Identification of promoter activity in gene-less cassettes from Vibrionaceae superintegrons.

Integrons are genetic platforms that acquire new genes encoded in integron cassettes (ICs), building arrays of adaptive functions. ICs generally encode promoterless genes, whose expression relies on the platform-associated Pc promoter, with the cassette array functioning as an operon-like structure regulated by the distance to the Pc. This is relevant in large sedentary chromosomal integrons (SCIs) carrying hundreds of ICs, like those in Vibrio species. We selected 29 gene-less cassettes in four Vibrio SCIs, and explored whether their function could be related to the transcription regulation of adjacent ICs. We show that most gene-less cassettes have promoter activity on the sense strand, enhancing the expression of downstream cassettes. Additionally, we identified the transcription start sites of gene-less ICs through 5'-RACE. Accordingly, we found that most of the superintegron in Vibrio cholerae is not silent. These promoter cassettes can trigger the expression of a silent dfrB9 cassette downstream, increasing trimethoprim resistance >512-fold in V. cholerae and Escherichia coli. Furthermore, one cassette with an antisense promoter can reduce trimethoprim resistance when cloned downstream. Our findings highlight the regulatory role of gene-less cassettes in the expression of adjacent cassettes, emphasizing their significance in SCIs and their clinical importance if captured by mobile integrons.

A rugged yet easily navigable fitness landscape.

Fitness landscape theory predicts that rugged landscapes with multiple peaks impair Darwinian evolution, but experimental evidence is limited. In this study, we used genome editing to map the fitness of >260,000 genotypes of the key metabolic enzyme dihydrofolate reductase in the presence of the antibiotic trimethoprim, which targets this enzyme. The resulting landscape is highly rugged and harbors 514 fitness peaks. However, its highest peaks are accessible to evolving populations via abundant fitness-increasing paths. Different peaks share large basins of attraction that render the outcome of adaptive evolution highly contingent on chance events. Our work shows that ruggedness need not be an obstacle to Darwinian evolution but can reduce its predictability. If true in general, the complexity of optimization problems on realistic landscapes may require reappraisal.

Parental Socialization and Adjustment Components in Adolescents and Middle-Aged Adults: How are They Related?

Purpose: Classic studies mainly of European-American families broadly identify the benefits of parental strictness combined with parental warmth. However, current research tends to identify parental warmth as positive for adjustment, even without parental strictness. In addition, less is known about the relationship between parenting and adjustment beyond adolescence. The present study examined warmth and strictness and its relationship with self, sexism, and stimulation values. Self-esteem, academic-professional self-concept, benevolent sexism, and stimulation values were used to capture adjustment. Patients and Methods: Participants (n = 1125) were adolescents and adult children of middle-age from Spain. The statistical analyses used were correlation analysis and multiple linear regression. Results: In general, the relationship between parenting and adjustment was found to have a similar pattern for adolescent and middle-aged adult children, although more marked in adolescents. Parental warmth and strictness were predictors of adjustment, but in a different direction. Specifically, parental warmth positively predicted academic-professional self-concept and self-esteem, whereas parental strictness was detrimental as a predictor of higher benevolent sexism. Conclusion: Overall, the present findings suggest that an effective socialization during the socialization years and even beyond can be positively predicted by parental warmth, whereas parental strictness might be unnecessary or even detrimental.

The expression of aminoglycoside resistance genes in integron cassettes is not controlled by riboswitches.

Regulation of gene expression is a key factor influencing the success of antimicrobial resistance determinants. A variety of determinants conferring resistance against aminoglycosides (Ag) are commonly found in clinically relevant bacteria, but whether their expression is regulated or not is controversial. The expression of several Ag resistance genes has been reported to be controlled by a riboswitch mechanism encoded in a conserved sequence. Yet this sequence corresponds to the integration site of an integron, a genetic platform that recruits genes of different functions, making the presence of such a riboswitch counterintuitive. We provide, for the first time, experimental evidence against the existence of such Ag-sensing riboswitch. We first tried to reproduce the induction of the well characterized aacA5 gene using its native genetic environment, but were unsuccessful. We then broadened our approach and analyzed the inducibility of all AgR genes encoded in integrons against a variety of antibiotics. We could not observe biologically relevant induction rates for any gene in the presence of several aminoglycosides. Instead, unrelated antibiotics produced mild but consistently higher increases in expression, that were the result of pleiotropic effects. Our findings rule out the riboswitch control of aminoglycoside resistance genes in integrons.

