| Streptococcus pneumoniae | |
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| S. pneumoniae in spinal fluid. FA stain (digitally colored). | |
Scientific classification | |
| Domain: | Bacteria |
| Kingdom: | Bacillati |
| Phylum: | Bacillota |
| Class: | Bacilli |
| Order: | Lactobacillales |
| Family: | Streptococcaceae |
| Genus: | Streptococcus |
| Species: | S. pneumoniae |
| Binomial name | |
| Streptococcus pneumoniae (Klein 1884) Chester 1901 | |
Streptococcus pneumoniae, orpneumococcus, is aGram-positive, spherical bacteria,alpha-hemolytic member of thegenusStreptococcus.[1]S. pneumoniae cells are usually found in pairs (diplococci) and do not formspores and are non motile.[2] As a significant humanpathogenic bacteriumS. pneumoniae was recognized as a major cause ofpneumonia in the late 19th century, and is the subject of manyhumoral immunity studies.[citation needed]
Streptococcus pneumoniae resides asymptomatically in healthy carriers typically colonizing the respiratory tract, sinuses, andnasal cavity. However, in susceptible individuals withweaker immune systems, such as the elderly and young children, the bacterium may becomepathogenic and spread to other locations to cause disease. It spreads by direct person-to-person contact viarespiratory droplets and by auto inoculation in persons carrying the bacteria in their upper respiratory tracts.[3] It can be a cause ofneonatal infections.[4]
Streptococcus pneumoniae is the main cause ofcommunity acquired pneumonia andmeningitis in children and the elderly,[5] and ofsepsis in those infected withHIV. The organism also causes many types ofpneumococcal infections other thanpneumonia. These invasive pneumococcal diseases includebronchitis,rhinitis,acute sinusitis,otitis media,conjunctivitis,meningitis, sepsis,osteomyelitis,septic arthritis,endocarditis,peritonitis,pericarditis,cellulitis, andbrain abscess.[6]
Streptococcus pneumoniae can be differentiated from theviridans streptococci, some of which are alsoalpha-hemolytic, using anoptochin test, asS. pneumoniae is optochin-sensitive.S. pneumoniae can also be distinguished based on its sensitivity tolysis bybile, the so-called "bile solubility test". Theencapsulated, Gram-positive,coccoid bacteria have a distinctive morphology on Gram stain,lancet-shaped diplococci. They have apolysaccharide capsule that acts as avirulence factor for the organism; more than 100 differentserotypes are known[7], and these types differ invirulence,prevalence, and extent ofdrug resistance.
The capsular polysaccharide (CPS) serves as a critical defense mechanism against the host immune system. It composes the outermost layer of encapsulated strains ofS. pneumoniae and is commonly attached to the peptidoglycan of the cell wall.[8] It consists of a viscous substance derived from a high-molecular-weight polymer composed of repeating oligosaccharide units linked by covalent bonds to the cell wall. The virulence and invasiveness of various strains ofS. pneumoniae vary according to their serotypes, determined by their chemical composition and the quantity of CPS they produce. Variations among differentS. pneumoniae strains significantly influencepathogenesis, determining bacterial survival and likelihood of causing invasive disease.[9] Additionally, the CPS inhibitsphagocytosis by preventinggranulocytes' access to the cell wall.[10]
In 1881, the organism, known later in 1886 as the pneumococcus[11] for its role as a cause of pneumonia, was first isolated simultaneously and independently by the U.S. ArmyphysicianGeorge Sternberg[12] and the French chemistLouis Pasteur.[13]
The organism was termedDiplococcus pneumoniae from 1920[14] because of its characteristic appearance inGram-stainedsputum. It was renamedStreptococcus pneumoniae in 1974 because it was very similar tostreptococci.[11][15]
Streptococcus pneumoniae played a central role in demonstrating that genetic material consists ofDNA. In 1928,Frederick Griffith demonstratedtransformation of life turning harmless pneumococcus into a lethal form by co-inoculating the live pneumococci into a mouse along with heat-killedvirulent pneumococci.[16] In 1944,Oswald Avery,Colin MacLeod, andMaclyn McCarty demonstrated that the transforming factor inGriffith's experiment was notprotein, as was widely believed at the time, but DNA.[17] Avery's work marked the birth of themolecular era of genetics.[18]
