Resistance integrons are bacterial genetic platforms that can capture and express antibiotic resistance genes embedded within gene cassettes. The capture and shuffling of gene cassettes are mediated by the integrase IntI, the expression of which is regulated by the SOS response in Escherichia coli. Gene cassettes are expressed from a common Pc promoter. Despite the clinical and environmental relevance of integrons, the selective forces responsible for their evolution and maintenance are poorly understood. Here, we conducted pairwise competition experiments in order to assess the fitness cost of class 1 integrons in E. coli. We found that integrons are low-cost structures and that their cost is further reduced by their tight regulation. We show that the SOS response prevents the expression of costly integrases whose cost is activity dependent. Thus, when an integron is repressed, its cost depends mostly on the expression of its gene cassettes array and increases with Pc strength and the number of cassettes in the array. Furthermore, different cassettes have different costs. Lastly, we showed that subinhibitory antibiotic concentrations promoted the selection of integron-carrying bacteria, especially those with a strong Pc promoter. These results provide new insights into the evolutionary dynamics of integron-carrying bacterial populations.

Background Infection prevention and control (IPC) is one of the most cost-effective interventions against antimicrobial resistance (AMR). Yet, IPC knowledge gaps often receive little prominence in AMR research agendas. In this article, we construct IPC research priorities, in order to draw attention to these critical research needs. Methods We developed a 4-step framework to identify IPC knowledge gaps from literature (narrative review). These gaps were then translated into research priorities and sent to two groups of European IPC experts for validation and critique through an online survey. Results Seventy-nine publications were retrieved from the literature review, identifying fifteen IPC research gaps. Forty-four IPC experts, clustered in two groups, vetted them. The experts classified all research gaps as medium or high priority. Overall agreement between both groups was average (Kendall’s τ = 0.43), with strong alignment on the highest priorities: (i) the assessment of organizational, socio-economic, and behavioural barriers/facilitators for the implementation of IPC programmes, (ii) the impact of overcrowding on the spread of infections and (iii) the impact of infrastructural changes, at facility level, on the reduction of infections. Feedback from experts also identified an additional research gap on the interaction between the human and hospital microbiomes. Conclusions We formulated a list of sixteen research priorities and identified three urgent needs. Now, we encourage researchers, funding agencies, policymakers and relevant stakeholders to start addressing the identified gaps.

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Antibiotic innovation is in serious jeopardy as companies continue to abandon the market due to a lack of profitability. Novel antibiotics must be used sparingly to hinder the spread of resistance, but small companies cannot survive on revenues that do not cover operational costs. When these companies either go bankrupt or move onto other therapeutic areas, these antibiotics may be no longer accessible to patients. Although significant research efforts have detailed incentives to stimulate antibiotic innovation, little attention has been paid to the financing of these incentives. In this article, we take a closer look at 4 potential financing models (diagnosis-related group carve-out, stewardship taxes, transferable exclusivity voucher, and a European-based “pay or play” model) and evaluate them from a European perspective. The attractiveness of these models and the willingness for countries to test them are currently being vetted through the European Joint Action on AMR and Healthcare-Associated Infections (EU-JAMRAI).