View source for Streptococcus pneumoniae

{{italic title}}
{{Taxobox
| color = lightgrey <!-- Please read [[WP:Taxobox_usage#Color]] before making any changes to the taxobox color. -->
| name = ''Streptococcus pneumoniae''
| image = Pneumococcus_CDC_PHIL_ID1003.jpg
| image_width = 240px
| image_caption = ''S. pneumoniae'' in spinal fluid. FA stain (digitally colored).
| domain = [[Bacteria]]
| phylum = [[Firmicutes]]
| classis = [[Cocci]]
| ordo = [[Lactobacillales]]
| familia = [[Streptococcaceae]]
| genus = ''[[Streptococcus]]''
| species = '''''S. pneumoniae'''''
| binomial = ''Streptococcus pneumoniae''
| binomial_authority = (Klein 1884)<br>Chester 1901
}}
{{commons category|Streptococcus pneumoniae}}
'''''Streptococcus pneumoniae''''', or '''pneumococcus''', is a [[Gram-positive]], [[hemolysis (microbiology)|alpha-hemolytic]], [[facultative anaerobe|facultative anaerobic]] member of the [[genus]] ''[[Streptococcus]]''.<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | publisher = McGraw Hill | year = 2004 | isbn = 0-8385-8529-9 }}</ref> A significant human [[pathogenic bacterium]], ''S. pneumoniae'' was recognized as a major cause of [[pneumonia]] in the late 19th century, and is the subject of many [[humoral immunity]] studies.

''S. pneumoniae'' resides asymptomatically in the [[nasopharynx]] of healthy carriers. The respiratory tract, sinuses, and nasal cavity are the parts of host body that are usually infected. However, in susceptible individuals, such as elderly and [[immunocompromised]] people and children, the bacterium may become [[pathogen]]ic, spread to other locations and cause disease.  ''S. pneumoniae'' is the main cause of [[community acquired pneumonia]] and [[meningitis]] in children and the elderly, and of [[septicemia]] in [[HIV]]-infected persons. The methods of transmission include sneezing, coughing, and direct contact with an infected person. 

Despite the name, the organism causes many types of [[pneumococcal infection]]s other than [[pneumonia]].  These invasive pneumococcal diseases include [[bronchitis]], [[rhinitis]], [[acute sinusitis]], [[otitis media]], [[conjunctivitis]], [[meningitis]], [[bacteremia]], [[sepsis]], [[osteomyelitis]], [[septic arthritis]], [[endocarditis]], [[peritonitis]], [[pericarditis]], [[cellulitis]], and [[brain abscess]].<ref name="Siemieniuk 2011">{{cite journal|last=Siemieniuk|first=Reed A.C.|coauthors= Gregson, Dan B.; Gill, M. John |title=The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study|journal=BMC Infectious Diseases|date=Nov 2011|volume=11|doi=10.1186/1471-2334-11-314|pmid=22078162|url=http://www.biomedcentral.com/1471-2334/11/314|pmc=3226630|pages=314}}</ref>

''S. pneumoniae'' is one of the most common causes of bacterial meningitis in adults and young adults, along with ''[[Neisseria meningitidis]]'', and is the leading cause of bacterial meningitis in adults in the USA. It is also one of the top two isolates found in ear infection, otitis media.<ref>{{cite journal |author=Dagan R |title=Treatment of acute otitis media—challenges in the era of antibiotic resistance |journal=Vaccine |volume=19 |issue=Suppl 1 |pages=S9–S16 |year= 2000|pmid=11163457 |doi=10.1016/S0264-410X(00)00272-3}}</ref> ''Pneumococcal'' pneumonia is more common in the very young and the very old.
It also is a major bacterium for invasive diseases like pneumonia and meningitis in South Asian children 12 years of age, though the evidence is of low quality and scarce.<ref>{{cite journal|last1=Jaiswal|first1=Nishant|last2=Singh|first2=Meenu|last3=Thumburu|first3=Kiran Kumar|last4=Bharti|first4=Bhavneet|last5=Agarwal|first5=Amit|last6=Kumar|first6=Ajay|last7=Kaur|first7=Harpreet|last8=Chadha|first8=Neelima|last9=Bhutta|first9=Zulfiqar A.|title=Burden of Invasive Pneumococcal Disease in Children Aged 1 Month to 12 Years Living in South Asia: A Systematic Review|journal=PLoS ONE|date=5 May 2014|volume=9|issue=5|pages=e96282|doi=10.1371/journal.pone.0096282| displayauthors = 8}}</ref>

