Antibiotic effects on mitochondrial translation and in patients with mitochondrial translational defects

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Mitochondrial respiratory chain defects in infants often mimic bacterial infections, leading to antibiotic use.
• The potential impact of antibiotics on mitochondrial function, particularly translation, is often overlooked.
• Mitochondrial translation is crucial for cellular energy production.

Purpose of the Study:

• To investigate the effects of commonly used translation-targeted antibiotics on mitochondrial translation.
• To assess the impact of these antibiotics on patient-derived fibroblasts with mitochondrial translation defects.
• To highlight potential risks associated with antibiotic administration in this patient population.

Main Methods:

• Culturing fibroblasts from patients with mitochondrial translation defects.
• Treating fibroblasts with specific translation-targeted antibiotics.
• Measuring the effect of antibiotics on fibroblast growth.
• Assessing mitochondrial translation inhibition in vitro.

Main Results:

• Commonly used translation-targeted antibiotics adversely affected the growth of patient fibroblasts.
• These antibiotics were shown to inhibit mitochondrial translation directly in vitro.
• Fibroblasts from patients with mitochondrial translation defects showed particular sensitivity.

Conclusions:

• Translation-targeted antibiotics can negatively impact mitochondrial function.
• Patients with mitochondrial translation defects may be uniquely vulnerable to these antibiotics.
• Clinical consideration of antibiotic choice is crucial in infants presenting with symptoms suggestive of infection and potential mitochondrial disease.