2014/09/15 by Lucy Ternent, Ternent, Lucy, Rosemary Dyson +5 · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · Social Sciences · #92B05 #Antibiotic Resistance in Bacteria #Antibiotics Pharmacokinetics and Efficacy #Cell Behavior (q-bio.CB) #Evolution and Genetic Dynamics #Evolutionary Game Theory and Cooperation #FOS: Biological sciences #Populations and Evolution (q-bio.PE)
paper · pdf · doi:10.48550/arxiv.1409.4238
openalex publication_date 2014/09/15 · openalex created_date 2022/10/06 · openalex updated_date 2026/07/28
Bacterial resistance to antibiotic treatment is a huge concern: introduction\nof any new antibiotic is shortly followed by the emergence of resistant\nbacterial isolates in the clinic. This issue is compounded by a severe lack of\nnew antibiotics reaching the market. The significant rise in clinical\nresistance to antibiotics is especially problematic in nosocomial infections,\nwhere already vulnerable patients may fail to respond to treatment, causing\neven greater health concern. A recent focus has been on the development of\nanti-virulence drugs as a second line of defence in the treatment of\nantibiotic-resistant infections. This treatment, which weakens bacteria by\nreducing their virulence rather than killing them, should allow infections to\nbe cleared through the body's natural defence mechanisms. In this way there\nshould be little to no selective pressure exerted on the organism and, as such,\na predominantly resistant population would be unlikely to emerge. However, much\ncontroversy surrounds this approach with many believing it would not be\npowerful enough to clear existing infections, restricting its potential\napplication to prophylaxis. We have developed a mathematical model that\nprovides a theoretical framework to reveal the circumstances under which\nanti-virulence drugs may or may not be successful. We demonstrate that by\nharnessing and combining the advantages of antibiotics with those provided by\nanti-virulence drugs, given infection-specific parameters, it is possible to\nidentify treatment strategies that would efficiently clear bacterial\ninfections, while preventing the emergence of resistant subpopulations. Our\nfindings strongly support the continuation of research into anti-virulence\ndrugs and demonstrate that their applicability may reach beyond infection\nprevention.\n