Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Tuesday Speaker Abstracts

THE EVOLUTION OF BACTERIAL ADAPTATION PHENOMENA TO ANTIMICROBIAL NANOPARTICLE Cindy Gunawan 1 ; Elizabeth Valentin 1 ; Riti Mann 1 ; Oliver McNeilly 1 ; Georgios Sotiriou 2 ; Mehrad Hamidian 1 ; Scott A Rice 3 ; 1 University of Technology Sydney, Australian Institute for Microbiology and Infection, Sydney, Australia 2 Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology, Stockholm, Sweden 3 Nanyang Technological University, Singapore Centre on Environmental Life Sciences Engineering, Singapore, Singapore Silver nanoparticle (NAg) with its broad spectrum antimicrobial efficacy has been used as alternative technologies to control pathogenic growth. NAg has been used in medical devices to fight infections, however, the nanoparticle has also been incorporated in arrays of consumer products, often without clear antimicrobial targets. This widespread use of NAg has caused concerns, as whether, just like in the case of antibiotics, bacteria will develop resistance to the important antimicrobial.Methods. Bacterial pathogens, in their free-living and biofilm forms of growth, were subjected to long-term exposures (30-50 days) to increasing NAg concentrations. The development of adaptation phenotypes were determined by assessing the changes in the nanoparticle minimum inhibition concentration (MIC) for resistance trait, as well as in the minimum duration for killing (MDK) 99% and 99.99% of the cell population for tolerance and persistence trait, respectively. Molecular basis studies (gene mutations, RNAseq, metabolomics) were carried out for insights into the adaptation mechanisms. Our study found that bacteria has the natural ability to adapt to the complex toxicity mechanisms of NAg. The nanoparticle targets multiple cellular components through the activity of the leached soluble silver and the solid silver particulates. Gram-positive and Gram-negative bacteria can develop stable resistance traits to NAg as a result of prolonged exposures, and grow in an otherwise toxic concentrations of the nanoparticle. The team found that bacteria modify their physiological growth behaviour and stress responses, which are linked to mutations in their genomes. The mutations are indicated to alter the expression levels of specific genes, affecting the cellular defence pathways. The discoveries present the need to elucidate and target the cellular signalling mechanisms that trigger the defence pathways, ultimately overcoming the adaptation phenomena. With no development of new antibiotics over the last 30 years, we need to preserve the efficacies of existing antimicrobials.

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