Thegenome ofS. pneumoniae is a closed, circular DNA structure that contains between 2.0 and 2.1 millionbase pairs depending on thestrain. It has a core set of 1553genes, plus 154 genes in itsvirulome, which contribute to virulence and 176 genes that maintain a noninvasivephenotype. Genetic information can vary up to 10% between strains.[19] The pneumococcal genome is known to contain a large and diverse repertoire of antimicrobial peptides, including 11 differentlantibiotics.[20]
Natural bacterial transformation involves the transfer of DNA from one bacterium to another through the surrounding medium. Transformation is a complex developmental process requiringenergy and is dependent on expression of numerous genes. InS. pneumoniae, at least 23 genes are required for transformation. For a bacterium to bind, take up, and recombineexogenous DNA into itschromosome, it must enter a special physiological state calledcompetence.[21]Competence inS. pneumoniae is induced by DNA-damaging agents such asmitomycin C,fluoroquinoloneantibiotics (norfloxacin,levofloxacin andmoxifloxacin), andtopoisomerase inhibitors.[22] Transformation protectsS. pneumoniae against the bactericidal effect of mitomycin C.[23] Michod et al.[24] summarized evidence that induction of competence inS. pneumoniae is associated with increased resistance tooxidative stress and increased expression of the RecA protein, a key component of therecombinational repair machinery for removingDNA damage. On the basis of these findings, they suggested that transformation is an adaptation for repairing oxidative DNA damage.S. pneumoniae infection stimulatespolymorphonuclear leukocytes (granulocytes) to produce an oxidative burst that is potentially lethal to the bacteria. The ability ofS. pneumoniae to repair oxidative DNA damage in its genome caused by this host defense likely contributes to the pathogen's virulence. Consistent with this premise, Li et al.[25] reported that, among different highly transformableS. pneumoniae isolates, nasal colonization fitness and virulence (lung infectivity) depend on an intact competence system.
Streptococcus pneumoniae is part of the normalupper respiratory tractflora. As with many natural flora, it can become pathogenic under the right conditions, typically when the immune system of the host issuppressed.Invasins, such aspneumolysin, an antiphagocyticcapsule, variousadhesins, andimmunogeniccell wall components are all majorvirulence factors. AfterS. pneumoniae colonizes theair sacs of thelungs, the body responds by stimulating the inflammatory response, causing plasma, blood, and white blood cells to fill the alveoli. This condition is called bacterial pneumonia.[26]
S. pneumoniae undergoes spontaneousphase variation, changing between transparent and opaque colony phenotypes. The transparent phenotype has a thinner capsule and expresses large amounts of phosphorylcholine (ChoP) and choline-binding protein A (CbpA), contributing to the bacteria's ability to adhere and colonize in the nasopharynx.[27] The opaque phenotype is characterized by a thicker capsule, resulting in increased resistance to host clearance.[27] It expresses large amounts of capsule and pneumococcal surface protein A (PspA) which help the bacteria survive in the blood.[28] Phase-variation between these two phenotypes allowsS. pneumoniae to survive in different human body systems.
Pneumonia is the most prevalent disease caused byStreptococcus pneumoniae. Pneumonia is a lung infection characterized by symptoms such as fever, chills, coughing, rapid or labored breathing, and chest pain.[29] For the elderly, those who contract pneumonia have also shown these lesser nonspecific symptoms, but also tend to show that they have tachypnea a few days before clinical certainty that they have contracted the bacterial illness. Tachypnea is characterized by rapid and shallow breathing and can affect a person's ability to sleep, chest pain, and a decreased appetite.[30]
While a few different bacterial infections can lead to meningitis, S. pneumoniae is one of the leading causes of this infection. Pneumococcal meningitis occurs when the bacteria goes from the blood to the central nervous system, which is made up of the brain and the spinal cord. Here, the infection will spread and cause inflammation, leading to severe disabilities like brain damage or hearing loss or limb removal or death.[31] Symptoms include common problems such as head aches, fevers, and nausea, but the more telling signs that a bacterial infection may have reached the brain are sensitivity to light, seizures, having limited range in neck movement, and easy bruising all over the body.
