Abstract
The role of the unique proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood. One of the PE family proteins, PE11 (LipX or Rv1169c), specific to pathogenic mycobacteria is found to be over-expressed during infection of macrophages and in active TB patients. In this study, we report that M. smegmatis expressing PE11 (Msmeg-PE11) exhibited altered colony morphology and cell wall lipid composition leading to a marked increase in resistance against various environmental stressors and antibiotics. The cell envelope of Msmeg-PE11 also had greater amount of glycolipids and polar lipids. Msmeg-PE11 was found to have better survival rate in infected macrophages. Mice infected with Msmeg-PE11 had higher bacterial load, showed exacerbated organ pathology and mortality. The liver and lung of Msmeg-PE11-infected mice also had higher levels of IL-10, IL-4 and TNF-α cytokines, indicating a potential role of this protein in mycobacterial virulence.
Highlights
The role of the unique proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood
To understand how PE11 influence mycobacterial pathophysiology, we expressed pe[11] gene in a non-pathogenic M. smegmatis strain mc2155 (Msmeg-PE11), which is widely used as a surrogate bacterium to characterize M. tuberculosis protein[24]
We attempted to understand the possible role played by a Lip family protein of M. tuberculosis, PE11 which is a member of the unique PE/PPE family proteins, in mycobacterial pathophysiology and virulence
Summary
The role of the unique proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood. Mycobacterium tuberculosis, the causative agent for tuberculosis (TB) employs several strategies to modulate the host immune responses to favor its intracellular survival[1] It possesses a unique proline-glutamic acid (PE)/ proline-proline-glutamic acid (PPE) family of proteins whose role in the pathophysiology and virulence is not clearly understood[2]. Lipases/esterases and phospholipases are molecules that provide metabolic turnover of lipids and can be defined as essential biocatalysts for the hydrolysis of esters containing long-chain and short-chain fatty acids These fatty acids, on one side provide energy for intracellular persistence of the dormant bacilli and its reactivation and on the other side they can act as precursors for the cell wall lipids and are thought to contribute to virulence and pathogenicity of the bacilli[13]. The data presented indicate that PE11 probably plays an important role in M. tuberculosis virulence and establishment of a successful infection
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