DISTRIBUTION OF ANTIBIOTIC RESISTANCE GENES IN THE ENVIRONMENT:
THE ROLE OF MINERAL FACILITATED HORIZONTAL GENE TRANSFER
Combining recent research across disciplines, I see evidence that minerals hold a high and unrecognized potential for enhancing the distribution of the ARg in the environment. Adsorption of ARg to minerals significantly increases the ARg’s lifetime and facilitates their distribution by sedimentary transport processes. In addition, minerals also serve as a) sites for horizontal gene transfer (HGT), b) platforms for microbial growth and, hence 3) act as hot spots for propagation of adsorbed ARg to other microbes. However, some minerals and ARg are bound more strongly than others and various bacteria have different affinities toward various minerals. Those variations in affinity are poorly quantified but vital for predicting the distribution of ARg in the environment.
Bacterial colony formation.
Image by Lisselotte Jauffred (collaborator from NBI)
The spread of antibiotic resistance genes (ARg) is a worldwide health risk1 and is no longer only a clinical issue. Vast reservoirs of ARg are found in natural environments2–4 such as soils, sediments and oceans. The emergence and release of ARg to the environment is in particular caused by extended use of antibiotics in farming, e.g. where the genes dissipate from the manure.5 Once in the environment, the ARg are surprisingly rapidly propagated. It is well known that the ARg are distributed to neighbour bacteria through processes of both cell sharing or through horizontal gene transfer (HGT) where one species acquirer resistance from another.6,7 Most HGT responsible for the spread of ARg are assumed to be through direct microbe-microbe contact. However, I find that the outcome of non-contact transfer is grossly underestimated. In the HGT mechanism called “Transformation”, free ARg in suspension or adsorbed to a mineral can be picked up and incorporated into non-related organisms. Considering that free DNA only can survive for a few weeks in sea- and freshwater environments,8–10 any HGT from free DNA can rightly be assumed to be local, but if the DNA gets adsorbed to a mineral, it can survive for several hundred thousands of years.11–14 If this also holds for ARg, then minerals offer a potent mechanism for distributing ARg through our environments my means of sedimentary processes.
DYNAMIC FORCE SPECTROSCOPY
POLYMER APPROACH
Dynamic force spectroscopy can probe the free energy landscape of interacting bonds, but interpretations polymer-mineral interactions are challenged by the complex mechanical behavior of polymers. We recently restated the difficulties inherent to applying DFS to polymer-linked adhesion and present an approach to gain quantitative insight into
polymer-mineral binding.
Our formulation of a DFSpolymer approach applies to both the equilibrium and nonequilibrium regimes and it should be adapted to describe the bond behavior and binding mechanisms of elastic (bio)polymers.
Our approach add to the applicability of the DFS method to complex biopolymers and has a range of implications including bioinspired approaches to materials design and synthesis utilized such interactions to advance medical and technological applications, such as nanoparticles for ingestion, bone implants, and responsive materials.
METHOD IN SHORT:
DFSpolymer approach in short: a) A biomolecule is covalently attached to an AFM tip and brought into contact with a surface. b) By varying the ret raction velocities, we obtain 2 regimes: i) a near-equilibrium regime, where the retraction velocity is slow enough to record events of the bond formation and breaking, and where an equilibrium force can be extracted (feq). ii) a kinetic regime, where the rupture force depends asymptotically on the retraction rate from where the kinetic off-rate and distance to the transition state can be extracted. c)The technique requires 10,000s of force curves. Through a polymer extension analysis of the last rupture event of each force curve and by fitting the resulting dynamic force spectra, the mechanistic bond parameters can be extracted and insight into the energy landscape is obtained. Data from Sand et al.
