Publications by authors named "Alvaro San-Millan"

Article Synopsis
  • Conjugative plasmids like pOXA-48 contribute to the spread and evolution of antimicrobial resistance in bacteria, but can also cause fitness costs to their host.
  • Using transcriptomics, researchers found that the acquisition of pOXA-48 by multidrug-resistant enterobacteria leads to both unique and shared changes in gene expression, particularly affecting a chromosomal operon in certain bacteria.
  • This crosstalk is mediated by a LysR regulator encoded by the plasmid, which enhances the fitness of K. pneumoniae with pOXA-48, indicating that this mechanism may aid in the spread of carbapenem resistance in clinical environments.
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Integrons are genetic elements that increase the evolvability of bacteria by capturing new genes and stockpiling them in arrays. Sedentary chromosomal integrons (SCIs) can be massive and highly stabilized structures encoding hundreds of genes, whose function remains generally unknown. SCIs have co-evolved with the host for aeons and are highly intertwined with their physiology from a mechanistic point of view.

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Plasmids are extrachromosomal genetic elements commonly found in bacteria. They are known to fuel bacterial evolution through horizontal gene transfer, and recent analyses indicate that they can also promote intragenomic adaptations. However, the role of plasmids as catalysts of bacterial evolution beyond horizontal gene transfer is poorly explored.

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Plasmids are extrachromosomal genetic elements commonly found in bacteria. Plasmids are known to fuel bacterial evolution through horizontal gene transfer (HGT), but recent analyses indicate that they can also promote intragenomic adaptations. However, the role of plasmids as catalysts of bacterial evolution beyond HGT remains poorly explored.

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Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, β-lactam resistance genes -encoding β-lactamases- stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed.

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The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance.

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Antimicrobial resistance (AMR) in bacteria is a major public health threat and conjugative plasmids play a key role in the dissemination of AMR genes among bacterial pathogens. Interestingly, the association between AMR plasmids and pathogens is not random and certain associations spread successfully at a global scale. The burst of genome sequencing has increased the resolution of epidemiological programs, broadening our understanding of plasmid distribution in bacterial populations.

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Article Synopsis
  • - Integrons act as genetic platforms that can acquire new genes from integron cassettes (ICs), forming arrays that enhance adaptability; ICs usually rely on an adjacent promoter (Pc) for expression, functioning like an operon.
  • - Research on 29 gene-less cassettes in Vibrio species revealed that many possess promoter activity, boosting the expression of nearby cassettes; transcription start sites for these gene-less ICs were identified through a specific method (5'-RACE).
  • - The study found that gene-less cassettes in Vibrio cholerae can activate silent cassettes, significantly increasing trimethoprim resistance, while one cassette with an antisense promoter can decrease resistance, highlighting their
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Article Synopsis
  • * Research shows that pOXA-48-associated AMR and conjugation rates vary significantly among different enterobacterial strains, with some strains exhibiting higher levels than others.
  • * A mathematical model developed from this experimental data suggests that a few bacterial clones, which display high AMR and conjugation rates, are key to maintaining the spread of plasmids like pOXA-48 in diverse bacterial communities.
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Antimicrobial resistance (AMR) in bacteria is a major public health problem. The main route for AMR acquisition in clinically important bacteria is the horizontal transfer of plasmids carrying resistance genes. AMR plasmids allow bacteria to survive antibiotics, but they also entail physiological alterations in the host cell.

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Epistasis refers to the way in which genetic interactions between some genetic loci affect phenotypes and fitness. In this study, we propose the concept of "structural epistasis" to emphasize the role of the variable physical interactions between molecules located in particular spaces inside the bacterial cell in the emergence of novel phenotypes. The architecture of the bacterial cell (typically Gram-negative), which consists of concentrical layers of membranes, particles, and molecules with differing configurations and densities (from the outer membrane to the nucleoid) determines and is in turn determined by the cell shape and size, depending on the growth phases, exposure to toxic conditions, stress responses, and the bacterial environment.

