Even though patients are treated with in vitro effective drugs, infection relapses often occur. Treatment failure is not only associated with antibiotic resistance but also with persistence. Resistant bacteria continue to grow in the presence of antibiotics and pass the genetic resistance-determinant on to their progeny. In contrast, persistence describes a temporary tolerance towards antibiotics. Division of these persisting bacteria results in an antibiotic susceptible population again.
This phenomenon was firstly described by Joseph Bigger in 1944 (Bigger, Lancet, 1944). He observed that 99 % of a Staphylococcus aureus culture was killed by penicillin and defined the surviving 1 % of bacteria as persisters. Persisters are non-growing bacterial cells that enter a dormant state, rendering currently available antibiotics ineffective.
We aim to identify host factors responsible for persister formation. Since relapsing infections are often associated with abscesses, which are characterized by low pH, we investigated the effect of pH on Staphylococcus aureus persister formation. Indeed, we found that low pH favored the formation of this dormant phenotype (Leimer, JID, 2015).
Abscesses are usually treated by surgical removal. Besides abscesses, other low pH compartments exist in every host cell, the lysosomes. Staphylococcus aureus can invade host cells and survive in the harsh environment of lysosomes by entering into the persister state. In contrast to abscesses, intracellular bacteria cannot be mechanically removed and often resist eradication by currently available antibiotics. Thus, alternative treatment strategies are needed. By increasing the pH of the lysosomes, bacteria resume growth and are sensitized to antimicrobial therapy (Leimer, JID, 2015).
This knowledge should help to further optimize antibiotic regimes for treating chronic Staphylococcus aureus infections and identify other virulence factors responsible for recurrent infections.
Intracellular persistence of Staphylococcus aureus within phagolysosomes. Host cells were infected with S. aureus and extracellular bacteria were killed by antibiotics. The intracellular localization of bacteria (green) was analyzed by fluorescence microscopy. Lysosomes appear in red and DNA in blue.
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Department of Infectious Disease and Hospital Epidemiology
University Hospital Zurich