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

Salmonella Kentucky is commonly found in poultry and rarely associated with human disease. However, a multidrug-resistant (MDR) S. Kentucky clone [sequence type (ST)198] has been increasingly reported globally in humans and animals. Our aim here was to assess if the recently reported increase of S. Kentucky in poultry in Spain was associated with the ST198 clone and to characterize this MDR clone and its distribution in Spain. Sixty-six isolates retrieved from turkey, laying hen and broiler in 2011-2017 were subjected to whole-genome sequencing to assess their sequence type, genetic relatedness, and presence of antimicrobial resistance genes (ARGs), plasmid replicons and virulence factors. Thirteen strains were further analysed using long-read sequencing technologies to characterize the genetic background associated with ARGs. All isolates belonged to the ST198 clone and were grouped in three clades associated with the presence of a specific point mutation in the gyrA gene, their geographical origin and isolation year. All strains carried between one and 16 ARGs whose presence correlated with the resistance phenotype to between two and eight antimicrobials. The ARGs were located in the Salmonella genomic island (SGI-1) and in some cases (blaSHV-12, catA1, cmlA1, dfrA and multiple aminoglycoside-resistance genes) in IncHI2/IncI1 plasmids, some of which were consistently detected in different years/farms in certain regions, suggesting they could persist over time. Our results indicate that the MDR S. Kentucky ST198 is present in all investigated poultry hosts in Spain, and that certain strains also carry additional plasmid-mediated ARGs, thus increasing its potential public health significance.

Integron activity accelerates the evolution of antibiotic resistance.

Mobile integrons are widespread genetic platforms that allow bacteria to modulate the expression of antibiotic resistance cassettes by shuffling their position from a common promoter. Antibiotic stress induces the expression of an integrase that excises and integrates cassettes, and this unique recombination and expression system is thought to allow bacteria to 'evolve on demand' in response to antibiotic pressure. To test this hypothesis, we inserted a custom three-cassette integron into Pseudomonas aeruginosa and used experimental evolution to measure the impact of integrase activity on adaptation to gentamicin. Crucially, integrase activity accelerated evolution by increasing the expression of a gentamicin resistance cassette through duplications and by eliminating redundant cassettes. Importantly, we found no evidence of deleterious off-target effects of integrase activity. In summary, integrons accelerate resistance evolution by rapidly generating combinatorial variation in cassette composition while maintaining genomic integrity.

From urinary tract infections to bacterial pneumonia, many diseases can now be treated through a course of antibiotics. Yet bacteria have evolved to respond to this threat, gaining new antibiotic resistance genes that allow them to evade the drugs. Addressing this growing issue requires to either discover new antibiotics, or to stop resistance before it emerges ­ a strategy that can only work if scientists know exactly how this mechanism takes place. For bacteria, it is a waste of resources to produce the proteins that confer resistance if antibiotics are absent. In fact, doing so can decrease their chance to survive and reproduce. A genetic element known as an integron can help to manage that burden. This piece of genetic information is formed of a succession of 'cassettes' containing antibiotic resistance genes. More proteins are made from the genes present at the start of the integron, compared to the ones towards the end. When bacteria encounter antibiotics, an enzyme called integrase is activated, allowing the organisms to shuffle the order of their cassettes in the integron. It is thought ­ but not yet proven ­ that this mechanism helps bacteria to activate their resistance 'on demand'. To find out, Souque et al. engineered the bacteria Pseudomonas aeruginosa to carry a custom integron with three cassettes, each helping the organism to resist to a different antibiotic. In addition, only half of the bacteria had a working integrase and could therefore shuffle their gene cassettes. The organisms were then exposed to an increasing amount of the antibiotics for which the cassette in the last position provided resistance. The bacteria with a working integrase survived longer than those without, as they were able to shuffle their cassettes and move the useful antibiotic resistance gene into top position. In addition, the cassettes carrying the genes to resist to other types of antibiotics were excised from the genetic information and lost. Understanding integrons could guide future antibiotic treatment strategies, for instance by combining antibiotics with chemicals that block integrase activity. It might also be possible to force bacteria to delete resistance cassettes by cycling through different antibiotics.

