Mobile Integrons Encode Phage Defence Systems

Nicolas Kieffer*, Alberto Hipólito*, Laura Ortiz-Miravalles, Paula BlancoThomas Delobelle, Francisco Manuel Ojeda, Thomas Jové, Dukas Jurenas, Meritxell García-Quintanilla, Pilar Domingo-Calap, José Antonio Escudero


Laura Ortiz, Amalia Prieto, Nicolas Kieffer, Ester Vergara, Rafael Canton, Alvaro San Millan, Fernando Baquero, Alberto Hipólito, Jose Antonio Escudero

The Expression of Integron Arrays is Shaped by the Translation Rate of Cassettes

André Carvalho, Alberto Hipólito,Filipa Trigo da Roza, Lucía García-Pastor, Ester Vergara, Aránzazu Buendía, Teresa García-Seco, José Antonio Escudero

Nature communications


Chromosomal Integrons are Genetically and Functionally Isolated Units of Genomes

Paula Blanco, Filipa Trigo da Roza, Laura Toribio-Celestino, Lucía García-Pastor, Niccolò Caselli, Álvaro Morón, Francisco Ojeda, Baptiste Darracq, Ester Vergara, Francisco Amaro, Álvaro San Millán, Ole Skovgaard, Didier Mazel, Céline Loot, José Antonio Escudero

bioRxiv 2023.11.17.567518; doi:

Under review in Nucleic Acids Research
Paula Blanco, Alberto Hipólito, Lucía García-Pastor, Filipa Trigo da Roza, Laura Toribio-Celestino, Alba Cristina Ortega, Ester Vergara, Álvaro San Millán, José Antonio Escudero
Nucleic Acids Research. (2024) gkad1252,
bioRxiv 2023.11.21.568050; doi:
A rugged yet easily navigable fitness landscape of antibiotic resistance
Papkou A, Garcia-Pastor L,  Escudero JA, Wagner A.
Hipólito A, García-Pastor L, Vergara E, Jové T, Escudero JA 
npj Antimicrob Resist 1, 13 (2023).


The expression of aminoglycoside resistance genes in integron cassettes is not controlled by riboswitches.
Hipólito A, García-Pastor L, Blanco P, Trigo da Roza F, Kieffer N, Vergara E, Jové T, Álvarez J, Escudero JA.
Nucleic Acids Res. 2022 Aug 26;50(15):8566-8579. doi: 10.1093/nar/gkac662.PMID: 35947699


Genomic characterization of multidrug-resistant Salmonella serovar Kentucky ST198 isolated in poultry flocks in Spain (2011-2017).

Samper-Cativiela C, Diéguez-Roda B, Trigo da Roza F, Ugarte-Ruiz M, Elnekave E, Lim S, Hernández M, Abad D, Collado S, Sáez JL, de Frutos C, Agüero M, Moreno MÁ, Escudero JA, Álvarez J.

Microb Genom. 2022 Mar;8(3). doi: 10.1099/mgen.0.000773.


Integron activity accelerates the evolution of antibiotic resistance.

Souque C, Escudero JA, MacLean RC.

Elife. 2021 Feb 26;10:e62474. doi: 10.7554/eLife.62474.


Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions.

Escudero JA, Nivina A, Kemble HE, Loot C, Tenaillon O, Mazel D.
Elife. 2020 Dec 15;9:e58061. doi: 10.7554/eLife.58061.
Vit C, Loot C, Escudero JA, Nivina A, Mazel D.
Methods Mol Biol. 2020;2075:189-208. doi: 10.1007/978-1-4939-9877-7_14.

Recoding of synonymous genes to expand evolutionary landscapes requires control of secondary structure affecting translation.

Escudero JA, Nivina A, Cambray G, López-Igual R, Loot C, Mazel D.

Biotechnol Bioeng. 2018 Jan;115(1):184-191. doi: 10.1002/bit.26450. Epub 2017 Oct 16.


Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance.

Escudero JA, MacLean RC, San Millan A.
J Vis Exp. 2018 May 2;(135):57386. doi: 10.3791/57386.
Rodriguez-Beltran J, Hernandez-Beltran JCR, DelaFuente J, Escudero JA, Fuentes-Hernandez A, MacLean RC, Peña-Miller R, San Millan A.
Nat Ecol Evol. 2018 May;2(5):873-881. doi: 10.1038/s41559-018-0529-z. Epub 2018 Apr 9.

Highly Tigecycline-Resistant Klebsiella pneumoniae Sequence Type 11 (ST11) and ST147 Isolates from Companion Animals.

Ovejero CM, Escudero JA, Thomas-Lopez D, Hoefer A, Moyano G, Montero N, Martin-Espada C, Gonzalez-Zorn B.

Antimicrob Agents Chemother. 2017 May 24;61(6). pii: e02640-16. doi: 10.1128/AAC.02640-16. Print 2017 Jun.


Differences in Integron Cassette Excision Dynamics Shape a Trade-Off between Evolvability and Genetic Capacitance.

Loot C, Nivina A, Cury J, Escudero JA, Ducos-Galand M, Bikard D, Rocha EP, Mazel D.

MBio. 2017 Mar 28;8(2). pii: e02296-16. doi: 10.1128/mBio.02296-16.


Multicopy plasmids potentiate the evolution of antibiotic resistance in bacteria.

San Millan A, Escudero JA, Gifford DR, Mazel D, MacLean RC.

Nat Ecol Evol. 2016 Nov 7;1(1):10. doi: 10.1038/s41559-016-0010.


Efficiency of integron cassette insertion in correct orientation is ensured by the interplay of the three unpaired features of attC recombination sites.

