Streptococcus is a diverse genus of bacteria, encompassing species that are ubiquitous members of the human microbiome and others that are significant human and animal pathogens. These bacteria are responsible for a wide spectrum of diseases, ranging from common, mild infections to severe, life-threatening conditions. Understanding the structure of Streptococcus, the mechanisms by which they cause disease, and the development of antibiotic resistance is central to effective medical practice and public health. This article explores the defining biological features of these organisms, the infections they precipitate, and the strategies they employ to evade modern medicine.
Classification and Defining Characteristics
Streptococcus species are Gram-positive bacteria, possessing a thick peptidoglycan cell wall structure that retains the crystal violet stain, a defining feature in laboratory identification. These organisms are non-motile and non-spore-forming. They characteristically grow in pairs or chains, a microscopic arrangement that gives the genus its name, derived from the Greek for “twisted chain.”
The primary classification method for clinically relevant streptococci is the Lancefield grouping system, developed in the 1930s. This system categorizes beta-hemolytic strains based on specific carbohydrate antigens in their cell walls, assigning them letter designations (e.g., Group A, B, C). This grouping is medically relevant because it often correlates with a specific pattern of disease, such as Group A Streptococcus (S. pyogenes) being distinct from Group B (S. agalactiae).
The bacteria possess various structural components that contribute to their ability to cause disease, known as virulence factors. In Group A Streptococcus, a fibrous protein called M protein projects from the cell surface. The M protein is a determinant of virulence, allowing the bacterium to resist phagocytosis by immune cells. The structure of this protein is also implicated in the development of certain severe post-infection complications.
Diverse Spectrum of Streptococcal Infections
The clinical manifestations of streptococcal infections vary widely depending on the species and site of infection. Streptococcus pyogenes (Group A Strep or GAS) is the most common cause of bacterial pharyngitis (strep throat), presenting with sudden sore throat, fever, and painful swallowing. Untreated GAS can lead to scarlet fever, characterized by a sandpaper-like rash resulting from streptococcal pyrogenic exotoxins.
Invasive GAS infections occur when the bacteria penetrate deep tissue layers. Necrotizing fasciitis (flesh-eating disease) is a rapidly progressing infection of the fascia and underlying muscle tissue that can lead to systemic shock and multi-organ failure. Streptococcal toxic shock syndrome is another severe condition marked by high fever, low blood pressure, and rapid progression to organ damage. S. pyogenes is typically transmitted through respiratory droplets.
A unique feature of GAS infection is the potential for non-suppurative, immune-mediated sequelae that develop weeks after the initial infection clears. Acute Rheumatic Fever (ARF) is a complication affecting the heart, joints, brain, and skin. Carditis can lead to permanent damage of the heart valves (Rheumatic Heart Disease). Post-Streptococcal Glomerulonephritis (PSGN) is an immune-complex disease causing inflammation of the kidney’s filtering units, leading to symptoms like swelling and dark urine.
Streptococcus agalactiae (Group B Strep or GBS) is primarily known for causing severe disease in newborns, where it is a leading cause of neonatal sepsis and meningitis. Early-Onset Disease (EOD) manifests within the first week of life, often as pneumonia and sepsis, acquired during passage through the birth canal. Late-Onset Disease (LOD) occurs in infants up to three months of age, often presenting as meningitis, acquired from outside sources after delivery.
Streptococcus pneumoniae (Pneumococcus) causes a range of respiratory and invasive diseases, transmitted via respiratory droplets. Noninvasive manifestations include acute otitis media (middle ear infection) and sinusitis. Invasive pneumococcal disease (IPD) includes community-acquired pneumonia, presenting with abrupt fever, chills, and a productive cough, and bacterial meningitis. IPD carries a significant risk of mortality, particularly in the very young, the elderly, and those with compromised immune systems.
Principles of Antibiotic Treatment
Treatment for most streptococcal infections relies heavily on antibiotics, with penicillins and related beta-lactam drugs serving as the first line of defense. Penicillin is highly effective because Streptococcus has not developed resistance to it through target modification. The drug is bactericidal, meaning it actively kills the bacteria.
The mechanism of action for beta-lactam antibiotics involves interfering with bacterial cell wall synthesis. These drugs bind to penicillin-binding proteins (PBPs), which are necessary for cross-linking the peptidoglycan chains that provide structural integrity. By inhibiting this process, the antibiotic causes the cell wall to weaken, leading to the bacterial cell bursting due to osmotic pressure.
Completing the full prescribed course of antibiotics, typically a 10-day regimen for penicillin, is necessary to ensure complete eradication of the organism. This prevents the risk of relapse and minimizes the chance of developing post-streptococcal sequelae like Acute Rheumatic Fever.
In patients with a penicillin allergy, alternative antibiotics are used. Macrolide antibiotics, such as azithromycin or clarithromycin, are common alternatives. First-generation cephalosporins, like cephalexin, are also alternatives for patients whose penicillin allergy is not severe. However, the reliance on these alternatives has contributed to an increase in macrolide resistance among some Streptococcus strains.
Mechanisms Driving Antibiotic Resistance
The development of antibiotic resistance poses a growing challenge, particularly in Streptococcus pneumoniae. This species develops resistance to beta-lactam antibiotics by altering the drug’s target structure rather than producing beta-lactamase. The bacterium achieves this by acquiring genetic material from closely related species, such as S. mitis and S. oralis, through genetic recombination.
This horizontal gene transfer results in a “mosaic” structure in the genes encoding the penicillin-binding proteins (PBPs): PBP1a, PBP2x, and PBP2b. The altered PBPs have a lower binding affinity for penicillin, preventing the drug from effectively blocking cell wall synthesis. High-level resistance is achieved through the cumulative effect of modifications in these three PBPs.
Macrolide Resistance Mechanisms
Macrolide resistance in Streptococcus species is driven by two main cellular mechanisms: efflux pumps and target site modification.
Efflux Pumps
This mechanism involves the acquisition of genes (e.g., mef(A) or mef(E)) that encode active efflux pumps. These membrane-bound proteins actively pump the macrolide antibiotic out of the bacterial cell before it can reach its target site.
Target Site Modification
This mechanism is mediated by erm genes (e.g., ermB or ermTR). These genes encode methylases that chemically modify the bacterial ribosome, the site where macrolides interfere with protein synthesis. This modification prevents the antibiotic from binding effectively, resulting in resistance to macrolides and sometimes other unrelated antibiotics (MLS resistance).
The widespread dissemination of these resistance genes is often facilitated by mobile genetic elements like plasmids, which are small, circular pieces of DNA transferred between bacteria. This horizontal gene transfer allows a single resistant bacterium to rapidly share its resistance traits, underscoring the need for continuous surveillance and judicious use of antibiotics.