Random Selection of Micro-oraginsm ; 7) Streptococcus agalactiae : cocci in chain
1) Streptococcus agalactiae :
S. agalactiae is the species designation for the only species of streptococci belonging to the group B of the Rebecca Lancefield classification of streptococci (Lancefield grouping). GBS is surrounded by a bacterial capsule composed of polysaccharides (exopolysacharide). The species is subclassified into ten serotypes (Ia, Ib, II–IX) depending on the immunologic reactivity of their polysaccharide capsule.This is why the plural term group B streptococci (referring to the serotypes) and the singular term group B streptococcus (referring to the single species) are both commonly encountered.
In general, GBS is a harmless commensal bacterium being part of the human microbiota colonizing the gastrointestinal and genitourinary tract of up to 30% of healthy human adults (asymptomatic carriers). Nevertheless, GBS can cause severe invasive infections especially in newborns, the elderly, and people with compromised immune systems
2) Classification :
Classification : ✓
Cellular organisms
Kingdom : Bacteria
Phylum : Firmicutes
Class : Bacilli
Order : Lactobacillales
Family : Streptococcaceae
Genus : Streptococcus
Species : Streptococcus agalactiae
Introduction :
Streptococcus is a genus that is classified based on the hemolytic properties into three types: Alpha-Hemolytic Streptococci, Beta-Hemolytic Streptococci, and Non-Hemolytic Streptococci.
Streptococcus agalactiae, often referred as Group B Streptococcus (GBS), is one of four Beta-Hemolytic streptococci, which results in complete rupture of blood cells shown in wide and clear areas surrounding bacterial colonies on blood agar.
a) Appearance: S. agalactiae is a diplococcal (a pair of cocci, circular, pair) gram-positive, non acid-fast bacterium (~2.0µm) that does not form spores, is not motile, and is catalase-free (catalase is an enzyme that catalyzes the reduction of hydrogen peroxide).
It occurs in pairs or short chains and has group B Lancefield antigen present.
b) Habitat: S. agalactiae , originally discovered as a cause of bovine mastitis, is part of the normal bacterial flora colonizing the gastrointestinal(GI) tract and genitourinary tract of a significant proportion of the human population.
However, it occasionally becomes an infectious pathogen colonizing the uterus, blood, brain, and meninges.
c) Significance : This pathogen is one of the leading causes of invasive infections in non-pregnant immunocompromised individuals and also causes bacteremia, septicaemia, meningitis, and pneumonia.
Colonization of the rectum and vagina of pregnant women with GBS is correlated with GBS sepsis in newborn infants with early onset disease.
S. agalactiae is also subclassified into nine serotypes depending on the immunologic reactivity of the polysaccharide capsule and among nine serotypes, only types Ia, Ib, II, III, and V are discovered to be responsible for invasive human disease.
d) Isolation: S. agalactiae can be isolated in infected sites of human or in secretions from infected mammary gland of female cattle and related ungulates. In some samples these bacteria are numerous and easily found in stained films; in other cases they may be so scarce that they can be located only with great difficulty. Also, most stains can be used to stain GBS to locate them, since the GBS is gram-positive and readily stained.
e) Genome project: S. agalactiae poses a serious threat to lives of neonates, responsible for 2-3 cases per 1000 live birth and to lives of human, especially elderly persons and those with weakened immune systems. This microorganism is considered one of the major causes of economic losses to dairy producers without a control program.
Because of its significance as an threat to both human and related ungulates, such as cow, its genome was sequenced and is still being studied to gain more insight into the virulence factor and to develop treatments and preventive prophylactic antibodies.
3) Ecology :
i) S. agalactiae colonizes in the body of some animals, including cow, sheep, and humans without causing any harm. The habitat of this microorganism is largely confined to the intestine and vagina in human and the mammary gland of cows and sheep.
ii) This microorganism also colonizes in the genital and/or intestinal tract of about 10-30% of pregnant women.However, some can actually cause diseases in their neonates or immunocompromised mammals.
iii) S. agalactiae is the common cause of inflammation or fibrosis of mammary glands and adjacent areas in cows and sheep colonizing the surface of the teat and duct sinuses.
iv) This species causes invasive bacterial infections in mostly neonates and rarely immunocompromised adults, most notably septicemia, pneumonia, and meningitis colonizing different locations including the faces, the nose, the umbilical cord, the ears, feces. Infection is spread between cows and/or sheep through the milker's hand, contaminated instrument, and the mouth of calves.
v) Once infected, these mammals are likely to lose their reproductive capacity due to blocked milk channels through inflammation.Infection in humans is through genital and/or intestinal tract of pregnant women either during pregnancy or delivery and from other neonates or members of the hospital staff in the maternity hospital.
vi) "The interaction of this bacteria with host protein and and the entry into host cells thereby represent important virulence traits."
