View source for Integron

'''Integrons''' are genetic mechanisms that allow bacteria to adapt and evolve rapidly through the stockpiling and expression of new genes.<ref>{{Cite journal|title=ASMscience {{!}} The Integron: Adaptation On Demand|url=http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.MDNA3-0019-2014|doi=10.1128/microbiolspec.mdna3-0019-2014 | volume=3|year=2015|journal=Microbiology Spectrum | last1 = Antonio Escudero | first1 = José | last2 = Mazel | first2 = Didier | last3 = Nivina | first3 = Aleksandra | last4 = Loot | first4 = Céline|issue=2|pages=MDNA3–0019–2014|pmid=26104695| url-access=subscription }}</ref> These genes are embedded in a specific genetic structure called [[gene cassette]] (a term that is lately changing to integron cassette) that generally carries one promoterless [[open reading frame]] (ORF) together with a recombination site (''attC''). Integron cassettes are incorporated to the ''attI'' site of the integron platform by [[site-specific recombination]] reactions mediated by the integrase.

== Discovery ==
Integrons were initially discovered on conjugative plasmids through their role in antibiotic resistance.<ref>{{cite journal | last1 = Mazel | year = 2006 | title = Integrons: agents of bacterial evolution | journal = Nature Reviews Microbiology | volume = 4 | issue = 8| pages = 608–620 | doi = 10.1038/nrmicro1462 | pmid = 16845431 | s2cid = 4407151 }}</ref> Indeed, these mobile integrons, as they are now known, can carry a variety of cassettes containing genes that are almost exclusively related to antibiotic resistance. Further studies have come to the conclusion that integrons are chromosomal elements, and that their mobilisation onto plasmids has been fostered by transposons and selected by the intensive use of antibiotics. The function of the majority of cassettes found in chromosomal integrons remains unknown.

== Integron function ==
Cassette maintenance requires that they be integrated within a replicative element (chromosome, plasmids). The integrase encoded by the integron preferentially catalyses two types of recombination reaction: 1) attC x attC, which results in cassette excision, 2) attI x attC, which allows integration of the cassette at the attI site of the integron. Once inserted, the cassette is maintained during cell division.<ref name=":0">{{Cite journal |last1=Hall |first1=Ruth M. |last2=Collis |first2=Christina M. |date=2006-10-27 |title=Mobile gene cassettes and integrons: capture and spread of genes by site-specific recombination |journal=Molecular Microbiology |volume=15 |issue=4 |pages=593–600 |doi=10.1111/j.1365-2958.1995.tb02368.x |pmid=7783631 |s2cid=16476838 |issn=0950-382X|doi-access=free }}</ref> Successive integrations of gene cassettes result in the formation of a series of cassettes. The cassette integrated last is then the one closest to the Pc promoter at the attI site. The IntI-catalysed mode of recombination involves structured single-stranded DNA and gives the attC site recognition mode unique characteristics.<ref>{{Cite journal |last1=MacDonald |first1=Douglas |last2=Demarre |first2=Gaëlle |last3=Bouvier |first3=Marie |last4=Mazel |first4=Didier |last5=Gopaul |first5=Deshmukh N. |date=2006 |title=Structural basis for broad DNA-specificity in integron recombination |journal=Nature |volume=440 |issue=7088 |pages=1157–1162 |doi=10.1038/nature04643 |pmid=16641988 |bibcode=2006Natur.440.1157M |s2cid=4403903 |issn=0028-0836}}</ref> The integration of gene cassettes within an integron also provides a Pc promoter that allows expression of all cassettes in the array, much like an [[operon]].<ref name=":0" /> The level of [[gene expression]] of a cassette is then a function of the number and nature of the cassettes that precede it. In 2009, [[:fr:Didier Mazel|Didier Mazel]] and his team showed that the expression of the IntI integrase was controlled by the bacterial [[SOS response]], thus coupling this adaptive apparatus to the stress response in bacteria.<ref>{{Cite journal |last1=Guerin |first1=Émilie |last2=Cambray |first2=Guillaume |last3=Sanchez-Alberola |first3=Neus |last4=Campoy |first4=Susana |last5=Erill |first5=Ivan |last6=Da Re |first6=Sandra |last7=Gonzalez-Zorn |first7=Bruno |last8=Barbé |first8=Jordi |last9=Ploy |first9=Marie-Cécile |last10=Mazel |first10=Didier |date=2009-05-22 |title=The SOS Response Controls Integron Recombination |url=https://www.science.org/doi/10.1126/science.1172914 |journal=Science |language=en |volume=324 |issue=5930 |page=1034 |doi=10.1126/science.1172914 |pmid=19460999 |bibcode=2009Sci...324.1034G |s2cid=42334786 |issn=0036-8075}}</ref> In 2025 two groups found that many cassettes encode bacterial anti-phage proteins—these are carried both on mobile integrons <ref>{{Cite journal |last1=Kieffer |first1=Nicolas |last2=Hipólito |first2=Alberto |last3=Ortiz-Miravalles |first3=Laura |last4=Blanco |first4=Paula |last5=Delobelle |first5=Thomas |last6=Vizuete |first6=Patricia |last7=Ojeda |first7=Francisco Manuel |last8=Jové |first8=Thomas |last9=Jurenas |first9=Dukas |last10=García-Quintanilla |first10=Meritxell |last11=Carvalho |first11=André |last12=Domingo-Calap |first12=Pilar |last13=Escudero |first13=José Antonio |date=2025-05-08 |title=Mobile integrons encode phage defense systems |url=https://www.science.org/doi/10.1126/science.ads0915 |journal=Science |language=en |volume=388 |issue=6747 |article-number=eads0915 |doi=10.1126/science.ads0915 |pmid=40338999 |bibcode=2025Sci...388S0915K |issn=0036-8075|hdl=10261/392908 |hdl-access=free }}</ref> and sedentary chromosomal integrons.<ref>{{Cite journal |last1=Darracq |first1=Baptiste |last2=Littner |first2=Eloi |last3=Brunie |first3=Manon |last4=Bos |first4=Julia |last5=Kaminski |first5=Pierre Alexandre |last6=Depardieu |first6=Florence |last7=Slesak |first7=Weronika |last8=Debatisse |first8=Kevin |last9=Touchon |first9=Marie |last10=Bernheim |first10=Aude |last11=Bikard |first11=David |last12=Le Roux |first12=Frédérique |last13=Mazel |first13=Didier |last14=Rocha |first14=Eduardo P. C. |last15=Loot |first15=Céline |date=2025-05-08 |title=Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems |journal=Science |language=en |volume=388 |issue=6747 |article-number=eads0768 |doi=10.1126/science.ads0768 |issn=0036-8075|doi-access=free |pmid=40339013 |bibcode=2025Sci...388S0768D }}</ref>

