Horizontal gene transfer and ecological interactions jointly control microbiome stability.

Genes encoding resistance to stressors, such as antibiotics or environmental pollutants, are widespread across microbiomes, often encoded on mobile genetic elements. Yet, despite their prevalence, the impact of resistance genes and their mobility upon the dynamics of microbial communities remains largely unknown. Here we develop eco-evolutionary theory to explore how resistance genes alter the stability of diverse microbiomes in response to stressors. We show that adding resistance genes to a microbiome typically increases its overall stability, particularly for genes on mobile genetic elements with high transfer rates that efficiently spread resistance throughout the community. However, the impact of resistance genes upon the stability of individual taxa varies dramatically depending upon the identity of individual taxa, the mobility of the resistance gene, and the network of ecological interactions within the community. Nonmobile resistance genes can benefit susceptible taxa in cooperative communities yet damage those in competitive communities. Moreover, while the transfer of mobile resistance genes generally increases the stability of previously susceptible recipient taxa to perturbation, it can decrease the stability of the originally resistant donor taxon. We confirmed key theoretical predictions experimentally using competitive soil microcosm communities. Here the stability of a susceptible microbial community to perturbation was increased by adding mobile resistance genes encoded on conjugative plasmids but was decreased when these same genes were encoded on the chromosome. Together, these findings highlight the importance of the interplay between ecological interactions and horizontal gene transfer in driving the eco-evolutionary dynamics of diverse microbiomes.

Plasmid stability is enhanced by higher-frequency pulses of positive selection.

Plasmids accelerate bacterial adaptation by sharing ecologically important traits between lineages. However, explaining plasmid stability in bacterial populations is challenging owing to their associated costs. Previous theoretical and experimental studies suggest that pulsed positive selection may explain plasmid stability by favouring gene mobility and promoting compensatory evolution to ameliorate plasmid cost. Here we test how the frequency of pulsed positive selection affected the dynamics of a mercury-resistance plasmid, pQBR103, in experimental populations of Pseudomonas fluorescens SBW25. Plasmid dynamics varied according to the frequency of Hg2+ positive selection: in the absence of Hg2+ plasmids declined to low frequency, whereas pulses of Hg2+ selection allowed plasmids to sweep to high prevalence. Compensatory evolution to ameliorate the cost of plasmid carriage was widespread across the entire range of Hg2+ selection regimes, including both constant and pulsed Hg2+ selection. Consistent with theoretical predictions, gene mobility via conjugation appeared to play a greater role in promoting plasmid stability under low-frequency pulses of Hg2+ selection. However, upon removal of Hg2+ selection, plasmids which had evolved under low-frequency pulse selective regimes declined over time. Our findings suggest that temporally variable selection environments, such as those created during antibiotic treatments, may help to explain the stability of mobile plasmid-encoded resistance.

A rapid evidence assessment exploring whether antimicrobial resistance complicates non-infectious health conditions and healthcare services, 2010-20.

Antimicrobial resistance (AMR) is one of the greatest public health threats at this time. While there is a good understanding of the impacts of AMR on infectious diseases, an area of less focus is the effects AMR may be having on non-communicable health conditions (such as cancer) and healthcare services (such as surgery). Therefore, this study aimed to explore what impact AMR is currently having on non-communicable health conditions, or areas of health services, where AMR could be a complicating factor impacting on the ability to treat the condition and/or health outcomes. To do this, a rapid evidence assessment of the literature was conducted, involving a systematic approach to searching and reviewing the evidence. In total, 101 studies were reviewed covering surgery, organ transplants, cancer, ICUs, diabetes, paediatric patients, immunodeficiency conditions, liver and kidney disease, and physical trauma. The results showed limited research in this area and studies often use a selective population, making the results difficult to generalize. However, the evidence showed that for all health conditions and healthcare service areas reviewed, at least one study demonstrated a higher risk of death for patients with resistant infections, compared with no or drug-susceptible infections. Poor health outcomes were also associated with resistant infections in some instances, such as severe sepsis and failure of treatments, as well as a greater need for invasive medical support. While there are gaps in the evidence base requiring further research, efforts are also needed within policy and practice to better understand and overcome these challenges.

Gene mobility promotes the spread of resistance in bacterial populations.

Theory predicts that horizontal gene transfer (HGT) expands the selective conditions under which genes spread in bacterial populations. Whereas vertically inherited genes can only spread by positively selected clonal expansion, mobile genetic elements can drive fixation of genes by infectious HGT. We tested this using populations of Pseudomonas fluorescens and the conjugative mercury resistance (HgR) plasmid pQBR57. HGT expanded the selective conditions allowing the spread of HgR: Chromosomal HgR only increased in frequency under positive selection, whereas plasmid-encoded HgR reached fixation with or without positive selection. Tracking plasmid dynamics over time revealed that the mode of HgR inheritance varied across mercury environments. Under mercury selection, the spread of HgR was driven primarily by clonal expansion while in the absence of mercury HgR dynamics were dominated by infectious transfer. Thus, HGT is most likely to drive the spread of resistance genes in environments where resistance is useless.