''S. pneumoniae'' can be differentiated from ''[[Streptococcus viridans]]'', some of which are also [[hemolysis (microbiology)|alpha-hemolytic]], using an [[optochin]] test, as ''S. pneumoniae'' is optochin-sensitive. ''S. pneumoniae'' can also be distinguished based on its sensitivity to [[lysis]] by [[bile]], the so-called "bile solubility test". The [[bacterial capsule|encapsulated]], Gram-positive [[coccus|coccoid]] bacteria have a distinctive morphology on Gram stain, [[scalpel|lancet]]-shaped diplococci. They have a [[polysaccharide]] capsule that acts as a [[virulence factor]] for the organism; more than 90 different [[serotype]]s are known, and these types differ in [[virulence]], [[prevalence]], and extent of [[drug resistance]].

==History==
In 1881, the organism, known later in 1886 as the pneumococcus<ref name=Plotkin2012/> for its role as an [etiologic agent] of pneumonia, was first isolated simultaneously and independently by the U.S. Army [[physician]] [[George Miller Sternberg|George Sternberg]]<ref name = Sternberg>{{Cite journal | last = Sternberg | first = George Miller | author-link = George Miller Sternberg | publication-date = 30 April 1881 | title = A fatal form of septicaemia in the rabbit produced by the subcutaneous injection of human saliva. An experimental research | journal = Bulletin of the National Board of Health | publication-place = Baltimore, Maryland | postscript = <!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}} }}.</ref> and the French chemist [[Louis Pasteur]].<ref name = Pasteur>{{Cite journal | last = Pasteur | first = Louis | author-link = Louis Pasteur | publication-date = 1881 | title = Sur une maladie nouvelle provoquée par la salive d'un enfant mort de rage | journal =  Acad. D. Sc. De Paris | volume = 92 | page = 159 | publication-place = Paris, France | postscript = <!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}} }}.</ref>

The organism was termed ''Diplococcus pneumoniae'' from 1920<ref>{{cite journal |author=Winslow, C., and J. Broadhurst |year=1920 |title=The Families and Genera of the Bacteria: Final Report of the Committee of the Society of American Bacteriologists on Characterization and Classification of Bacterial Types |journal=J Bacteriol |volume=5 |issue=3 |pages=191–229 |pmid=16558872 |pmc=378870}}</ref> because of its characteristic appearance in [[Gram stain|Gram-stained]] [[sputum]]. It was renamed ''Streptococcus pneumoniae'' in 1974 because it was very similar to [[Streptococcus|streptococci]].<ref name=Plotkin2012>{{cite book |last1=Plotkin |first1=SA |author-link1=Stanley Plotkin|last2=Orenstein |first2=W |author-link2=Walter Orenstein |last3=Offit |first3=PA |author-link3=Paul Offit |date=September 22,  2012 |title=Vaccines |url=https://books.google.com/books?id=TRyXTLXNA2YC |publisher=Elsevier – Saunders |page=[https://books.google.com/books?id=TRyXTLXNA2YC&pg=PA542&lpg=PA542&dq=%22Streptococcus%20Pneumoniae%20in%201974%22 542] |isbn=978-1455700905 |access-date=July 2, 2015 }}</ref><ref name=Wainer2014>{{cite book |last=Wainer |first=Howard |author-link=Howard Wainer |name-list-format=vanc |year=2014 |title=Medical Illuminations: Using Evidence, Visualization and Statistical Thinking to Improve Healthcare |url=https://books.google.com/books?id=23tpAgAAQBAJ |location= |publisher=Oxford University Press |page=[https://books.google.com/books?id=23tpAgAAQBAJ&pg=PA53&lpg=PA53&dq=%22Looking%20at%20this%20display%22 53] |isbn=978-0199668793 |access-date=July 4, 2015 }} </ref>

