Importance of strain lineages for Group B streptococcal survival

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is an encapsulated Gram-positive bacterium that commensally colonizes the lower gastrointestinal tract, and in females, the lower reproductive tract, of 20–30% of healthy adults. However, in immune compromised individuals, such as newborns, pregnant women, and the elderly, GBS may cause invasive disease including pneumonia, sepsis, urinary tract infections, and meningitis. The majority of newborn infection occurs within the first week of life and is designated early-onset disease, which includes pneumonia and respiratory failure, complicated by bloodstream infection and septicemia. In contrast to early-onset infection, lateonset GBS disease occurs in infants aged >1 week, who typically present with sepsis or pneumonia, and may contract meningitis, osteomyelitis, or septic arthritis. Over the last several decades in the United States, GBS has emerged as the leading cause of bacterial meningitis in the neonatal period; 25–50% of surviving infants are left with permanent neurologic sequelae including cognitive deficits, cerebral palsy, blindness, deafness or seizures. Whether in utero or during labor, neonatal exposure to GBS requires GBS survival, transversal through several host environments and barriers, immune evasion, and in the case of meningitis, crossing of the highly regulated blood–brain barrier. In the United States national guidelines were published in 2002 that focused on a single strategy of universal screening for GBS carriage of pregnant women at 35-37 weeks of gestation plus intrapartum antibiotic prophylaxis (IAP) for all women who are carriers. Despite the initial effectiveness of the antibiotic treatment in decreasing early onset GBS disease in 2002, the overall rate of early onset GBS disease has increased. Additionally, these strategies have not prevented late onset GBS neonatal sepsis and meningitis and there is increased concern of emerging patterns of antibiotic resistance in GBS and other organisms present during treatment. GBS is commonly classified into 10 antigenically distinct serotypes based on variation of the surface capsular polysaccharide (CPS), of which serotypes Ia, Ib, II, III, and V are more commonly associated with invasive disease. More recently GBS has also been classified by sequence type (ST) based on an allelic profile of 7 different loci, with the majority of GBS human isolates being ST-1, ST-17, ST-19, or ST-23. Interestingly there is a disproportionate burden of serotype III, ST-17 strains associated with neonatal invasive disease and meningitis. Further previous work has demonstrated that an ST-17 GBS strain was more likely to survive IAP, compared with an ST-12 strain. Thus the epidemiology of GBS infection suggests that variation in CPS and ST can lead to variable colonization and disease progression. In this issue of Virulence, the authors of the article entitled “Differing mechanisms of surviving phagosomal stress among group B Streptococcus strains of varying genotypes” examined how lineage difference may impact GBS tolerance to antibiotics and various stress conditions, as well as intracellular persistence in phagocytic cells. Phagocytic cells such as macrophages and neutrophils play an important role in innate immune defense against classic extracellular pathogens such as GBS. Pathogens that can persist within phagocytic cells and survive the phagolysosomal environment not only resistant phagocytic clearance, but may more readily disseminate into other bodily tissues. GBS survival within macrophage phagosmes has been reported, but the exact mechanism (s) and factors responsible are not well understood. The current study demonstrated that distinct GBS lineages differed in their ability to be phagocytized by and