Nivina A, Escudero JA, Vit C, Mazel D, Loot C.

Nucleic Acids Res. 2016 Sep 19;44(16):7792-803. doi: 10.1093/nar/gkw646. Epub 2016 Aug 5.


Unmasking the ancestral activity of integron integrases reveals a smooth evolutionary transition during functional innovation.

Escudero JA, Loot C, Parissi V, Nivina A, Bouchier C, Mazel D.

Nat Commun. 2016 Mar 10;7:10937. doi: 10.1038/ncomms10937.


Sequencing of plasmids pAMBL1 and pAMBL2 from Pseudomonas aeruginosa reveals a blaVIM-1 amplification causing high-level carbapenem resistance.

San Millan A, Toll-Riera M, Escudero JA, Cantón R, Coque TM, MacLean RC.

J Antimicrob Chemother. 2015 Nov;70(11):3000-3. doi: 10.1093/jac/dkv222. Epub 2015 Jul 24.


The Integron: Adaptation On Demand.

Escudero JA, Loot C, Nivina A, Mazel D.

Microbiol Spectr. 2015 Apr;3(2):MDNA3-0019-2014. doi: 10.1128/microbiolspec.MDNA3-0019-2014. Review.


Culturable aerobic and facultative bacteria from the gut of the polyphagic dung beetle Thorectes lusitanicus.

Hernández N, Escudero JA, San Millán Á, González-Zorn B, Lobo JM, Verdú JR, Suárez M.

Insect Sci. 2015 Apr;22(2):178-90. doi: 10.1111/1744-7917.12094. Epub 2014 Apr 30.


The integron integrase efficiently prevents the melting effect of Escherichia coli single-stranded DNA-binding protein on folded attC sites.

Loot C, Parissi V, Escudero JA, Amarir-Bouhram J, Bikard D, Mazel D.

J Bacteriol. 2014 Feb;196(4):762-71. doi: 10.1128/JB.01109-13. Epub 2013 Dec 2.


First identification of Salmonella Urbana and Salmonella Ouakam in humans in Africa.

Saba CK, Escudero JA, Herrera-Leon S, Porrero MC, Suarez M, Dominguez L, Demuyakor B, Gonzalez-Zorn B.

J Infect Dev Ctries. 2013 Oct 15;7(10):691-5. doi: 10.3855/jidc.3548.


Ecology of antimicrobial resistance: humans, animals, food and environment.

González-Zorn B, Escudero JA.

Int Microbiol. 2012 Sep;15(3):101-9. Review.


SatR is a repressor of fluoroquinolone efflux pump SatAB.

Escudero JA, San Millan A, Montero N, Gutierrez B, Ovejero CM, Carrilero L, González-Zorn B.

Antimicrob Agents Chemother. 2013 Jul;57(7):3430-3. doi: 10.1128/AAC.00515-13. Epub 2013 May 6.


Replicative resolution of integron cassette insertion.

Loot C, Ducos-Galand M, Escudero JA, Bouvier M, Mazel D.

Nucleic Acids Res. 2012 Sep 1;40(17):8361-70. Epub 2012 Jun 26.


Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases.

Gutierrez B, Escudero JA, San Millan A, Hidalgo L, Carrilero L, Ovejero CM, Santos-Lopez A, Thomas-Lopez D, Gonzalez-Zorn B.

Antimicrob Agents Chemother. 2012 May;56(5):2335-41. doi: 10.1128/AAC.06066-11. Epub 2012 Feb 13.


Fluoroquinolone efflux in Streptococcus suis is mediated by SatAB and not by SmrA.

Escudero JA, San Millan A, Gutierrez B, Hidalgo L, La Ragione RM, AbuOun M, Galimand M, Ferrándiz MJ, Domínguez L, de la Campa AG, Gonzalez-Zorn B.

Antimicrob Agents Chemother. 2011 Dec;55(12):5850-60. doi: 10.1128/AAC.00498-11. Epub 2011 Sep 19.


ArmA methyltransferase in a monophasic Salmonella enterica isolate from food.

Granier SA, Hidalgo L, San Millan A, Escudero JA, Gutierrez B, Brisabois A, Gonzalez-Zorn B.

Antimicrob Agents Chemother. 2011 Nov;55(11):5262-6. doi: 10.1128/AAC.00308-11. Epub 2011 Aug 22.


Contribution of ROB-1 and PBP3 mutations to the resistance phenotype of a β-lactamase-positive amoxicillin/clavulanic acid-resistant Haemophilus influenzae carrying plasmid pB1000 in Italy.

San Millan A, Giufré M, Escudero JA, Hidalgo L, Gutierrez B, Cerquetti M, Gonzalez-Zorn B.

J Antimicrob Chemother. 2011 Jan;66(1):96-9. doi: 10.1093/jac/dkq392. Epub 2010 Oct 26.


16S rRNA methyltransferase RmtC in Salmonella enterica serovar Virchow.

Hopkins KL, Escudero JA, Hidalgo L, Gonzalez-Zorn B.

Emerg Infect Dis. 2010 Apr;16(4):712-5. doi: 10.3201/eid1604.090736.


Haemophilus influenzae clinical isolates with plasmid pB1000 bearing blaROB-1: fitness cost and interspecies dissemination.

San Millan A, Garcia-Cobos S, Escudero JA, Hidalgo L, Gutierrez B, Carrilero L, Campos J, Gonzalez-Zorn B.

Antimicrob Agents Chemother. 2010 Apr;54(4):1506-11. doi: 10.1128/AAC.01489-09. Epub 2010 Jan 19.