== Structure ==
An integron is minimally composed of:<ref>{{cite journal|doi=10.1023/A:1015361704475|year=2002|last1=Kovalevskaya|first1=N. P.|journal=Molecular Biology|volume=36|issue=2|pages=196–201|title=Mobile Gene Cassettes and Integrons|s2cid=2078235}}</ref><ref>Hall R, Collis C, Kim M, Partridge S, Recchia G, Stokes H (1999) ''Mobile gene cassettes and integrons in evolution''.</ref>
* a gene encoding for a site-specific [[recombinase]]: ''intI, ''belonging to the [[integrase]] family
* a proximal [[Genetic recombination|recombination]] site: ''attI'', which is recognized by the integrase<ref>{{cite journal|pmid=7783631|year=1995|last1=Hall|first1=RM|last2=Collis|first2=CM|title=Mobile gene cassettes and integrons: Capture and spread of genes by site-specific recombination|volume=15|issue=4|pages=593–600|journal=Molecular Microbiology|doi=10.1111/j.1365-2958.1995.tb02368.x |doi-access=free}}</ref> and at which gene cassettes may be inserted
* a promoter: ''Pc'', which directs transcription of cassette-encoded genes

=== Gene cassettes ===
{{Main|Gene cassette|l1=Gene cassette}}
Additionally, an integron will usually contain one or more gene cassettes that have been incorporated into it. The gene cassettes may encode genes for [[antibiotic resistance]],<ref>{{Cite journal |last1=Hipólito |first1=Alberto|last2=García-Pastor |first2=Lucía |last3=Vergara |first3=Ester |last4=Jové |first4=Thomas |last5=Escudero|first5=José Antonio |date=2023 |title=Profile and resistance levels of 136 integron resistance genes |journal=npj Antimicrobials and Resistance |volume=1 |issue=1 |page=13 |doi=10.1038/s44259-023-00014-3|doi-access=free |pmid=39843947 |pmc=11721406 }}</ref> although most genes in integrons are uncharacterized. An ''attC'' sequence (also called 59-be) is a repeat that flanks cassettes and enables cassettes to be integrated at the ''attI'' site, excised and undergo [[horizontal gene transfer]].