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

Molecular examples of evolutionary innovation are scarce and generally involve point mutations. Innovation can occur through larger rearrangements, but here experimental data is extremely limited. Integron integrases innovated from double-strand- toward single-strand-DNA recombination through the acquisition of the I2 α-helix. To investigate how this transition was possible, we have evolved integrase IntI1 to what should correspond to an early innovation state by selecting for its ancestral activity. Using synonymous alleles to enlarge sequence space exploration, we have retrieved 13 mutations affecting both I2 and the multimerization domains of IntI1. We circumvented epistasis constraints among them using a combinatorial library that revealed their individual and collective fitness effects. We obtained up to 104-fold increases in ancestral activity with various asymmetrical trade-offs in single-strand-DNA recombination. We show that high levels of primary and promiscuous functions could have initially coexisted following I2 acquisition, paving the way for a gradual evolution toward innovation.

Parental Socialization and Its Impact across the Lifespan.

Classical studies have found that parental warmth combined with parental strictness is the best parental strategy to promote children's psychosocial development. Nevertheless, a growing set of emergent studies has questioned the benefits of parental strictness. The present study examined parental socialization and its short- and long-term impact on the psychosocial development of adolescents and adult children. The sample consisted of 2150 Spanish participants, 623 adolescents (12-18 years), 619 young adults (19-35 years), 502 middle-aged adults (35-59 years), and 406 older adults (60 years or older). Families were classified into one of four typologies (indulgent, authoritative, authoritarian, and neglectful). Psychosocial development was examined with five indicators (physical and family self-concept, nervousness, empathy, and internalization of social values of benevolence). The results show a common short- and long-term pattern between parenting styles and psychosocial development: the indulgent style equaled or even surpassed the authoritative style, whereas the neglectful and authoritarian styles were associated with low scores. The present findings were discussed by considering the importance of the cultural context in family socialization. Additionally, the long-term impact of parental socialization seems to be crucial, even in adulthood.

Estilos parentales y su contribución al ajuste personal y social de los hijos / Parenting styles and their contribution to children personal and social adjustment

INTRODUCCIÓN Y OBJETIVOS: Este estudio analiza la relación entre los estilos parentales (indulgente, autorizativo, autoritario y negligente) con el patrón de ajuste personal y social, a corto y largo plazo, en hijos adolescentes y adultos. MATERIAL Y MÉTODOS: La muestra fue de 2,119 hijos españoles (59.2% mujeres), 623 adolescentes (12-18 años), 591 jóvenes adultos (19-35 años), 509 adultos de mediana edad (36-59 años) y 396 adultos mayores (60 años o más). Las familias se clasificaron en una de las cuatro tipologías parentales (indulgente, autorizativa, autoritaria y negligente) según sus puntuaciones en las dos dimensiones principales (aceptación/implicación y severidad/imposición). El ajuste personal y social de los hijos se midió con autoconcepto familiar, autoestima, agresividad, prejuicio sexista e internalización de valores sociales de universalismo. RESULTADOS: Los resultados mostraron un patrón común a corto y largo plazo entre los estilos parentales y el ajuste personal y social. El estilo indulgente se relacionó con iguales o incluso mejores puntuaciones en ajuste personal y social que el estilo autorizativo, mientras que las puntuaciones más bajas correspondieron a los estilos parentales autoritario y negligente. CONCLUSIONES: Los resultados de este estudio se discuten considerando la relevancia del contexto cultural donde se produce la socialización parental

INTRODUCTION AND OBJECTIVES: This study analyzes the relationship between parental styles (indulgent, authoritative, authoritarian, and neglectful) with the short- and long-term pattern of personal and social adjustment in children, teenagers and adults. MATERIAL AND METHODS: The sample consisted of 2,119 Spanish children (59.2% female), 623 adolescents (12-18 years), 591 young adults (19-35 years), 509 middle-aged adults (36-59 years) and 396 older adults (60 years or more). Families were classified into one of four parental typologies (indulgent, authoritative, authoritarian and neglectful) based on their scores in the two main dimensions (acceptance/implication and severity/imposition). Children's personal and social adjustment was measured with family self-concept, self-esteem, aggressiveness, sexist prejudice, and internalization of social values of universalism. RESULTS: The results showed a common short- and long-term pattern between parental styles and personal and social adjustment. The indulgent style was associated with equal or even better scores on personal and social adjustment than the authoritative style, while the lower scores corresponded to the authoritarian and neglectful parental styles. CONCLUSIONS: The findings are discussed considering the relevance of the cultural context in which parental socialization occurs

Integron Identification in Bacterial Genomes and Cassette Recombination Assays.