vii) Since S.agalactiae is normally present in the vaginal and intestinal tract of 15-40% of adult women without causing any harm, the reason and mechanism of this microorganism causing diseases in neonates is still not fully known.
viii) However, neonates are thought to be infected by being exposed to this microorganism through the birth canal or by spread from the maternal genital tract before birth and during early neonatal period.
ix) Infections due to this microorganism can be divided into two types depending on when infections take a place in neonates. Most common early-onset infections take place before the end of the first week and less common late-onset between 1 week and 3 months after birth.
x) Experimental study of early-onset infection suggests that this bacteria to invade fetal epithelial and endothelial cells and certain macrophages and the mortality rates for early-onset is 4-6%. This invasion is confirmed to play important role in its pathogenesis through the ability of S. agalactiae in the monkey model.
xi) Ability to invade and transcytose, this bacteria can enter into the respiratory tract causing pneumonia or further into the blood causing septicemia. Bloodstream enables this bacteria to reach different sites of body causing meningitis and osteomyelitis. The little pathogenesis of late-onset infection is known.
xii) But it is suggested to be vertically transmitted from mother or horizontally transferred from nursery personnel. The mortality rate of this infections is relatively lower than that of early-onset infection, 2-6%. This infections is likely to cause meningtitis and bacteremia.
4) Cell Structure :
a) Cellular Features : S. agalactiae is a Gram-positive bacterium that is not motile, catalase-free, and diplococcal. It also does not form spores. (more information under appearance in description section).
Within its cell structures, S. agalactiae contains genes expressing various extracellular products, such as capsular polysaccharide and surface proteins. This bacteria seems to use those polysaccharide and surface proteins to adhere to epithelial cells of host and to evade host defense system.
b) Environment : Streptococcus agalactiae is host-associated facultative anaerobe, that is capable of using oxygen or not using oxygen depending on surrounding environment to generate ATP, aerobic respiration or fermentation, respectively. The optimal temperature for this species is at 37 Celcius (mesophile).
5) Metabolism :
a) Glucose Oxidation : (Oxidative phosphorylation) : S. agalactiae is a chemoorganotroph that uses glucose as energy source. This bacterium is able to synthesize ATP by oxidative phosphorylation.
Structural genes for cytochrome bd quinol oxidase and NADH dehydrogenase reveal the presence of enzymes contributing to aerobic growth of this species.
However, there was no gene discovered that is involved in heme synthesis suggesting possibility of using external source of heme, but no corresponding transporter was detected.
b) Fermentation : S. agalactiae is also able to ferment different carbon sources to multiple by-products, lactate, acetate, ethanol, formate or acetoin.
Interestingly, this bioenergetic mechanism is more related to that of non-pathogenic species under different genus, Lactococcus lactis than that of other pathogenic streptococci, shown in shown in genes coding for bd oxidase and some fermentation pathways containing orthologs in gene sequence of L. lactis.
c) Carbon Source : S. agalactiae is a heterotroph that is capable of importing a broad range of carbon sources. The genome sequence identified 17 sugar-specific phosphoenolpyruvate-dependent phosphotransferase system (PTS) enyzme II complex, revealing specificity for cellobioise, beta-glucoside, trehalose, mannose, lactose, fructose, mannitol, N-acetylgalactosamine, and glucose.
Also, four sugar-specific ABC transporter, three glycerol permeases and one glycerol-phosphate permease were found further confirming that S. agalaactiae is getting its carbon sources from various organic compounds.
Genes of S. agalactiae also code necessary enzymes for glycolysis and for pentose pathway involving pentose and gluconate utiliization, suggesting broad catabolic ability to live in various environment.
d) Amino Acid Biosynthesis : Despite of its ability given above, S. agalactiae is known to require a many amino acids in order to grow, due to the fact that it does not have any TCA cycle present to synthesize amino acids.
There are only few pathways to synthesize alanine, serine, glycine, glutamine, aspartate, asparagine, and threonine. Because S. agalactiae is an auxotroph, that requires additional nutrients, this bacteria needs mechanisms to import compounds from exogenous sources. Genes for eight ABC transporters and permeases specific for certain amino acids were identified and degradation of peptides by peptidases were also discovered to be used in import of amino acids.
Four genes encoding exported peptidase, three ABC transporters specific for oligopeptides, and 21 genes for intracellular peptidase revealed further confirmed uses of peptidase in recruiting amino acids.
e) Vitamin Biosynthesis : Mechanism for vitamin biosynthesis is not yet found.
Overall, there are various transporters playing roles in metabolism including two phosphate and two iron ABC tranpsorters and several cation transport systems.
This diversity seems to ensure that S. agalactiae' survival and multiplication in diverse environments, including various hosts, causing disease.
