See also Scarlet Fever
Introduction:
Streptococcus pyogenes (Group A Streptococcus) is is the etiologic agent responsible for many conditions related to streptococcal infections. It is more commonly known as Group A Strep and has more than 6,000 recognized subtypes, with new strains constantly arising. The most common form of infection involves a colonization of the pharyrix known as strep throat. cause pharyngitis, scarlet fever, and toxic shock.
S. pyogenes (Group A Streptococcus pyorgenes (GAS)) is a beta-hemolytic human selective pathogen that is responsible for a large number of morbid and mortal infections in humans. For efficient infection, it requries different types of surface proteins that provide various mechanisms for evading human innate immune responses. It is responsible for about 700 million infections per year of the throat and skin. These infections are usually self-limiting, and the bacteria are cleared by penicillin type antibiotics. However, some strains of GAS are highly virulent and invade deep tissue sites, casuing diseases such as necrotizing faciitis and toxic shock syndrom with multiple organ failure. (Castellino, “The M protein of Streptococcus pyogenes Strain AP53 retains cell surface functional plasminogen binding after inactivaiton of the sortase A gene” J. Bacteriology, 2020).
A life-threatening invasive version of strep Group A — which can include deep-rooted skin infections, sepsis, meningitis and deadly pneumonia — is on the rise around the world. In the U.S., there have been more than double the annual incidents of invasive Group A strep in 10 states, affecting about 35 million Americans between 2013 and 2022, with 21,000 cases and about 2,000 deaths
Biochemical and Morphological Characteristics
They tend to be short chains in clinical samples with longer chains in liquid media. They are beta hemolytic and contain an outer capsule. In the pre-antibiotic era severe infections due to group A ß-haemolytic streptococcus were major causes of morbidity and mortality.
Diagnosis and Symptoms
The clinical features of group A sreptococcal pneumonia include sudden high fever, pleuritic chest pain, chills, caugh, sputum and dyspnoea. The most typical feature suggesting the diagnosis of group A streptococcal pneumonia is the rapid accumulation of a plueral effusion. In view of the emergence of more virulent group A streptococcal infections, it is important to initiate early and appropriate antibiotic therapy for common uncomplicated streptococcal infections such as pharyngitis, tonsillitis, impetigo and cellulitis.
Mechanisms of pathology:
Secretion of Enzymes:
–-Endoglycosidases: S. pyogenes secretes two enzymes shwoing remarkable specificity for IgG; EndoS and IdeS.
(i) EndoS efficiently and specifically hydrolyzes the functionally important N-linked glycan of IgG and treatment with EndoS abrogates the pathogenic activity of IgG in mouse models of autoimmune disease.
(ii) IdeS or streptococcal Mac-1 is a secreted cysteine proteinase that specifically cleaves the heavy chain of IgG. Due to its early and sustained expression during growth and its highly specific proteolytic activity, IdeS is a tailor-made defense against Fc mediated phagocytic killing. In one study, the enzyme was found to block the development of IgG-induced arthritis. Johansson (“IdeS: a bacterial proteolytic enzyme with therapeutic potential” 2008) showed that this enzyme in vitro efficiently cleaves IgG in human whole blood, removes IgG from the blood circulation of rabbits without any side effices and cures mice from lethal IgG induced thrombocytopenia.
Horizontal Gene Transfer:
Transformation, conjugation, and transduction are common means of genetic exchange in bacteria. In S. pyogenes, natural transformation may occur when the cells live in a biofilm, but such exchange has not been seen under typical laboratory conditions. Conjugative transposons are frequent elements in S. pyogenes, but they are not associated with transfer events seen with the F plasmid of E. coli. Generalized transduction, by contrast, occurs in S. pyogenes and is mediated by both lytic and lysogenic phages.
Transduction:
Transduction may play a role in the dissemination of genes among related streptococcal species. Some bacteriophages isolated from groups A and G streptococci can infect serotype A, C, G, H, and L strains; some were capable of infecting multiple serotypes.
Bacteriophages typically may be grouped by their life cycle into two categories: lytic phages and lysogenic (temperate) phages. Lytic phages infect their host cell and begin the viral replicative cycle within a short time frame. At the end of replication and assembly, the host bacterial cell typically lyses and releases the newly formed bacteriophage particles.
The bacteriophages of Streptococcus pyogenes (group A streptococcus) play a key role in population shaping, genetic transfer, and virulence of this bacterial pathogen. Lytic phages like A25 can alter population distributions through elimination of susceptible serotypes but also serve as key mediators for genetic transfer of virulence genes and antibiotic resistance via generalized transduction. The sequencing of multiple S. pyogenes genomes has uncovered a large and diverse population of endogenous prophages that are vectors for toxins and other virulence factors and occupy multiple attachment sites in the bacterial genomes. See Nguyen
Lysogenic bacteriophages of S. pyogenes are capable of mediating transfer of antibiotic resistance by transduction. Strains with bacteriophage T12-like prophages can produce transducing lysates capable of transferring resistance to tetracycline, chloramphenicol, macrolides, lincomycin, and clindamycin following lysogen induction. Generalized transduction transfer of erythromycin and streptomycin resistance following mitomycin C treatment of endogenous prophages has also been observed.
Lysogenic bacteriophages are defined by their ability to integrate their DNA into the host bacterium’s chromosome via site-specific recombination, becoming a stable genetic element that can be passed to daughter cells following cell division. Minimally, lysogeny requires genes encoding an integrase (recombinase) and excisionase to mediate prophage DNA integration and excision as well as genes encoding repressor and antirepressor proteins to direct and control this process following the pattern seen in coliphage Lambda. Phage integrases typically mediate a recombination event between an identical sequence shared between the circular form of the prophage genome (attP) and the bacterial chromosome (attB), and the recognition of these DNA sequences is inherent in a given integrase protein.
About 90% of the isolates of S. pyogenes are lysogenic, due to complete or partial prophages integrated into the host chromosome that sometimes contribute up to 12% of the total genome. Transformation appears to play no or only a minor role in lateral DNA transfer in S. pyogenes, conferring on phages a special role in this process. It has been suggested that in this species competence and transformation may have been lost due to the growing role assumed by bacteriophages in population diversity. These S. pyogenes phages or phage-like elements have long been known to encode many virulence factors, but more recently they have also been shown to carry antibiotic resistance genes. See Varaldo