Streptococcus agalactiae: An Overview of the Group B Streptococcus
Streptococcus agalactiae, universally known as Group B Streptococcus (GBS), is a significant human pathogen and a member of the *Streptococcus* genus. It is characterized as a Gram-positive coccus, meaning it is a round bacterium that stains purple in the Gram stain test. These cells typically form pairs or chains of varying lengths, a characteristic reflected in its genus name. Physiologically, *S. agalactiae* is a facultative anaerobe, capable of growth in both the presence and absence of oxygen, and it is catalase-negative and non-spore-forming. It is primarily identified by its possession of the Group B antigen in its cell wall, as defined by the Rebecca Lancefield classification system, and its characteristic narrow zone of beta-hemolysis when grown on blood agar plates.
Despite being a major causative agent of severe invasive infections, GBS commonly exists as a harmless commensal organism. It is a normal component of the human microbiota, colonizing the gastrointestinal and genitourinary tracts, including the rectum and vagina, of up to 30% of healthy adults, who are considered asymptomatic carriers. In fact, GBS was first identified as a veterinary pathogen, a frequent source of bovine mastitis in dairy cows, before its recognition in the 1960s as a major human pathogen. Its classification as a pathobiont highlights its unique ability to switch from a state of asymptomatic mucosal carriage to causing life-threatening invasive disease, particularly in high-risk populations.
Biological Structure, Serotypes, and Metabolism
The morphology of *S. agalactiae* typically consists of spherical or ovoid cocci, ranging from 0.5 to 1.2 µm in diameter, arranged in chains that may be quite long in fluid cultures. A key structural feature is the presence of a polysaccharide capsule, which surrounds the bacterium. This capsule is the basis for its subclassification into ten distinct serotypes (Ia, Ib, II, III, IV, V, VI, VII, VIII, and IX, with serotype IX being identified later in 2007). The type-specific capsular polysaccharides are crucial virulence factors, as they enable the bacterium to evade the host’s immune system by inhibiting the activation of the alternative complement cascade and preventing phagocytosis, contributing significantly to differences in virulence potential among strains.
Biochemically, GBS exhibits several key reactions that aid in its identification. It is negative for the catalase, oxidase, citrate, and urease tests. It is positive for the fermentation of common carbohydrates such as glucose, fructose, galactose, lactose, and maltose, but typically negative for mannitol, mannose, and raffinose. A definitive test is the CAMP test, which is characteristically positive: GBS gives an enhanced, arrowhead-shaped zone of beta-hemolysis at the juncture where it is streaked perpendicular to a strain of *Staphylococcus aureus* on a blood agar plate. Furthermore, *S. agalactiae* is resistant to the antibiotic bacitracin, which helps to differentiate it from *Streptococcus pyogenes* (Group A Streptococcus), which is bacitracin sensitive.
Major Virulence Factors and Pathogenesis
The ability of *S. agalactiae* to cause invasive disease is mediated by an array of virulence factors. The most critical is the aforementioned capsular polysaccharide, which shields the bacterium from immunological detection. Another highly important factor is Beta-hemolysin/Cytolysin, a pore-forming toxin. This toxin is able to lyse host cells, including pulmonary alveolar epithelial and endothelial cells, playing a significant role in neonatal lung infection and subsequent sepsis. The bacteria also produce C5a peptidase, an enzyme that cleaves the complement component C5a, thereby interfering with neutrophil chemotaxis and limiting the body’s inflammatory response. Other factors, such as lipoteichoic acid, participate in facilitating adherence to host tissues, an essential first step in the infection process, while various cell surface proteins may mediate internalization of the organisms within human epithelial cells and protect them from intracellular killing by phagocytes.
Invasive Disease in Neonates: Early-Onset and Late-Onset
GBS is globally recognized as the leading cause of severe bacterial neonatal infection, including sepsis, pneumonia, and meningitis, with significant morbidity and mortality, especially in premature infants. Neonatal infections are clinically separated into two syndromes: early-onset disease (EOD) and late-onset disease (LOD). EOD typically manifests within the first 7 days of life, with the majority of cases becoming apparent within 24 hours of birth. EOD is acquired vertically, meaning the fetus or baby is exposed to GBS from the mother’s colonized vaginal or gastrointestinal tract, either *in utero* (after premature or prolonged rupture of membranes) or during passage through the birth canal. The most common manifestations of EOD are sepsis without an apparent focus and pneumonia, with meningitis occurring less frequently.
In contrast, LOD occurs from 7 days up to 3 months after birth, with a mean onset around 3 to 4 weeks. LOD may be acquired postnatally from the mother, other caregivers, or nosocomially (in a healthcare setting), though acquisition from the birth canal of a colonized mother is also a factor. Meningitis is a more common clinical syndrome in LOD, accounting for approximately 25% of cases. Despite appropriate treatment, neonatal GBS infections carry a high risk of death, particularly in older infants, and long-term neurological sequelae in survivors, emphasizing the critical burden of this disease.
GBS Infection in Pregnant and Non-Pregnant Adults
While the focus is often on neonatal disease, GBS is also an important pathogen in adults, especially in pregnant women and immunocompromised individuals. In pregnant women, GBS colonization usually presents no symptoms; however, it can lead to complications such as chorioamnionitis (infection of the placental tissues), postpartum infections, and urinary tract infections (UTIs) which are sometimes associated with the induction of premature labor and delivery. In the wider adult population, the burden of GBS disease is increasing, particularly among the elderly and those with underlying medical conditions like diabetes mellitus, cancer, and HIV.
In non-pregnant adults, the most common clinical syndromes of invasive GBS disease are bacteremia without an apparent focus and skin and soft-tissue infections, which may present as cellulitis, abscesses, or foot infections, with diabetes being a frequent predisposing factor. GBS bacteremia can also lead to focal infections such as pneumonia, osteomyelitis (bone infection), and endocarditis (infection of the heart valves). GBS endocarditis, though less common now than historically, remains a serious condition associated with high mortality rates, and cases have been described in both structurally normal and abnormal hearts.
Prevention and Treatment Strategies
The primary strategy for managing and preventing neonatal GBS infection in developed nations is the implementation of universal maternal screening and intrapartum antibiotic prophylaxis (IAP). This involves screening pregnant women for GBS rectovaginal colonization late in pregnancy (typically at 35–37 weeks) and administering intravenous penicillin G (the mainstay of therapy) to colonized mothers during labor. This intervention has successfully reduced the incidence of EOD. However, IAP has not had a significant impact on the incidence of LOD, highlighting the need for broader preventive measures.
A growing concern is the increasing frequency of antibiotic resistance. While penicillin G remains the drug of choice, reduced penicillin susceptibility has been observed in select isolates. Furthermore, resistance to non-beta-lactam antibiotics, including macrolides and clindamycin, has been observed, and strains resistant to vancomycin, a potent last-resort antibiotic, have also been detected. Currently, no human vaccine is available, making the development and implementation of a GBS vaccine a critical public health goal to significantly reduce the global burden of this continuing and severe pathogen.