Infection and Drug Resistance (Oct 2022)
Toxin-Antitoxin Systems: A Key Role on Persister Formation in Salmonella enterica Serovar Typhimurium
Abstract
Made Rai Dwitya Wiradiputra,1,2 Piyatip Khuntayaporn,1,3 Krit Thirapanmethee,1,3 Mullika Traidej Chomnawang1,3 1Antimicrobial Resistance Interdisciplinary Group (AmRIG), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 2Biopharmaceutical Sciences Program, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 3Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, ThailandCorrespondence: Mullika Traidej Chomnawang, Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand, Tel +66 2 644 8692, Email [email protected]: The toxin and antitoxin modules in bacteria consist of a toxin molecule that has activity to inhibit various cellular processes and its cognate antitoxin that neutralizes the toxin. This system is considered taking part in the formation of persister cells, which are a subpopulation of recalcitrant cells able to survive antimicrobial treatment without any resistance mechanisms. Importantly, persisters have been associated with long-term infections and treatment failures in healthcare settings. It is a public health concern since persisters can be involved in the evolution and dissemination of antimicrobial resistance amidst the aggravating spread of multidrug-resistant bacteria and insufficient novel antimicrobial therapy to tackle this issue. Salmonella enterica serovar Typhimurium is one of the most prevalent Salmonella serotypes in the world and is a leading cause of food-borne salmonellosis. S. Typhimurium has been known to cause persistent infection and a wealth of investigations on Salmonella persisters indicates that toxin and antitoxin modules play a role in mediating the phenotypic switch of persisters, rendering its survival ability in the presence of antimicrobial agents. In this review, we discuss findings regarding mechanisms that underly persistence in S. Typhimurium, especially the involvement of toxin and antitoxin modules.Keywords: toxin, antitoxin, antimicrobial resistance, persisters, Salmonella