Streptococcus

• 1. Introduction

  ›

  Streptococcus is a genus of bacteria whose name is built from two Ancient Greek words: streptós, meaning "twisted", and kókkos, meaning "grain". That name was coined in 1877 by a Viennese surgeon named Albert Theodor Billroth, who noticed something peculiar under the microscope. These bacteria, when dividing, split along a single axis only. The result is long, twisted chains of rounded cells, rather than the grape-like clumps made by their relatives the staphylococci. That one structural difference, invisible to the naked eye, turns out to carry enormous consequences for human health.

  Today, over 50 species are recognised in this genus. Some of them live quietly in our mouths, skin, intestines, and upper respiratory tracts as harmless residents. Others are among the world's most dangerous pathogens, responsible for strep throat, meningitis, necrotizing fasciitis, and more than 500,000 deaths globally every year. And one species, Streptococcus thermophilus, is the bacterium that helps make Swiss cheese and yogurt. The questions this documentary will explore: how do scientists sort through this enormous and diverse genus, how does the same family of bacteria include both helpful kitchen partners and flesh-eating killers, and what tools does medicine use to fight back?

• 2. A Name and Its Family Tree

  ›

  Albert Theodor Billroth lived from 1829 to 1894, and when he named Streptococcus in 1877, the field of bacteriology was still young. The genus he identified would eventually be placed within the order Lactobacillales, the lactic acid bacteria, inside the phylum Bacillota. These are gram-positive bacteria, meaning their cell walls stain a characteristic colour in the standard laboratory test that bears the name of scientist Hans Christian Gram.

  For over a century, the genus grew in an unruly fashion, accumulating species that were merely similar in appearance. Then, in 1984, scientists conducted a major reclassification. Many organisms previously called streptococci were split off into two new genera: Enterococcus and Lactococcus. That reorganisation was a turning point, leaving Streptococcus as a tighter and more coherent group.

  Molecular tools have since allowed researchers to map the genus in far finer detail. By analysing 16S rDNA sequences, scientists divided streptococci into six major groups, named after representative species: S. anginosus, S. gallolyticus, S. mitis, S. mutans, S. pyogenes, and S. salivarius. Whole genome sequencing later confirmed those groupings. Then, in 2018, researchers Patel and Gupta conducted a deeper analysis. They built comprehensive phylogenetic trees from four different protein datasets and identified 134 highly specific molecular signatures, in the form of conserved signature indels, shared across the genus or its subgroups. Their work revealed two major clades at the highest level: the "Mitis-Suis" clade and the "Pyogenes-Equinus-Mutans" clade, with 14 distinct subclades identified in total. Each subclade is supported by reliable branching patterns and by the presence of multiple conserved signatures in different proteins.

• 3. Reading Blood: The Clinical Toolkit

  ›

  Rebecca Lancefield was a scientist at Rockefeller University, and her system of classification remains the backbone of clinical streptococcal diagnosis today. Her insight was to group beta-hemolytic streptococci by the specific carbohydrates present on their cell walls. The result is a set of 21 described serotypes, named Lancefield groups A through W, excluding E, I, and J.

  Before Lancefield grouping, however, the first thing a clinical microbiologist does with a streptococcal sample is to check its hemolytic properties, meaning how it behaves when grown on blood agar. Alpha-hemolytic species oxidise the iron in hemoglobin, turning the agar a dark greenish colour. Beta-hemolytic species go further: they completely rupture red blood cells, leaving clear, transparent halos around bacterial colonies. Gamma-hemolytic species cause no visible change at all.

  The enzyme responsible for beta-hemolysis is streptolysin, and it comes in two forms. Streptolysin O is oxygen-sensitive and interacts with cholesterol in the membranes of red blood cells, white blood cells, macrophages, and platelets. Streptolysin S is oxygen-stable and affects polymorphonuclear leukocytes and lymphocytes. Streptolysin S is thought to actively suppress the host immune system's ability to clear the infection. Beyond hemolysis and Lancefield grouping, quick bench tests such as the PYR test for group A streptococcus, and latex agglutination kits, allow clinicians to narrow down the specific species involved without elaborate laboratory infrastructure.

• 4. Group A: From Sore Throats to Flesh-Eating Disease

  ›

  Streptococcus pyogenes, known as Group A Streptococcus or GAS, causes the widest range of infections within this genus. On the milder end sit streptococcal pharyngitis, commonly called strep throat, and impetigo. Scarlet fever also falls in this noninvasive category. These infections are more common and generally less severe, though still requiring treatment.

  When GAS invades areas of the body it does not normally inhabit, such as the blood and organs, the consequences can be severe. Streptococcal toxic shock syndrome, necrotizing fasciitis, pneumonia, and bacteremia all belong to this invasive category. Globally, GAS has been estimated to cause more than 500,000 deaths every year.