Osteomyelitis, or bone infection, is a rare occurrence but has been seen in patients who were diagnosed to have a S. pneumoniae infection that went untreated for too long.[32]
Sepsis is caused by overwhelming response to an infection and leads to tissue damage,organ failure, and even death. The symptoms include confusion, shortness of breath, elevated heart rate, pain or discomfort, over-perspiration, fever, shivering, or feeling cold.[33][34]
Less severe illnesses that can be caused by pneumococcal infection are conjunctivitis (pink eye ), otitis media (middle ear infection), Bronchitis (airway inflammation), and sinusitis (sinus infection).[35]
Due to the importance of disease caused byS. pneumoniae, severalvaccines have been developed to protect against invasive infection. TheWorld Health Organization recommends routine childhood pneumococcal vaccination;[36] it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom,[37] the United States,[38] Greece,[39]and South Africa.[40]
Currently, there are two vaccines available for S. pneumoniae: the pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccine (PCV13). PPV23 functions by utilizing CPS to stimulate the production of type-specific antibodies, initiating processes such as complement activation, opsonization, and phagocytosis to combat bacterial infections. It elicits a humoral immune response targeting the CPS present on the bacterial surface.[41] PPSV23 offersT-cell-independent immunity and requires revaccination 5 years after the first vaccination because of its temporary nature.[42] PCV13 was developed when determining its low efficacy in children and infants. PCV13 elicits a T-cell-dependent response and provides enduring immunity by promoting interaction betweenB and T cells, leading to an enhanced and prolonged immune response.[42]
Components fromS. pneumoniae have been harnessed for a range of applications in biotechnology. Through engineering of surface molecules from this bacterium, proteins can be irreversibly linked using thesortase enzyme[43] or using the SnoopTag/SnoopCatcher reaction.[44] Variousglycoside hydrolases have also been cloned fromS. pneumoniae to help analysis of cellglycosylation.[45]
Historically,Haemophilus influenzae has been a significant cause of infection, and bothH. influenzae andS. pneumoniae can be found in the human upper respiratory system. A study of competitionin vitro revealedS. pneumoniae overpoweredH. influenzae by attacking it withhydrogen peroxide.[46] There is also evidence thatS. pneumoniae uses hydrogen peroxide as a virulence factor.[47] However, in a study adding both bacteria to thenasal cavity of amouse within two weeks, onlyH. influenzae survives; further analysis showed thatneutrophils (a type of phagocyte) exposed to deadH. influenzae were more aggressive in attackingS. pneumoniae.[48]
Diagnosis is generally made based on clinical suspicion along with a positive culture from a sample from virtually any place in the body.S. pneumoniae is, in general,optochin sensitive, although optochin resistance has been observed.[49]
The recent advances in next-generation sequencing andcomparative genomics have enabled the development of robust and reliable molecular methods for the detection and identification ofS. pneumoniae. For instance, theXisco gene was recently described as a biomarker for PCR-based detection ofS. pneumoniae and differentiation from closely related species.[50]
Atromentin and leucomelone possess antibacterial activity, inhibiting theenzymeenoyl-acyl carrier protein reductase, (essential for thebiosynthesis offatty acids) inS. pneumoniae.[51]
Resistant pneumococcal strains are called penicillin-resistant pneumococci (PRP),[52] penicillin-resistantStreptococcus pneumoniae (PRSP),[53]Streptococcus pneumoniae penicillin resistant (SPPR)[54] or drug-resistantStrepotococcus pneumoniae (DRSP). In 2015, in the US, there were an estimated 30,000 cases, and in 30% of them the strains were resistant to one or more antibiotics.[55]
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