Abstract
Antibiotics can treat the acute phase of a disease, but often do not completely clear the etiologic agent, allowing the pathogen to establish persistent infection that can revive the disease in a frustrating recurrence of infection. The mechanisms that control chronic bacterial infections are complex and involve pathogen adaptations that favor survival from both host immune responses and antibiotic bactericidal activity. Often, the causative agents of persistent infections are not drug-resistant species. Instead, bacterial persister cells temporarily enter a physiological state that is refractory to different classes of antibiotics. Supplemental therapies that potentiate antibiotic bactericidal efficiency and/or immune clearance of persistent pathogenic species may greatly improve the outcome of infectious disease. Here, we discuss the various outcomes in experimental studies in which a mega-dose of the energy-boosting vitamin B3 (nicotinamide) was applied in murine models of chronic infection to stimulate immune clearance of chronic infection or as an immune prophylactic treatment against the highly infectious pathogen, Burkholderia pseudomallei. It is our intent to raise awareness of the risks associated with immune modulation therapies. There is great variance in host immune responses to pathogenic bacteria. Each immune modulation approach needs to be tailored to a well-characterized host-pathogen interaction.
Highlights
Persistence is a transient phenotypic adaptation that confers survival to a small percentage of cells in genetically identical bacterial populations [1]
Persistence greatly affects the evolution of acquired drug resistance mutations by decreasing antibiotic efficacy and generating a reservoir of surviving cells that can contribute to the onset of chronic infectious disease [2,3,4]
In many cases, relapse is caused by the same drug-sensitive pathogen that had initiated the acute phase of infection and had escaped both immune and therapeutic targeting through specific adaptation mechanisms [9,10,11]
Summary
Persistence is a transient phenotypic adaptation that confers survival to a small percentage of cells (between 0.01 and 10%) in genetically identical bacterial populations [1]. Persistence greatly affects the evolution of acquired drug resistance mutations by decreasing antibiotic efficacy and generating a reservoir of surviving cells that can contribute to the onset of chronic infectious disease [2,3,4]. Chronic illnesses range from the less malignant (e.g. nontuberculous pulmonary infection and strep throat) to the highly morbid with increased mortality rates upon relapse (e.g. latent tuberculosis and melioidosis) [5,6,7,8]. In many cases, relapse is caused by the same drug-sensitive pathogen that had initiated the acute phase of infection and had escaped both immune and therapeutic targeting through specific adaptation mechanisms [9,10,11]
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