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Antimicrobial resistance (AMR) in bacteria is a major threat to public health; one of the key elements in the spread and evolution of AMR in clinical pathogens is the transfer of conjugative plasmids. The drivers of AMR evolution have been studied extensively in vitro but the evolution of plasmid-mediated AMR in vivo remains poorly explored. Here, we tracked the evolution of the clinically relevant plasmid pOXA-48, which confers resistance to the last-resort antibiotics carbapenems, in a large collection of enterobacterial clones isolated from the gut of hospitalized patients.

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Antimicrobial resistance (AMR) is currently one of the most concerning threats in public health. The efforts to tackle the problem require a global One Health approach, using multidisciplinary approaches and a thorough understanding of the topic both by the general public and the experts. Currently, the lack of a shared mental model of the problem, the absence of a sense of responsibility amongst the different actors and a deficient education on the topic burden the efforts to slow down the emergency and spread of antimicrobial resistant infections.

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Objectives: To investigate the fitness effects of large blaCTX-M-15-harbouring F2:A1:B- plasmids on their native Escherichia coli ST131 H30Rx hosts.

Methods: We selected five E. coli ST131 H30Rx isolates of diverse origin, each carrying an F2:A1:B- plasmid with the blaCTX-M-15 gene.

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Plasmids are key drivers of bacterial evolution because they are crucial agents for the horizontal transfer of adaptive traits, such as antibiotic resistance. Most plasmids entail a metabolic burden that reduces the fitness of their host if there is no selection for plasmid-encoded genes. It has been hypothesized that the translational demand imposed by plasmid-encoded genes is a major mechanism driving the fitness cost of plasmids.

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With plasmid-mediated antibiotic resistance thriving and threatening to become a serious public health problem, it is paramount to increase our understanding of the forces that enable the spread and maintenance of drug resistance genes encoded in mobile genetic elements. The relevance of plasmids as vehicles for the dissemination of antibiotic resistance genes, in addition to the extensive use of plasmid-derived vectors for biotechnological and industrial purposes, has promoted the in-depth study of the molecular mechanisms controlling multiple aspects of a plasmids' life cycle. This body of experimental work has been paralleled by the development of a wealth of mathematical models aimed at understanding the interplay between transmission, replication, and segregation, as well as their consequences in the ecological and evolutionary dynamics of plasmid-bearing bacterial populations.

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Conjugation has classically been considered the main mechanism driving plasmid transfer in nature. Yet bacteria frequently carry so-called non-transmissible plasmids, raising questions about how these plasmids spread. Interestingly, the size of many mobilisable and non-transmissible plasmids coincides with the average size of phages (~40 kb) or that of a family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs, ~11 kb).

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The horizontal transfer of mobile DNA is one of the signature moves of bacterial evolution, but the specific rules that govern this transfer remain elusive. In this PLOS Biology issue, Haudiquet and colleagues revealed that the interactions between mobile genetic elements and the bacterial capsule shape the horizontal flow of DNA in an important bacterial pathogen.

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Plasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the fitness effects of the major antibiotic resistance plasmid pOXA-48_K8 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota.

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Infections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood.

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Collateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations.

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Plasmids have a key role in bacterial ecology and evolution because they mobilize accessory genes by horizontal gene transfer. However, recent studies have revealed that the evolutionary impact of plasmids goes above and beyond their being mere gene delivery platforms. Plasmids are usually kept at multiple copies per cell, producing islands of polyploidy in the bacterial genome.

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Article Synopsis
  • Mobile genetic elements (MGEs), like plasmids, facilitate bacterial evolution through horizontal gene transfer, but their trait repertoire rules were unclear.
  • The study reveals that genetic dominance influences which mutations thrive in MGEs, favoring dominant mutations and silencing recessive ones, especially in the context of antibiotic resistance.
  • These insights enhance our understanding of MGE evolution and provide a framework for predicting the spread of important traits, such as antibiotic resistance and virulence.
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Bacterial plasmids harboring antibiotic resistance genes are critical in the spread of antibiotic resistance. It is known that plasmids differ in their kinetic values, i.e.

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