''S. pneumoniae'' played a central role in demonstrating genetic material consists of [[DNA]].  In 1928, [[Frederick Griffith]] demonstrated [[transformation (genetics)|transformation]] of life, turning harmless pneumococcus into a lethal form by co-[[inoculating]] the live pneumococci into a mouse along with heat-killed, [[virulent]] pneumococci.<ref name=Griffith1928>{{cite journal |last=Griffith |first=Fred |author-link=Frederick Griffith |date=January 1928 |title=The Significance of Pneumococcal Types |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2167760/pdf/jhyg00267-0003.pdf |journal=Journal of Hygiene |publisher=Cambridge University Press |volume=27 |issue=2 |pages=113–159 |doi=10.1017/S0022172400031879 |pmc=2167760 | name-list-format=vanc |access-date=July 3, 2015 }}</ref>  In 1944, [[Oswald Avery]], [[Colin Munro MacLeod|Colin MacLeod]], and [[Maclyn McCarty]] demonstrated the transforming factor in [[Griffith's experiment]] was DNA, not [[protein]], as was widely believed at the time.<ref>{{cite journal |author=Avery OT, MacLeod CM, and McCarty M |year=1944 |title=Studies on the chemical nature of the substance inducing transformation of pneumococcal types: induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III |journal=J Exp Med |volume=79 |issue=2 |pages=137–158 |pmc=2135445 |pmid=19871359 |doi=10.1084/jem.79.2.137}}</ref> Avery's work marked the birth of the [[molecular genetics|molecular era of genetics]].<ref>{{cite journal |author=Lederberg J |title=The Transformation of Genetics by DNA: An Anniversary Celebration of Avery, Macleod and Mccarty (1944) |journal=Genetics |volume=136 |issue=2 |pages=423&ndash;6 |year=1994 |pmid=8150273 |pmc=1205797}}</ref>

==Genetics==
The [[genome]] of ''S. pneumoniae'' is a closed, circular DNA structure that contains between 2.0 and 2.1 million [[base pair]]s, depending on the [[strain (biology)|strain]]. It has a core set of 1553 [[gene]]s, plus 154 genes in its [[virulome]], which contribute to virulence, and 176 genes that maintain a noninvasive [[phenotype]]. Genetic information can vary up to 10% between strains.<ref>{{cite journal |title=Pathogenesis, treatment, and prevention of pneumococcal pneumonia |author=van der Poll T, Opal SM |journal=Lancet |year=2009 |volume=374 |issue=9700 |pages=1543–56 |pmid=19880020 |doi=10.1016/S0140-6736(09)61114-4}}</ref>

==Transformation in ''S. pneumoniae''==
Natural bacterial transformation involves the transfer of DNA from one bacterium to another through the surrounding medium.  Transformation is a complex, developmental process requiring [[energy]], dependent on expression of numerous genes. In ''S. pneumoniae'' at least 23 genes are required.  In order for a bacterium to bind, take up and recombine [[exogenous DNA]] into its [[chromosome]] it must enter a special physiological state, called [[natural competence|competence]].

