The Role of ISCR1-Borne POUT Promoters in the Expression of Antibiotic Resistance Genes

Lallement, Claire; Pasternak, Cécile; Ploy, Marie-Cécile; Jové, Thomas

doi:10.3389/fmicb.2018.02579

Cited by 13 publications

(7 citation statements)

References 21 publications

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“…As with ISCR1, many other IS/ISCR are also known to increase the expression of adjacent genes through providing a promoter sequence, the creation of hybrid promoters upon insertion or the disruption of regulatory genes at the target site 4 , 50 . IS/ISCR induced high expression of a native ARG may provide the host with increased resistance to the respective antibiotic selection pressure 2 , 3 (e.g., during antibiotic treatment), such that the combination of IS/ISCR and ARG is selected for under these circumstances 51 . The genetic context of mobilized ARGs support this notion, as we observe that in many cases the ARG is located directly adjacent of the IS/ISCR and thus in reach of the respective promoters.…”

Section: Discussionmentioning

confidence: 99%

“…Mobile antibiotic resistance genes (ARGs) are associated with a variety of mobile genetic elements (MGEs) that enable these genes to spread to new hosts, even across taxonomic boundaries. Insertion sequences (ISs) 1 , 2 and IS common region (ISCR) elements 3 – 5 have been shown to provide both mobility and strong promotors for the expression of ARGs. In several cases, these are key elements for the mobilization of ARGs from a bacterial chromosome to transferable MGE, such as plasmids or conjugative transposons 6 – 8 .…”

Section: Introductionmentioning

confidence: 99%

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A framework for identifying the recent origins of mobile antibiotic resistance genes

2021

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Since the introduction of antibiotics as therapeutic agents, many bacterial pathogens have developed resistance to antibiotics. Mobile resistance genes, acquired through horizontal gene transfer, play an important role in this process. Understanding from which bacterial taxa these genes were mobilized, and whether their origin taxa share common traits, is critical for predicting which environments and conditions contribute to the emergence of novel resistance genes. This knowledge may prove valuable for limiting or delaying future transfer of novel resistance genes into pathogens. The literature on the origins of mobile resistance genes is scattered and based on evidence of variable quality. Here, we summarize, amend and scrutinize the evidence for 37 proposed origins of mobile resistance genes. Using state-of-the-art genomic analyses, we supplement and evaluate the evidence based on well-defined criteria. Nineteen percent of reported origins did not fulfill the criteria to confidently assign the respective origin. Of the curated origin taxa, >90% have been associated with infection in humans or domestic animals, some taxa being the origin of several different resistance genes. The clinical emergence of these resistance genes appears to be a consequence of antibiotic selection pressure on taxa that are permanently or transiently associated with the human/domestic animal microbiome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A framework for identifying the recent origins of mobile antibiotic resistance genes

2021

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“…Within the ISCR1 element is an ori IS (origin of replication) region that allows for rolling-circle replication and transposition of the ISCR1 element. Within the ori IS are two outward-oriented promoters (P OUT ) that have been shown to affect downstream gene expression ( 99 ). The resistant strain, TG22182, has both P OUT promoters associated with increased gene expression directly upstream of the bla PER−1 gene ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii

Roe

Williamson

Vazquez

et al. 2020

Front. Public Health

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Antimicrobial resistance (AMR) in the nosocomial pathogen, Acinetobacter baumannii, is becoming a serious public health threat. While some mechanisms of AMR have been reported, understanding novel mechanisms of resistance is critical for identifying emerging resistance. One of the first steps in identifying novel AMR mechanisms is performing genotype/phenotype association studies; however, performing these studies is complicated by the plastic nature of the A. baumannii pan-genome. In this study, we compared the antibiograms of 12 antimicrobials associated with multiple drug families for 84 A. baumannii isolates, many isolated in Arizona, USA. in silico screening of these genomes for known AMR mechanisms failed to identify clear correlations for most drugs. We then performed a bacterial genome wide association study (bGWAS) looking for associations between all possible 21-mers; this approach generally failed to identify mechanisms that explained the resistance phenotype. In order to decrease the genomic noise associated with population stratification, we compared four phylogenetically-related pairs of isolates with differing susceptibility profiles. RNA-Sequencing (RNA-Seq) was performed on paired isolates and differentially-expressed genes were identified. In these isolate pairs, five different potential mechanisms were identified, highlighting the difficulty of broad AMR surveillance in this species. To verify and validate differential expression, amplicon sequencing was performed. These results suggest that a diagnostic platform based on gene expression rather than genomics alone may be beneficial in certain surveillance efforts. The implementation of such advanced diagnostics coupled with increased AMR surveillance will potentially improve A. baumannii infection treatment and patient outcomes.

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“…Aeromonas species are primarily associated with aquatic environments, but are known to cause gastroenteritis or wound infections in humans after ingestion/contact with contaminated water, possibly triggering antibiotic use. As IS/IS CR1 can both mobilize 19 and increase expression of adjacent genes, 20 insertion next to the Aeromonas ampC may increase its responsiveness to antibiotic selection pressure. Our findings are hence consistent with the hypothesis that MOX-1, MOX-2 and MOX-9 were mobilized, selected for and transferred to species of the human microbiome during Aeromonas infections treated with β-lactams.…”

Section: Discussionmentioning

confidence: 99%

CMY-1/MOX-family AmpC β-lactamases MOX-1, MOX-2 and MOX-9 were mobilized independently from three Aeromonas species

Ebmeyer

Kristiansson

Larsson

2019

Journal of Antimicrobial Chemotherapy

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Objectives To investigate the origin of CMY-1/MOX-family β-lactamases. Methods Publicly available genome assemblies were screened for CMY-1/MOX genes. The loci of CMY-1/MOX genes were compared with respect to synteny and nucleotide identity, and subjected to phylogenetic analysis. Results The chromosomal ampC genes of several Aeromonas species were highly similar to known mobile CMY-1/MOX variants. Annotation and sequence comparison revealed nucleotide identities >98% and conserved syntenies between MOX-1-, MOX-2- and MOX-9-associated mobile sequences and the chromosomal Aeromonas sanarellii , Aeromonas caviae and Aeromonas media ampC loci. Furthermore, the phylogenetic analysis showed that MOX-1, MOX-2 and MOX-9 formed three distinct monophyletic groups with the chromosomal ampC genes of A. sanarellii , A. caviae and A. media , respectively. Conclusions Our findings show that three CMY-1/MOX-family β-lactamases were mobilized independently from three Aeromonas species and hence shine new light on the evolution and emergence of mobile antibiotic resistance genes.

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The Role of ISCR1-Borne POUT Promoters in the Expression of Antibiotic Resistance Genes

Cited by 13 publications

References 21 publications

A framework for identifying the recent origins of mobile antibiotic resistance genes

A framework for identifying the recent origins of mobile antibiotic resistance genes

Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii

CMY-1/MOX-family AmpC β-lactamases MOX-1, MOX-2 and MOX-9 were mobilized independently from three Aeromonas species

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