Integrons are genetic elements involved in bacterial adaptation to the environment. Sedentary chromosomal integrons (SCIs) can stockpile and rearrange a myriad of different functions encoded in gene cassettes. Through their association with transposable elements and conjugative plasmids, some SCIs have acquired mobility and are now termed Mobile Integrons (MIs). MIs have reached the hospitals and are involved in the rise and spread of antibiotic resistance genes through horizontal gene transfer among numerous bacterial species. Here we aimed at describing methods for the detection of integrons in sequenced bacterial genomes as well as for the experimental characterization of the activity of their different components: the integrase and the recombination sites.

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

Multicopy plasmids are extremely abundant in prokaryotes but their role in bacterial evolution remains poorly understood. We recently showed that the increase in gene copy number per cell provided by multicopy plasmids could accelerate the evolution of plasmid-encoded genes. In this work, we present an experimental system to test the ability of multicopy plasmids to promote gene evolution. Using simple molecular biology methods, we constructed a model system where an antibiotic resistance gene can be inserted into Escherichia coli MG1655, either in the chromosome or on a multicopy plasmid. We use an experimental evolution approach to propagate the different strains under increasing concentrations of antibiotics and we measure survival of bacterial populations over time. The choice of the antibiotic molecule and the resistance gene is so that the gene can only confer resistance through the acquisition of mutations. This "evolutionary rescue" approach provides a simple method to test the potential of multicopy plasmids to promote the acquisition of antibiotic resistance. In the next step of the experimental system, the molecular bases of antibiotic resistance are characterized. To identify mutations responsible for the acquisition of antibiotic resistance we use deep DNA sequencing of samples obtained from whole populations and clones. Finally, to confirm the role of the mutations in the gene under study, we reconstruct them in the parental background and test the resistance phenotype of the resulting strains.

Genomic Plasticity of Vibrio cholerae

Vibrio cholerae is one of the deadliest pathogens in the history of humankind. It is the causative agent of cholera, a disease characterized by a profuse and watery diarrhoea that still today causes 95.000 deaths worldwide every year. V. cholerae is a free living marine organism that interacts with and infects a variety of organisms, from amoeba to humans, including insects and crustaceans. The complexity of the lifestyle and ecology of V. cholerae suggests a high genetic and phenotypic plasticity. In this review, we will focus on two peculiar genomic features that enhance genetic plasticity in this bacterium: the division of its genome in two different chromosomes and the presence of the superintegron, a gene capture device that acts as a large, low-cost memory of adaptive functions, allowing V. cholerae to adapt rapidly (AU)

No disponible

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

In this study, we characterized two tigecycline-resistant Klebsiella pneumoniae isolates from dog urine samples. The isolates were genetically unrelated, belonging to sequence type 11 (ST11) and ST147, both classically related to human isolates. To the best of our knowledge, this is the first identification of tigecycline-resistant isolates from animals. We unveil here the worrisome circulation among animals of bacterial clones resistant to this last-resort antibiotic.

