompromised individuals. Some infections caused by S. mitis are endocarditis, scarlet fever, impetigo, glomerulonephritis, rheumatic fever, cellulitis, and necrotizing fasciitis. 

The pathogenesis of S. mitis involves the following steps: 

• Transmission: S. mitis can be transmitted through intimate contact with saliva, respiratory droplets, or other body fluids from one person to another or blood. It can also be acquired from the environment or medical devices contaminated with the bacterium. 
• Adhesion/ Attachment/ Colonization: S. mitis can adhere to various surfaces and tissues in the human body, such as the oral cavity, nasopharynx, throat, skin, gastrointestinal tract, and genital tract. It can also attach to damaged or artificial heart valves and cause endocarditis. S. mitis uses surface and phage proteins to mediate its adhesion and colonization. 
• Invasion: S. mitis can invade the host cells and tissues by producing hyaluronidase, neuraminidase, and IgA1 protease that degrade the extracellular matrix and mucosal barriers. It can also evade the host immune system by expressing antigenic variation, capsule, and cytolysin. 
• Interaction with the immune system: S. mitis can trigger an inflammatory response in the host by activating the complement system, cytokines, and chemokines. It can also induce apoptosis and necrosis of the host cells by releasing toxins and cytolysin. 

Host Defenses 

The innate and adaptive immune system mediates host defenses against S. mitis. Mucous membranes and the skin serve as physical barriers, as well as cellular and molecular elements like phagocytes, complement, cytokines, & antimicrobial peptides, make up the innate immune system. The adaptive immune system comprises the lymphocytes, B and T cells, and antibodies that can recognize specific antigens on the surface of S. mitis. 

Some of the host defense mechanisms against S. mitis are: 

• Phagocytosis: This is the process by which phagocytes, such as neutrophils and macrophages, engulf and destroy foreign particles or microorganisms. Opsonization enhances phagocytosis, which is the coating of S. mitis with antibodies or complement proteins that facilitate their recognition and binding by phagocytes. 
• Complement activation: This is the activation of a cascade of plasma proteins that leads to the formation of membrane attack complexes (MACs) that insert into the cell wall of S. mitis and cause lysis. Complement activation also promotes inflammation, chemotaxis, opsonization, and clearance of immune complexes. 
• Antimicrobial peptides: These are small peptides produced by various cells and tissues with direct bactericidal activity against S. mitis. Some examples of antimicrobial peptides are defensins, cathelicidins, histatins, and lactoferrin. 
• Antibody production: This is the production of specific antibodies by B cells that bind to antigens on the surface of S. mitis and neutralize them or mark them for destruction by other immune cells or complement. Additionally, antibodies can activate the traditional complement activation pathway. 
• Cell-mediated immunity: This is the activation of T cells that recognize antigens presented by antigen-presenting cells (APCs), such as dendritic cells or macrophages. T cells can secrete cytokines that regulate the immune response or kill infected cells or S. mitis by releasing perforin and granzymes. 

Clinical manifestations 

The clinical manifestations of Streptococcus mitis are: 

• Endocarditis is a sickness of the heart inside lining chambers and valves. One of the main causes of infective endocarditis and bacteremia associated with viridans streptococci is streptococcus mitis. Symptoms of endocarditis include tiredness, weakness, fever, weight loss, respiratory problems, and problems with heart function. 
• Scarlet fever: This bacterial infection causes a distinctive red rash on the skin. Streptococcus mitis can cause scarlet fever along with other species of Streptococci. Symptoms of scarlet fever include sore throat, fever, headache, swollen glands, and a strawberry-like tongue. 
• Impetigo: This skin infection causes red sores that can burst and form crusts. Streptococcus mitis can cause impetigo along with other species of Streptococci. Impetigo is more common in children and can spread quickly through contact with infected skin or objects. 
• Glomerulonephritis: This kidney disease causes inflammation and damage to the glomeruli, which are the tiny filters in the kidneys that drain the blood of extra fluid and waste. Along with other species of Streptococci, Streptococcus mitis may result in glomerulonephritis. Glomerulonephritis is a potentially severe side effect of streptococcal infections, including pharyngitis and impetigo. Blood in the urine, protein in the urine, bloating of the face or limbs, increased blood pressure, & decreased urine output are all signs of glomerulonephritis. 

• Rheumatic fever: This inflammatory condition may affect the heart, joints, skin, and brain. Streptococcus mitis can cause rheumatic fever along with other species of Streptococci. Rheumatic fever can be a complication of untreated or poorly treated streptococcal infections such as pharyngitis or scarlet fever. Rheumatic fever symptoms include fever and joint pain. And swelling, chest pain, shortness of breath, skin rash, and involuntary movements. 
• Cellulitis: This bacterial infection results in redness, swelling, and pain. Pain and warmth in the affected area of the skin. Streptococcus mitis can cause cellulitis along with other species of Streptococci. Cellulitis can occur when bacteria enter through a break in the skin, such as a cut, wound, insect bite, or ulcer. Cellulitis can affect any body part but is more common in the lower legs. 

Diagnosis 

Techniques for recognizing and separating S. mitis from other streptococci 

• Morphological, Cultural, and Biochemical Characteristics: Gram-positive coccus forming chains/pairs, catalase-negative, oxidase-positive, alpha-hemolytic on blood agar, ferments glucose, lactose, sucrose, and maltose but not mannitol or sorbitol. Produces hyaluronidase, neuraminidase, and IgA1 protease. 
• Rapid Diagnosis: Commercial kits like Rapid ID 32 Strep system (32 biochemical tests) and AccuProbe Streptococcus pneumoniae Culture Identification Test (detects pneumolysin gene) can quickly identify S. mitis. 

• Molecular Diagnosis: PCR amplifies specific S. mitis DNA regions with primers or probes. 16S rRNA gene sequencing compares sequences for precise identification. 

Control 

Ways to prevent Streptococcus mitis and other streptococcal infections: 

• Practice good hygiene: Wash hands, cover mouth when coughing/sneezing, and avoid sharing personal items. 
• Seek medical attention for symptoms: Sore throat, fever, rash, or skin sores. 
• Follow the advice for medical conditions: Take preventive antibiotics if at higher risk (diabetes, cancer, heart disease, dental problems). 
• Get vaccinated: For certain streptococcal infections (e.g., pneumococcal disease, rheumatic fever)—no vaccine for Streptococcus mitis yet; ongoing research. 

References 

• Streptococcus Mitis – an overview | ScienceDirect Topics 
• Streptococcus mitis – microbewiki (kenyon.edu)