Competence, in ''S. pneumoniae'', is induced by DNA-damaging agents such as [[mitomycin C]], a DNA inter-strand [[crosslinking of DNA|cross-linking agent]], and the [[fluoroquinolone]] [[antibiotic]]s [[norfloxacin]], [[levofloxacin]] and [[moxifloxacin]], [[topoisomerase inhibitor]]s that cause double-strand breaks.<ref>{{cite journal |author=Claverys JP, Prudhomme M, Martin B |title=Induction of competence regulons as a general response to stress in gram-positive bacteria |journal=Annu. Rev. Microbiol. |volume=60 |issue= |pages=451–75 |year=2006 |pmid=16771651 |doi=10.1146/annurev.micro.60.080805.142139 |url=}}</ref> Transformation protects ''S. pneumoniae'' against the bactericidal effect of mitomycin C.<ref>{{cite journal |author=Engelmoer DJ, Rozen DE |title=Competence increases survival during stress in Streptococcus pneumoniae |journal=Evolution |volume=65 |issue=12 |pages=3475–85 |date=December 2011 |pmid=22133219 |doi=10.1111/j.1558-5646.2011.01402.x |url=}}</ref>  Michod et al.<ref>{{cite journal |author=Michod RE, Bernstein H, Nedelcu AM |title=Adaptive value of sex in microbial pathogens |journal=Infect. Genet. Evol. |volume=8 |issue=3 |pages=267–85 |date=May 2008 |pmid=18295550 |doi=10.1016/j.meegid.2008.01.002 |url=}}http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf</ref> summarized evidence that induction of competence in ''S. pneumoniae'' is associated with increased resistance to [[oxidative stress]] and increased expression of the RecA protein, a key component of the [[recombinational repair]] machinery for removing [[DNA damage]]s.  On the basis of these findings, they suggested that transformation is an adaptation for repairing oxidative DNA damages.  ''S. pneumoniae'' infection stimulates [[granulocyte|polymorphonuclear leukocytes]] (granulocyte) to produce an oxidative burst that is potentially lethal to the bacteria.  The ability of ''S. pneumoniae'' to repair the oxidative DNA damages in its genome, caused by this host defense, likely contributes to this pathogen’s virulence.

==Infection==
{{Main|Pneumococcal infection}}

''S. pneumoniae'' is part of the normal [[upper respiratory tract]] [[human microbiome|flora]], but, as with many natural flora, it can become pathogenic under the right conditions, like if the immune system of the host is [[immunosuppression|suppressed]]. Invasins, such as [[pneumolysin]], an anti-[[phagocytic]] [[bacterial capsule|capsule]], various [[bacterial adhesin|adhesins]] and [[immunogenic]] [[bacterial cell structure|cell wall components]] are all major [[virulence factors]].

== Vaccine ==
{{Main|Pneumococcal vaccine}}

==Interaction with ''Haemophilus influenzae''==
Both ''[[Haemophilus influenzae]]'' (''H. influenzae'') and ''S. pneumoniae'' can be found in the human [[upper respiratory tract|upper respiratory system]].  A study of competition ''[[in vitro]]'' revealed  ''S. pneumoniae'' overpowered ''H. influenzae'' by attacking it with  [[hydrogen peroxide]].<ref>{{cite journal |author=Pericone, Christopher D., Overweg, Karin, Hermans, Peter W. M., Weiser, Jeffrey N. |title=Inhibitory and Bactericidal Effects of Hydrogen Peroxide Production by Streptococcus pneumoniae on Other Inhabitants of the Upper Respiratory Tract |journal=Infect Immun |volume=68 |issue=7 |pages=3990&ndash;3997 |year=2000 |pmid=10858213 |doi=10.1128/IAI.68.7.3990-3997.2000 |pmc=101678}}</ref>

When both bacteria are placed together into the [[nasal cavity]] of a [[mouse]], within 2 weeks, only ''H. influenzae'' survives.  When both are placed separately into a nasal cavity, each one survives.  Upon examining the upper respiratory tissue from mice exposed to both bacteria, an extraordinarily large number of [[neutrophil]] immune cells were found.  In mice exposed to only one bacterium, the cells were not present.

Lab tests show neutrophils that were exposed to already-dead ''H. influenzae'' were more aggressive in attacking ''S. pneumoniae'' than unexposed neutrophils.  Exposure to killed ''H. influenzae'' had no effect on live ''H. influenzae''.

Two scenarios may be responsible for this response:

# When ''H. influenzae'' is attacked by ''S. pneumoniae'', it signals the [[immune system]] to attack the ''S. pneumoniae''
# The combination of the two [[species]] sets off an immune system alarm that is not set off by either species individually.