== Occurrence ==
Integrons may be found as part of [[mobile genetic elements]] such as [[plasmids]] and [[transposon]]s. Integrons can also be found in [[chromosomes]].

== Terminology ==
The term ''super-integron'' was first applied in 1998 (but without definition) to the integron with a long cassette array on the small chromosome of ''[[Vibrio cholerae]]''.<ref name="Hall2004">{{cite journal|doi=10.1099/mic.0.26854-0|title=Integrons or super integrons?|year=2004|last1=Hall|first1=R. M.|journal=Microbiology|volume=150|pages=3–4|pmid=14702391|last2=Stokes|first2=HW|issue=Pt 1|doi-access=free}}</ref><ref>{{cite journal|doi=10.1126/science.280.5363.605|title=A Distinctive Class of Integron in the Vibrio cholerae Genome|year=1998|last1=Mazel|first1=D.|journal=Science|volume=280|issue=5363|pages=605–8|pmid=9554855|last2=Dychinco|first2=B|last3=Webb|first3=VA|last4=Davies|first4=J|bibcode=1998Sci...280..605M}}</ref> The term has since been used for integrons of various cassette array lengths or for integrons on bacterial chromosomes (versus, for example, plasmids).  Use of "super-integron" is now discouraged since its meaning is unclear.<ref name="Hall2004" />

In more modern usage, an integron located on a bacterial chromosome is termed a ''sedentary chromosomal integron'', and one associated with transposons or plasmids is called a ''mobile integron''.<ref>{{cite journal |last1=Loot |first1=Céline |last2=Nivina |first2=Aleksandra |last3=Cury |first3=Jean |last4=Escudero |first4=José Antonio |last5=Ducos-Galand |first5=Magaly |last6=Bikard |first6=David |last7=Rocha |first7=Eduardo P. C. |last8=Mazel |first8=Didier |title=Differences in Integron Cassette Excision Dynamics Shape a Trade-Off between Evolvability and Genetic Capacitance |journal=mBio |date=3 May 2017 |volume=8 |issue=2 |doi=10.1128/mBio.02296-16|pmid=28351923 |pmc=5371416 }}</ref>

==References==
{{reflist|2}}
*[http://www.medterms.com/script/main/art.asp?articlekey=32273 Medical terms] {{Webarchive|url=https://web.archive.org/web/20120807045945/http://www.medterms.com/script/main/art.asp?articlekey=32273 |date=2012-08-07 }}

==Further reading==
* {{cite journal | year = 2002 | title = Characterization of the Class 3 Integron and the Site-Specific Recombination System It Determines | url= | journal = Journal of Bacteriology | volume = 184 | issue = 11| pages = 3017–3026 | doi=10.1128/jb.184.11.3017-3026.2002| pmc = 135066 | pmid=12003943 | last1 = Collis | first1 = CM | last2 = Kim | first2 = MJ | last3 = Partridge | first3 = SR | last4 = Stokes | first4 = HW | last5 = Hall | first5 = RM}}
*{{cite journal | pmid = 9835490 | volume=42 | title=Class 1 integron-borne multiple-antibiotic resistance carried by IncFI and IncL/M plasmids in Salmonella enterica serotype typhimurium | pmc=105998 | year=1998 | journal=Antimicrob Agents Chemother | pages=3053–8 | last1 = Tosini | first1 = F | last2 = Visca | first2 = P | last3 = Luzzi | first3 = I | last4 = Dionisi | first4 = AM | last5 = Pezzella | first5 = C | last6 = Petrucca | first6 = A | last7 = Carattoli | first7 = A | issue=12 | doi=10.1128/aac.42.12.3053}}
* {{cite journal | last1 = Mazel | first1 = D | year = 2006| title = Integrons: agents of bacterial evolution | journal = Nature Reviews Microbiology | volume = 4 | issue = 8| pages = 608–620 | doi = 10.1038/nrmicro1462 | pmid = 16845431 | s2cid = 4407151 }}

==External links==
*[https://github.com/gem-pasteur/Integron_Finder/ IntegronFinder] - A tool to detect integrons in bacterial genomes
*[http://integrall.bio.ua.pt/ INTEGRALL] - The Integron Database

[[Category:Genetics]]
[[Category:Bacteriology]]
[[Category:Enzymes]]