6) Pathogenicity :
i) Several factors are currently identified to increase the risk of infection, including rupture of cell membrane before labor and increased interval between rupture and delivery and it can also be affected by small amount of antibiotics against the virulence factor of S. agalactiae.
ii) Anticapsular vaccine, erythromycin, ampicillin, penicillin, cephalosporin, and vancomycin can be treated to prevent this infection. The pathogenesis for infections in adults are not yet known.
iii) S. agalactiae expresses several extracellular products including capsular polysaccharides, surface proteins and secreted proteins that are studied in some animal models (mouse,rat) to be the virulence factor (detail in pathogenic contents under genome section).
iv) When present, plasmid pIP501 in some strains of S. agalactiae confers antibiotic resistance also playing important role in pathogenesis.
v) The symptoms of different disease caused by this bacteria are as following. Symptoms of early onset neonatal septicemia includes lethargy, fever, jaundice, hypotension, hypothermia, tachypnea, bacteremia, and low Apgar scores.
vi) Symptom of early onset neonatal pneumonia includes low Apgar scores, lethargy fever, apnea, tachypnea, cyanosis, cough, pulmonary infiltrates, and rales. Symptoms of late-onset neonatal meningitis includes lethargy, fever, jaundice, hypotension, hypothermia, stiff neck, and rigidity seizures.
vii) Symptoms of osteomyelitis includes fever, bone pain, chills, erythema, swelling, and inflammation.
viii) Although Streptococcal diseases are very serious once developed, luckily only small percentage of neonates develop those even if their mother carry the bacteria (0.25 per 1000 lives with absence of clinical risk factors and 1-4 per 1000 birth with the presence of clinical risk factors).
ix) This microorganism is considered one of the major causes of economic losses to dairy producers without a control program and poses great threats to neonates and some populations of adult.
7) Genome : (interesting genome)
The genome of three strains of Streptococcus agalactiae (GBS) have been completely sequenced: S. agalactiae NEM 316, S. agalactiae 2603V/R, and S. agalactiae A909.
The genome of two plasmids also have been completely sequenced: S. agalactiae plasmid pGB3631 and S. agalactiae plasmid pGB354.
The genome of known five strains in S. agalactiae have not yet been completely sequenced: S. agalactiae 515, S. agalactiae CJB111, S. agalactiae COH1, S. agalactiae H36B, S. agalactiae 18RS21
b) Size of plasmid genome : Wild-type S. agalactiae plasmid pIP501 can be easily transferred and maintained in various S. agalactiae strains and confers antibiotic resistance to its recipients.
This plasmid pIP501 can be isolated from various strains of S. agalactiae and various Streptococci species, including S. sanguis and S. faecalis. This plasmid plays importance role in pathogenesis of those bacteria.
S. agalactiae plasmid pGB3631 is the deletion derivative of the wild-type S. agalactiae plasmid pIP501.
The complete genome sequence of this strain is a circular DNA chromosome with 5,842 nt (GC content of 33%, coding content of 62%) and contains 9 genes, 6 protein coding genes, no structural RNA, and no pseudogene. Genome sequence was completed in 1994.
S. agalactiae plasmid pGB354 is the derivative of the wild-type Streptococcus agalactiae plasmid pIP501.
Complete genome sequence of this strain is a circular DNA chromosome with 6,437 nt (GC content of 33%, coding content of 62%) and contains 5 genes, 5 protein coding genes, no structural RNA, and no pseudogene. Genome sequence was completed in 1997.
c) Pathogenic Contents : Analysis of NEM316 genome predicted and identified the loci responsible for extracellular products like capsular polysaccharide, surface proteins, and secreted proteins, which are involved in virulence and contributing to pathogenesis.
NEM 316 strain contains 17 genes (cpsA-L, neuBCDA) along with the transcriptional gene cpsY for sialyated capsular polysacchraide; 30 genes (gbs 0391, 0392, 0393, and 27 more genes) for surface proteins containing cell wall; and various genes responsible for 71 secreted proteins.
In genomic analysis of NEM315, it was also revealed to have stress adaption by encoding Clp proteins (gbs 1634, 1383, 1869, 1367, 0535), which are ATP-dependent proteases playing a role in virulence.
d) Interesting Features : The genome was analyzed to have several chromosomal islands, which is a unique feature different from other streptococci, but rather similar to pathogenic Escherichia coli .
This unexpected similarity built hypothesis that virulence factor was on the unique chromosomal island for both species and evolved them into pathogens. But this hypothesis was not yet tested.
Comparison of chromosomal order of genes of S. agalactiae with that of other pathogenic streptococci, S. pyogenes and S. pneumoniae showed that it was highly conserved between S. agalactiae and S. pyogenes than between S. agalactiae and S. pneumoniae revealing higher relatedness between S. agalactiae and S. pyogenes.
Also, some pathogenicity islands discovered in genes of S. agalactiae were unique to this bacteria and it seems to be diverse between different strains of S. agalactiae.
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