Mycobacterium dormancy and antibiotic tolerance within the retinal pigment epithelium of ocular tuberculosis

• DOI: 10.1128/spectrum.00788-24
• Publication Date: 2024-06-25T13:01:32Z
• Authors: Rachel Liu; Joshua N. Dang; Rhoeun Lee; Jae Jin Lee; Niranjana Kesavam...; Hossein Ameri; Narsing Rao; Hyungjin Eoh
• Keywords: ocular tuberculosis; Mycobacterium tuberculosis; chemotherapy; metabolomics; Microbiology; QR1-502; Research Article

ABSTRACT Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which the critical step for successful pathogenic cycle. In this stage , Mycobacterium tuberculosis resides inside host in dormant and antibiotic-tolerant state. Latent infection can also lead multisystemic because M. invades virtually all organs, including ocular tissues. Ocular (OTB) occurs when bacilli within tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Histological evidence suggests that retinal pigment epithelium (RPE) cells play central role immune privilege protection antibiotic effects, making them an anatomical niche invading . RPE exhibit high tolerance environmental redox stresses, allowing phagocytosed maintain viability However, microbiological metabolic mechanisms determining interaction between intracellular environment are largely unknown. Here, liquid chromatography-mass spectrometry metabolomics were used illuminate state reprogrammed harbor enhance tolerance. Timely accurate diagnosis as well efficient chemotherapies crucial preventing poor visual outcomes OTB patients. Unfortunately, efficacy current methods highly limited. Thus, results will propose novel therapeutic option synthetically kill modulating phenotypic laying foundation new, innovative regimen treating OTB. IMPORTANCE Understanding altered with mycobacterial dormancy identify new cure tuberculosis. The present study showed cellular metabolism foster enter into drug-tolerant state, thereby blunting anti-tuberculosis chemotherapy. serve protect treatment. LC-MS after co-treatment H 2 O enriched greater level oxidative stress. be restored manipulation strategy such most downstream glycolysis metabolite, phosphoenolpyruvate.