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

Integrons ensure a rapid and "on demand" response to environmental stresses driving bacterial adaptation. They are able to capture, store, and reorder functional gene cassettes due to site-specific recombination catalyzed by their integrase. Integrons can be either sedentary and chromosomally located or mobile when they are associated with transposons and plasmids. They are respectively called sedentary chromosomal integrons (SCIs) and mobile integrons (MIs). MIs are key players in the dissemination of antibiotic resistance genes. Here, we used in silico and in vivo approaches to study cassette excision dynamics in MIs and SCIs. We show that the orientation of cassette arrays relative to replication influences attC site folding and cassette excision by placing the recombinogenic strands of attC sites on either the leading or lagging strand template. We also demonstrate that stability of attC sites and their propensity to form recombinogenic structures also regulate cassette excision. We observe that cassette excision dynamics driven by these factors differ between MIs and SCIs. Cassettes with high excision rates are more commonly found on MIs, which favors their dissemination relative to SCIs. This is especially true for SCIs carried in the Vibrio genus, where maintenance of large cassette arrays and vertical transmission are crucial to serve as a reservoir of adaptive functions. These results expand the repertoire of known processes regulating integron recombination that were previously established and demonstrate that, in terms of cassette dynamics, a subtle trade-off between evolvability and genetic capacitance has been established in bacteria.IMPORTANCE The integron system confers upon bacteria a rapid adaptation capability in changing environments. Specifically, integrons are involved in the continuous emergence of bacteria resistant to almost all antibiotic treatments. The international situation is critical, and in 2050, the annual number of deaths caused by multiresistant bacteria could reach 10 million, exceeding the incidence of deaths related to cancer. It is crucial to increase our understanding of antibiotic resistance dissemination and therefore integron recombination dynamics to find new approaches to cope with the worldwide problem of multiresistance. Here, we studied the dynamics of recombination and dissemination of gene encoding cassettes carried on integrons. By combining in silico and in vivo analyses, we show that cassette excision is highly regulated by replication and by the intrinsic properties of cassette recombination sites. We also demonstrated differences in the dynamics of cassette recombination between mobile and sedentary chromosomal integrons (MIs and SCIs). For MIs, a high cassette recombination rate is favored and timed to conditions when generating diversity (upon which selection can act) allows for a rapid response to environmental conditions and stresses. In contrast, for SCIs, cassette excisions are less frequent, limiting cassette loss and ensuring a large pool of cassettes. We therefore confirm a role of SCIs as reservoirs of adaptive functions and demonstrate that the remarkable adaptive success of integron recombination system is due to its intricate regulation.

Genomic Plasticity of Vibrio cholerae.

Vibrio cholerae is one of the deadliest pathogens in the history of humankind. It is the causative agent of cholera, a disease characterized by a profuse and watery diarrhoea that still today causes 95.000 deaths worldwide every year. V. cholerae is a free living marine organism that interacts with and infects a variety of organisms, from amoeba to humans, including insects and crustaceans. The complexity of the lifestyle and ecology of V. cholerae suggests a high genetic and phenotypic plasticity. In this review, we will focus on two peculiar genomic features that enhance genetic plasticity in this bacterium: the division of its genome in two different chromosomes and the presence of the superintegron, a gene capture device that acts as a large, low-cost memory of adaptive functions, allowing V. cholerae to adapt rapidly.

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

The integron is a bacterial recombination system that allows acquisition, stockpiling and expression of cassettes carrying protein-coding sequences, and is responsible for the emergence and rise of multiresistance in Gram-negative bacteria. The functionality of this system depends on the insertion of promoterless cassettes in correct orientation, allowing their expression from the promoter located upstream of the cassette array. Correct orientation is ensured by strand selectivity of integron integrases for the bottom strand of cassette recombination sites (attC), recombined in form of folded single-stranded hairpins. Here, we investigated the basis of such strand selectivity by comparing recombination of wild-type and mutated attC sites with different lengths, sequences and structures. We show that all three unpaired structural features that distinguish the bottom and top strands contribute to strand selectivity. The localization of Extra-Helical Bases (EHBs) directly favors integrase binding to the bottom strand. The Unpaired Central Spacer (UCS) and the Variable Terminal Structure (VTS) influence strand selectivity indirectly, probably through the stabilization of the bottom strand and the resulting synapse due to the nucleotide skew between the two strands. These results underscore the importance of the single-stranded nature of the attC site that allows such tight control over integron cassette orientation.

