부산대학교 도서관

Genetically susceptible bacteria can escape the action of bactericidal antibiotics through antibiotic tolerance or persistence. However, one major difference between the two phenomena is their distinct penetrance within an isogenic population. While with antibiotic persistence, susceptible and persister cells co-exist, antibiotic tolerance affects the entire bacterial population. Here, we show that antibiotic tolerance can be achieved in numerous non-specific ways in vitro and during infection. More importantly, we highlight that, due to their impact on the entire bacterial population, these tolerance-inducing conditions completely mask persistence and the action of its molecular determinants. Finally, we show that even though tolerant populations display a high survival rate under bactericidal drug treatment, this feature comes at the cost of having impaired proliferation during infection. In contrast, persistence is a risk-limiting strategy that allows bacteria to survive antibiotic treatment without reducing the ability of the population to colonize their host. Altogether, our data emphasise that the distinction between these phenomena is of utmost importance to improve the design of more efficient antibiotic therapies. Author summary: Even if antibiotics should eradicate entirely a genetically susceptible bacterial population, some cells escape the action of the drugs. This phenomenon is assumed to cause antibiotic treatment failure and infection relapse. Antibiotic recalcitrance is known to operate either on the entire population (antibiotic tolerance) or on a subset of cells (antibiotic persistence). Here, we show how conditions that induce bacterial tolerance can mask entirely persistence and its molecular determinants in the pathogen Salmonella Typhimurium. The different fitness trade-offs associated with antibiotic tolerance and persistence have important consequences during infection. Understanding the distinct dynamics of these modes of recalcitrance will allow the design of more efficient antibiotic approaches. [ABSTRACT FROM AUTHOR]