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Type IV coupling proteins as potential targets to control the dissemination of antibiotic resistance

Authors: Álvarez-Rodríguez I, Arana L, Ugarte-Uribe B, Gómez-Rubio E, Martín-Santamaría S, Garbisu C, Alkorta I
Title: Type IV coupling proteins as potential targets to control the dissemination of antibiotic resistance
Journal:  Frontiers in Molecular Biosciences
Vol: 7, 201 Date: 2020
https://doi:10.3389/fmolb.2020.00201

The increase of infections caused by multidrug-resistant bacteria, together with the loss of effectiveness of currently available antibiotics, represents one of the most serious threats to public health worldwide. The loss of human lives and the economic costs associated to the problem of the dissemination of antibiotic resistance require immediate action. Bacteria, known by their great genetic plasticity, are capable not only of mutating their genes to adapt to disturbances and environmental changes but also of acquiring new genes that allow them to survive in hostile environments, such as in the presence of antibiotics. One of the major mechanisms responsible for the horizontal acquisition of new genes (e.g., antibiotic resistance genes) is bacterial conjugation, a process mediated by mobile genetic elements such as conjugative plasmids and integrative conjugative elements. Conjugative plasmids harboring antibiotic resistance genes can be transferred from a donor to a recipient bacterium in a process that requires physical contact. After conjugation, the recipient bacterium not only harbors the antibiotic resistance genes but it can also transfer the acquired plasmid to other bacteria, thus contributing to the spread of antibiotic resistance. Conjugative plasmids have genes that encode all the proteins necessary for the conjugation to take place, such as the type IV coupling proteins (T4CPs) present in all conjugative plasmids. Type VI coupling proteins constitute a heterogeneous family of hexameric ATPases that use energy from the ATP hydrolysis for plasmid transfer. Taking into account their essential role in bacterial conjugation, T4CPs are attractive targets for the inhibition of bacterial conjugation and, concomitantly, the limitation of antibiotic resistance dissemination. This review aims to compile present knowledge on T4CPs as a starting point for delving into their molecular structure and functioning in future studies. Likewise, the scientific literature on bacterial conjugation inhibitors has been reviewed here, in an attempt to elucidate the possibility of designing T4CP-inhibitors as a potential solution to the dissemination of multidrug-resistant bacteria.

Emergency and spread of antibiotic resistance (KONTRAE)

In the KONTRAE project (funded by ELKARTEK, Basque Government), we will study in depth the links between human health, livestock, food and environment, in relation to antibiotic resistance.

According to the World Health Organization (WHO), antibiotic resistance is currently one of the greatest threats to human health, the economic sustainability of health systems, food security and overall socio-economic development. In the Autonomous Community of the Basque Country (CAPV), as in the rest of the world, this problem is increasing in a worrying way, as reflected in the growing detection in our hospitals of infections caused by multi-resistant or pan-resistant bacteria, with the resulting increase in deaths, health costs and productivity losses for companies.

To be able to successfully face this health and economic challenge, it is essential to approach it from a One Health perspective (“healthy people, healthy animals, safe and healthy food, healthy environment”), since the emergence and dissemination of many of the resistances to antibiotics occur in the environment and, through different routes of exposure, reach people.

Links between pesticide residues and antibiotic resistance dissemination in organically-managed agroecosystems (PRADA)

The main objective of this PRADA project (PID2019-110058GB-C22, financed by the ministry of Science and Innovation) is to unravel the links between the presence of pesticide residues (copper-fungicide, glyphosate-herbicide) and animal manure-derived organic amendments (cow manure) on the emergence (resistome) and dissemination (mobilome) of antibiotic resistance (AR) in conventional and ecological agriculture systems, as well as to better understand the potential contribution of relevant edaphoclimatic factors (soil pH, temperature, moisture) on such AR.

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URBAN KLIMA 2050

LIFE IP URBAN KLIMA 2050 is the largest climate action project in Basque Country for the next years and will demonstrate the effective and well-coordinated implementation of the KLIMA 2050 climate strategy in our territory. The project considers the urban settlements as the core for CC adaptation. One of the objectives is citizens’ empowerment for long-term engagement in environmentally responsible behaviours and healthier lifestyles. In this respect, our role in the project will be to take part in the design of a methodology for the creation of a platform for citizen science. This platform will include measurements from our Soil Health Cards, a tool that allows to evaluate the health of soil ecosystems in general and agroecosystems in particular, thus being able to monitor the evolution of the case studies of the project and choose those management alternatives that prove to be more sustainable from the point of view of the mitigation and adaptation to CC.

You will find more information about the project here

 

Documentary on antibiotic resistance

We have taken part in the recording of a documentary on antibiotic resistance for the Teknopolis programme of ETB. EHU/UPV, BC3 and Neiker-Tecnalia have joined forces in a pioneering research that studies the problem from different perspectives: environment, climate change, agriculture and livestock. Teknopolis has explained how resistance emerges and why it spreads, the solutions proposed by the experts and how each of us can do our bit.

In Basque: Lehen bideoa Bigarren bideoa

In Spanish: Primer vídeo Segundo vídeo

 

Design of a soil monitoring network for the Basque Country

It is increasingly recognized that soils provide multiple benefits to people, the environment and the economy, and that healthy soils are fundamental for achieving them. Soil functions include providing food, fibre and fuel, decomposing organic matter and recycling nutrients, distributing rainwater, etc. However, the soil resource and the functions it provides are constantly threatened by a wide range of risks at different scales, from local issues such as inadequate management, local pollution and erosion, to global issues such as air pollution and, of course, climate change. Furthermore, it is reasonable to assume that these risks will continue or intensify in the coming decades.

The state of soils needs to be monitored to see how they are changing and to understand the pressures on them. Soil monitoring networks can be described as: “A purpose-built set of sites to document changes in soil characteristics through periodic assessment of a broad set of soil parameters”. The use of custom-built soil monitoring networks is the most effective way to reliably assess temporary changes in soil status at the territorial level. Soil quality monitoring networks have been in operation in many European countries for years; the LURSARE project, funded by IHOBE, aims to fill this gap in the Basque Autonomous Community. In this sense, it is initially proposed to address a design phase of a soil quality monitoring programme, selecting the sampling points, depth(s), sampling frequency, soil properties to be determined, methodologies, etc.

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Final degree works using simple soil field measurements

In collaboration with Arantza Aldezabal of the University of the Basque Country, we are co-directing the final degree works of June and Olatz, on the influence of the management of valley bottom cattle farms on soil health. SMEG is particularly interested in testing new simple field measurements (e.g., bait-lamina test, Solvita, a self-designed soil respiration test, soil nutrient measurement kits, different organic matter estimates, macrofaunal taxonomic assignments). These measurements will be validated with standard laboratory tests. Let’s go for it!

Effect of biostimulant formulations on soil microbial parameters

We have started a collaboration with the company Ceres-Biotics, which works on the development of biostimulant formulations for agriculture.
Neiker’s work in collaboration with Ceres-Biotics will be to test the effect of different inoculations on soil health, through the measurement of a variety of parameters related to the activity, biomass and diversity of soil microbial communities. General parameters will be measured, but also specific parameters related to the potentiality of the strains under study.