Mycobacterium tuberculosis transcriptome in intraocular tuberculosis

Abstract

Introduction. Intraocular tuberculosis (IOTB) is a significant cause of visual morbidity in tuberculosis (TB)-endemic countries. Although Mycobacterium tuberculosis (M. tb) has been detected in both the retinal pigment epithelial (RPE) cells and in the intraocular fluid (IOF) in some cases, IOTB is paucibacillary in the vast majority of patients. As a result, M. tb pathogenesis in the ocular compartment is poorly defined.Hypothesis. The transcriptional profile of M. tb in the ocular compartment will differ from those of M. tb in environments that represent earlier stages of infection.Aim. Our aim is to shed light on the pathogenesis of M. tb in a clinically relevant but challenging environment to study.Methodology. Whole-genome microarray analysis was performed on M. tb grown in an IOF model (artificial IOF; AIOF) over 6 days against reference log phase bacteria grown in 7H9. Results were compared to published M. tb transcriptomes in other physiologically relevant environments, e.g. RPE cell line.Results. M. tb replicates slowly in AIOF. Genes involved in active replication and aerobic respiration as well as lipid metabolism were either downregulated or not differentially expressed. Yet, M. tb in AIOF downregulated genes of the DosR regulon, indicating the suppression of dormancy, similar to M. tb in RPE cells. This transcriptional profile is distinct from the active and virulent transcriptomes of M. tb in alveolar epithelial cells and blood.Conclusion. M. tb likely acquires a non-invasive and quiescent phenotype, between active infection and dormancy, upon reaching an extrapulmonary niche, i.e. the ocular environment.

Keywords: Extrapulmonary tuberculosis; Mycobacterium tuberculosis; artificial intraocular fluid; dormancy; intraocular tuberculosis; quiescence.