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

Tyrosine (Y)-recombinases have evolved to deliver mechanistically different reactions on a variety of substrates, but these evolutionary transitions are poorly understood. Among them, integron integrases are hybrid systems recombining single- and double-stranded DNA partners. These reactions are asymmetric and need a replicative resolution pathway, an exception to the canonical second strand exchange model of Y-recombinases. Integron integrases possess a specific domain for this specialized pathway. Here we show that despite this, integrases are still capable of efficiently operating the ancestral second strand exchange in symmetrical reactions between double-stranded substrates. During these reactions, both strands are reactive and Holliday junction resolution can follow either pathway. A novel deep-sequencing approach allows mapping of the crossover point for the second strand exchange. The persistence of the ancestral activity in integrases illustrates their robustness and shows that innovation towards new recombination substrates and resolution pathways was a smooth evolutionary process.

Multicopy plasmids potentiate the evolution of antibiotic resistance in bacteria.

Plasmids are thought to play a key role in bacterial evolution by acting as vehicles for horizontal gene transfer, but the role of plasmids as catalysts of gene evolution remains unexplored. We challenged populations of Escherichia coli carrying the blaTEM-1 ß-lactamase gene on either the chromosome or a multicopy plasmid (19 copies per cell) with increasing concentrations of ceftazidime. The plasmid accelerated resistance evolution by increasing the rate of appearance of novel TEM-1 mutations, thereby conferring resistance to ceftazidime, and then by amplifying the effect of TEM-1 mutations due to the increased gene dosage. Crucially, this dual effect was necessary and sufficient for the evolution of clinically relevant levels of resistance. Subsequent evolution occurred by mutations in a regulatory RNA that increased the plasmid copy number, resulting in marginal gains in ceftazidime resistance. These results uncover a role for multicopy plasmids as catalysts for the evolution of antibiotic resistance in bacteria.

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

BACKGROUND: Carbapenemases are a major concern for the treatment of infectious diseases caused by Gram-negative bacteria. Although plasmids are responsible for the spread of resistance genes among these pathogens, there is limited information on the nature of the mobile genetic elements carrying carbapenemases in Pseudomonas aeruginosa. METHODS: We combined data from two different next-generation sequencing platforms, Illumina HiSeq2000 and PacBio RSII, to obtain the complete nucleotide sequences of two blaVIM-1-carrying plasmids (pAMBL1 and pAMBL2) isolated from P. aeruginosa clinical isolates. RESULTS: Plasmid pAMBL1 has 26 440 bp and carries a RepA_C family replication protein. pAMBL1 is similar to plasmids pNOR-2000 and pKLC102 from P. aeruginosa and pAX22 from Achromobacter xylosoxidans, which also carry VIM-type carbapenemases. pAMBL2 is a 24 133 bp plasmid with a replication protein that belongs to the Rep_3 family. It shows a high degree of homology with a fragment of the blaVIM-1-bearing plasmid pPC9 from Pseudomonas putida. Plasmid pAMBL2 carries three copies of the blaVIM-1 cassette in an In70 class 1 integron conferring, unlike pAMBL1, high-level resistance to carbapenems. CONCLUSIONS: We present two new plasmids coding for VIM-1 carbapenemase from P. aeruginosa and report that the presence of three copies of blaVIM-1 in pAMBL2 produces high-level resistance to carbapenems.

The Integron: Adaptation On Demand.

The integron is a powerful system which, by capturing, stockpiling, and rearranging new functions carried by gene encoding cassettes, confers upon bacteria a rapid adaptation capability in changing environments. Chromosomally located integrons (CI) have been identified in a large number of environmental Gram-negative bacteria. Integron evolutionary history suggests that these sedentary CIs acquired mobility among bacterial species through their association with transposable elements and conjugative plasmids. As a result of massive antibiotic use, these so-called mobile integrons are now widespread in clinically relevant bacteria and are considered to be the principal agent in the emergence and rise of antibiotic multiresistance in Gram-negative bacteria. Cassette rearrangements are catalyzed by the integron integrase, a site-specific tyrosine recombinase. Central to these reactions is the single-stranded DNA nature of one of the recombination partners, the attC site. This makes the integron a unique recombination system. This review describes the current knowledge on this atypical recombination mechanism, its implications in the reactions involving the different types of sites, attC and attI, and focuses on the tight regulation exerted by the host on integron activity through the control of attC site folding. Furthermore, cassette and integrase expression are also highly controlled by host regulatory networks and the bacterial stress (SOS) response. These intimate connections to the host make the integron a genetically stable and efficient system, granting the bacteria a low cost, highly adaptive evolution potential "on demand".