Modelling the spread of plasmid-borne resistance in biofilms through horizontal gene transfer

Julien Vincent

University of Naples Federico II, via Cintia, Monte S. Angelo, 80126 Napoli (Italy)

"Modelling the spread of plasmid-borne resistance in biofilms through horizontal gene transfer"

The global spread of antibiotic microbial resistance (AMR) is an increasing health concern, and has been mainly attributed to antibiotics abuse and misuse. Dissemination of AMR is largely associated to plasmids, extrachromosomal genetic elements. As opposed to chromosomal resistance, plasmid-carried resistance is able to transfer to new host cells through conjugation, which plays a crucial role in the ecological success of plasmids in bacterial communities. The regulation of gene expression allowing conjugation is hypothesized to be a negative auto-regulation mechanism depending on environmental conditions. This explains how even sub-inhibitory concentrations of metals or contaminants can promote conjugation, and hence the dissemination of AMR. However, in the absence of selective pressure, this ecological success contrasts with the high costs of plasmid maintenance and very low rates of conjugation, generating the so called plasmid paradox. Biofilms are sessile bacterial communities and have been identified as a hotspot for conjugation, due to the high bacterial density allowing physical proximity of plasmid carrying bacteria and potential donors. This study presents a mathematical model simulating the social behaviour of bacteria regulating plasmid transfer under selective pressure from metals and more specifically in the case of co-resistance and cross-resistance to antibiotics and metals within a growing biofilm. The model is formulated as a nonlocal system of hybrid PDEs with a convolution integral modelling the regulation of transfer genes expression. Gene expression is modelled as a rate depending on the presence of potential receptors around a donor, called recipient-sensing. A promotion function is also introduced to account for the increase in conjugation in the presence of trace metals or inhibition when metals interfere with gene expression, based on experimental results from literature. This mathematical ecology study aims to give an insight into how bacterial social behaviour might answer the plasmid paradox, and how metal contamination participates in the spread of AMR. Numerical simulations showed that the model is able to qualitatively reproduce the influence of conjugation on plasmid dynamics in a growing biofilm. The relative influence of conjugation and vertical gene transfer was compared, including under selective pressure exerted by trace metals.
Additional authors: Alberto Tenore (Department of Mathematics and Applications 'Renato Caccioppoli', University of Naples 'Federico II', via Cintia, Monte S. Angelo, 80126 Napoli (Italy)); Maria Rosaria Mattei (Department of Mathematics and Applications 'Renato Caccioppoli', University of Naples 'Federico II', via Cintia, Monte S. Angelo, 80126 Napoli (Italy));Luigi Frunzo (Department of Mathematics and Applications 'Renato Caccioppoli', University of Naples 'Federico II', via Cintia, Monte S. Angelo, 80126 Napoli (Italy))

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