It is unclear why ''H. influenzae'' is not affected by the immune system response.<ref name="PLosPathog2006-Lysenko">{{cite journal | author=Lysenko ES, Ratner AJ, Nelson AL, Weiser JN | title=The Role of Innate Immune Responses in the Outcome of Interspecies Competition for Colonization of Mucosal Surfaces | journal=PLoS Pathog | year=2005 | pages=e1 | volume=1 | issue=1 | pmid=16201010 | doi=10.1371/journal.ppat.0010001 | pmc=1238736}} [http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=#10.1371/journal.ppat.0010001 Full text]</ref>

== Diagnosis ==
[[Medical diagnosis|Diagnosis]] is generally made based on clinical suspicion along with a positive culture from a sample from virtually any place in the body. An ASO Titre of >200 units is significant.<ref name="Siemieniuk 2011">{{cite journal|last=Siemieniuk|first=Reed A.C.|coauthors= Gregson, Dan B.; Gill, M. John |title=The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study|journal=BMC Infectious Diseases|date=Nov 2011|volume=11|doi=10.1186/1471-2334-11-314|pmid=22078162|url=http://www.biomedcentral.com/content/pdf/1471-2334-11-314.pdf|pages=314|pmc=3226630}}</ref>  ''S. pneumoniae'' is, in general, [[optochin]] sensitive, although optochin resistance has been observed.<ref>{{Cite journal |title=Optochin resistance in ''Streptococcus pneumoniae'': mechanism, significance, and clinical implications |journal=Journal of Infectious Diseases |url=http://www.journals.uchicago.edu/doi/pdf/10.1086/322803?cookieSet=1 |volume=184 |issue=5 |pages=582–590 |year=2001 |pmid=11474432 |doi=10.1086/322803 |author8=Pikis A, Campos JM, Rodriguez WJ, Keith JM |last1=Pikis |first1=A |last2=Campos |first2=JM |last3=Rodriguez |first3=WJ |last4=Keith |first4=JM}}</ref>

[[Atromentin]] and [[leucomelone]] possess antibacterial activity, inhibiting the [[enzyme]] [[enoyl-acyl carrier protein reductase]], (essential for the [[fatty acid metabolism#Synthesis|biosynthesis]] of [[fatty acid]]s) in ''S. pneumoniae''.<ref name=Zheng2006>{{cite journal |author=Zheng CJ, Sohn MJ, Kim WG. |year=2006 |title=Atromentin and [[leucomelone]], the first inhibitors specific to enoyl-ACP reductase (FabK) of ''Streptococcus pneumoniae'' |journal=Journal of Antibiotics |volume=59 |issue=12 |pages=808–12 |doi=10.1038/ja.2006.108 |pmid=17323650}}</ref>

==See also==
* [[Natural competence]]
* [[Transformation (genetics)]]
* [[Pneumococcal Awareness Council of Experts]]

==References==
{{Reflist|2}}

==External links==

{{TaxonIds |eol=974503 |ncbi=1313}}
* [http://www.gavialliance.org GAVI Alliance]
* [http://www.preventpneumo.org PneumoADIP]
* [http://www.path.org/vaccineresources/pneumococcus.php PATH's Vaccine Resource Library pneumococcal resources]
* {{cite book |author=Centers for Disease Control and Prevention |chapter=Ch. 16: Pneumococcal Disease |chapterurl=http://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html |editor=Atkinson W, Wolfe S, Hamborsky J |title=Epidemiology and Prevention of Vaccine-Preventable Diseases |publisher=Public Health Foundation |location=Washington DC |year=2012 |edition=12th |url=http://www.cdc.gov/vaccines/pubs/pinkbook/table-of-contents.html |pages=233–248}}

{{Gram-positive bacterial diseases}}

[[Category:Streptococcaceae]]
[[Category:Polysaccharide encapsulated bacteria]]
[[Category:Pneumonia]]
[[Category:Gram-positive bacteria]]
[[Category:Pathogenic bacteria]]
[[Category:Bacteria with sequenced genomes]]