  The bacterium's dangers do not end with the acute infection. Two serious complications can follow an untreated strep A infection: acute rheumatic fever and acute glomerulonephritis. Rheumatic fever affects the joints, kidneys, and heart valves, but not through any direct action by the bacterium. Instead, antibodies the immune system produces to fight off the infection cross-react with proteins in the body's own tissues, causing the immune system to attack itself. A related autoimmune mechanism, triggered by Group A beta-hemolytic streptococcal infection, is hypothesised to cause a condition called PANDAS, or pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. In PANDAS, autoimmune antibodies are thought to affect the basal ganglia, producing rapid onset of psychiatric, motor, sleep, and other symptoms in pediatric patients. GAS infection is generally confirmed with a rapid strep test or by culture.

• 5. Group B and the Newborn Risk

  ›

  Streptococcus agalactiae, the Group B Streptococcus or GBS, presents a particular danger at the beginning of life. It is the most common cause of meningitis in infants from one month to three months old. It can also cause pneumonia and meningitis in the elderly, along with occasional bacteremia in adults.

  The bacterium's ability to colonise the female reproductive tract is central to its threat to newborns. That colonisation can increase the risk of premature rupture of membranes during pregnancy, and it creates a route for the organism to reach the infant at birth. Three major American medical bodies, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control, all recommend that pregnant women be tested for GBS between 35 and 37 weeks of gestation. Women who test positive should receive prophylactic antibiotics during labour. Group III polysaccharide vaccines have also been proven effective at preventing the transmission of GBS from mother to infant.

  The United Kingdom takes a different approach, using a risk factor-based protocol rather than routine culture testing. Under current UK guidelines, a woman should receive intrapartum antibiotics if she has any one of several specified risk factors, including GBS in her urine during the current pregnancy, a previous infant with GBS disease, a fever of 38 degrees Celsius or higher during labour, preterm labour before 37 weeks, or membrane rupture lasting more than 18 hours. This protocol results in antibiotics being given to between 15 and 20 percent of pregnant women, and it prevents between 65 and 70 percent of cases of early-onset GBS sepsis.

• 6. Animals, Zoonoses, and the Wider World

  ›

  Streptococcus does not restrict itself to human hosts. Group C includes S. equi, which causes a horse disease called strangles, and S. zooepidemicus, from which S. equi descended as a clonal variant. S. zooepidemicus infects several species of mammals, including cattle and horses. Group C streptococcal bacteria are classified as zoonotic pathogens, meaning infection can cross from animal to human.

  Group G streptococci are also zoonotic. Among them, S. phocae has been found in marine mammals and marine fish. In marine mammals it has been associated mainly with meningoencephalitis, sepsis, and endocarditis, though many other pathologies have also been documented. Its environmental reservoir and route of transmission in marine mammals remain poorly understood.

  Group H streptococci occupy a different niche: they cause infections in medium-sized canines, and they rarely cause illness in humans unless there is direct mouth-to-mouth contact with an infected dog. Even a dog licking a human hand can provide a transmission route. S. suis, a member of the non-enterococcal group D streptococci, causes meningitis in swine. S. equi, to remain in group C, causes the same "strangles" condition in horses that was mentioned above, while its ancestor S. zooepidemicus spreads across a broader range of mammalian hosts. The genus also finds a role in the food industry: S. thermophilus is used in the production of Emmentaler, the cheese commonly known as Swiss cheese, as well as yogurt.

• 7. Genomes, Phages, and Transformation

  ›

  Most Streptococcus genomes fall in the range of 1.8 to 2.3 megabases in size and encode between 1,700 and 2,300 proteins. Four species whose genomes have been fully characterised illustrate the scale of variation. S. pyogenes has 1,852,442 base pairs and 1,792 open reading frames. S. agalactiae has 2,211,488 base pairs and 2,118 open reading frames. S. pneumoniae has 2,160,837 base pairs and 2,236 open reading frames. S. mutans has 2,030,921 base pairs and 1,963 open reading frames. Despite belonging to the same genus, these four species share an average pairwise protein sequence identity of only about 70 percent. Notably, S. pyogenes carries prophages, while the other three in this comparison do not.

  Viruses that infect bacteria, known as bacteriophages, have been documented across many streptococcal species. In S. pneumoniae alone, 18 prophages have been described, ranging from 38 to 41 kilobases and encoding between 42 and 66 genes each. Among the earliest known streptococcal phages are Dp-1 and omega-1. In 1981, the Cp family, officially named Streptococcus virus Cp1, was discovered, with Cp-1 as its founding member. Both Dp-1 and Cp-1 are capable of infecting both S. pneumoniae and S. mitis.

  The genetic flexibility of streptococci extends further still through a process called natural transformation, in which DNA is taken up from the surrounding environment and incorporated into the bacterial genome. S. pneumoniae, S. mitis, and S. oralis can all enter a special physiological state called competence, which enables this process. Among highly competent isolates of S. pneumoniae, research by Li and colleagues showed that both nasal colonisation fitness and lung infectivity depend on an intact competence system. Competence may allow the pathogen to use external DNA for recombinational repair of damage caused by the host's oxidative attack, giving the bacterium one more tool to survive inside us.