Transfer and Persistence of a Multi-Drug Resistance Plasmid in situ of the Infant Gut Microbiota in the Absence of Antibiotic Treatment

Gumpert, Heidi; Kubicek-Sutherland, Jessica Z.; Porse, Andreas; Karami, Nahid; Munck, Christian; Linkevičius, Marius; Adlerberth, Ingegerd; Wold, Agnes E.; Andersson, Dan I.; Sommer, Morten Otto Alexander

doi:10.3389/fmicb.2017.01852

Cited by 70 publications

(55 citation statements)

References 52 publications

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“…Capturing HGT events from natural microbial communities. Extensive HGT has been reported in the human microbiome and has been shown to facilitate the spread of clinically important genes such as antibiotic resistance genes 3,4,[38][39][40] . Therefore, we sought to identify mobile DNA accessible to E. coli in clinically relevant human fecal microbiomes.…”

Section: Resultsmentioning

confidence: 99%

Recording mobile DNA in the gut microbiota using an Escherichia coli CRISPR-Cas spacer acquisition platform

et al. 2020

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The flow of genetic material between bacteria is central to the adaptation and evolution of bacterial genomes. However, our knowledge about DNA transfer within complex microbiomes is lacking, with most studies of horizontal gene transfer (HGT) relying on bioinformatic analyses of genetic elements maintained on evolutionary timescales or experimental measurements of phenotypically trackable markers. Here, we utilize the CRISPR-Cas spacer acquisition process to detect DNA acquisition events from complex microbiota in real-time and at nucleotide resolution. In this system, an E. coli recording strain is exposed to a microbial sample and spacers are acquired from transferred plasmids and permanently stored in genomic CRISPR arrays. Sequencing and analysis of acquired spacers enables identification of the transferred plasmids. This approach allowed us to identify individual mobile elements without relying on phenotypic markers or post-transfer replication. We found that HGT into the recording strain in human clinical fecal samples can be extensive and is driven by different plasmid types, with the IncX type being the most actively transferred.

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Section: Resultsmentioning

confidence: 99%

Recording mobile DNA in the gut microbiota using an Escherichia coli CRISPR-Cas spacer acquisition platform

et al. 2020

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“…In an infant treated with multiple antibiotics, 2 months were required before antimicrobial resistance emerged within speci c bacterial lineages [26,27]. In a similar study, novel plasmid-mediated ampicillin resistance was acquired after 16-32 days in the absence of antibiotic treatment [28]. The implication is that resistance within complex human systems such as the gut arises over weeks instead of days [7].…”

Section: Discussionmentioning

confidence: 97%

The effect of short-course antibiotics on the resistance profile of colonizing gut bacteria in the ICU: a prospective cohort study

Munck

Sheth

Cuaresma

et al. 2020

Preprint

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Background : The need for early antibiotics in the intensive care unit (ICU) is often balanced against the goal of antibiotic stewardship. Long-course antibiotics increase the burden of antimicrobial resistance within colonizing gut bacteria, but the dynamics of this process are not fully understood. We sought to determine how short-course antibiotics affect the antimicrobial resistance phenotype and genotype of colonizing gut bacteria in the ICU by performing a prospective cohort study with assessments of resistance at ICU admission and exactly 72 hours later. Methods : Deep rectal swabs were performed on 48 adults at the time of ICU admission and exactly 72 hours later, including patients who did and did not receive antibiotics. To determine resistance phenotype, rectal swabs were cultured for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). In addition, Gram-negative bacterial isolates were cultured against relevant antibiotics. To determine resistance genotype, quantitative PCR (qPCR) was performed from rectal swabs for 87 established resistance genes. Within-individual changes in antimicrobial resistance were calculated based on culture and qPCR results and correlated with exposure to relevant antibiotics (e.g., did β-lactam antibiotic exposure associate with a detectable change in β-lactam resistance over this 72-hour period?). Results : Of 48 ICU patients, 41 (85%) received antibiotics. Overall, there was no increase in the antimicrobial resistance profile of colonizing gut bacteria during the 72 hour study period. There was also no increase in antimicrobial resistance after stratification by receipt of antibiotics (i.e., no detectable increase in β-lactam, vancomycin, or macrolide resistance regardless of whether patients received those same antibiotics). This was true for both culture and PCR. Antimicrobial resistance pattern at ICU admission strongly predicted resistance pattern after 72 hours. Conclusions . Short-course ICU antibiotics made little detectable difference in the antimicrobial resistance pattern of colonizing gut bacteria over 72 hours in the ICU. This provides improved understanding of the dynamics of antimicrobial resistance in the ICU and some reassurance that short-course antibiotics may not adversely impact the stewardship goal of reducing antimicrobial resistance.

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“…Antibiotic stress can result in sensitive bacteria evolving resistance mechanisms by selecting for gene variants that confer higher resistance [14,15]. Importantly, ARGs can also be transferred within and between species [16], particularly in complex microbial communities such as the gut [17,18].…”

Section: Introductionmentioning

confidence: 99%

Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment

Kang

Imamovic

Misiakou

et al. 2020

Preprint

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Background. Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes on the human gut microbiome are often investigated in cohorts with pre-existing health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood.Results. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologues did not significantly change, antibiotic-specific gene homologues with presumed resistance towards the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed the expansion of antibiotic-specific resistance gene homologues even three months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species.Conclusions. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.

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Transfer and Persistence of a Multi-Drug Resistance Plasmid in situ of the Infant Gut Microbiota in the Absence of Antibiotic Treatment

Cited by 70 publications

References 52 publications

Recording mobile DNA in the gut microbiota using an Escherichia coli CRISPR-Cas spacer acquisition platform

Recording mobile DNA in the gut microbiota using an Escherichia coli CRISPR-Cas spacer acquisition platform

The effect of short-course antibiotics on the resistance profile of colonizing gut bacteria in the ICU: a prospective cohort study

Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment

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