The PE and PPE Family Proteins of Mycobacterium tuberculosis: What they Are Up To?

Pal, Ranjan; Nazar, Faiza; Mukhopadhyay, Sangita

doi:10.1007/978-981-32-9413-4_8

Cited by 3 publications

(7 citation statements)

References 149 publications

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“…PE and PPE protein families are proteins unique to mycobacteria and are suspected to have roles in the pathogenicity of the organism ( Sampson, 2011 ; Timms et al, 2015 ). These proteins are typically found at the cell surface, with conserved N-terminal and C-terminal domains that broadly categorize these proteins into subfamilies ( Pal et al, 2019 ). Some PE/PPE proteins have been shown to elicit B cell responses ( Sampson, 2011 ) and affect macrophage or dentritic cells function ( Brennan et al, 2001 ; Bansal et al, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

Genomic epidemiology of Mycobacterium avium subsp. paratuberculosis isolates from Canadian dairy herds provides evidence for multiple infection events

et al. 2023

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Mycobacterium avium subsp. paratuberculosis (MAP) is the pathogen responsible for paratuberculosis or Johne’s Disease (JD) in ruminants, which is responsible for substantial economic losses worldwide. MAP transmission primarily occurs through the fecal-oral route, and the introduction of an MAP infected animal into a herd is an important transmission route. In the current study, we characterized MAP isolates from 67 cows identified in 20 herds from the provinces of Quebec and Ontario, Canada. Whole genome sequencing (WGS) was performed and an average genome coverage (relative to K-10) of ∼14.9 fold was achieved. The total number of SNPs present in each isolate varied from 51 to 132 and differed significantly between herds. Isolates with the highest genetic variability were generally present in herds from Quebec. The isolates were broadly separated into two main clades and this distinction was not influenced by the province from which they originated. Analysis of 8 MIRU-VNTR loci and 11 SSR loci was performed on the 67 isolates from the 20 dairy herds and publicly available references, notably major genetic lineages and six isolates from the province of Newfoundland and Labrador. All 67 field isolates were phylogenetically classified as Type II (C-type) and according to MIRU-VNTR, the predominant type was INMV 2 (76.1%) among four distinct patterns. Multilocus SSR typing identified 49 distinct INMV SSR patterns. The discriminatory index of the multilocus SSR typing was 0.9846, which was much higher than MIRU-VNTR typing (0.3740). Although multilocus SSR analysis provides good discriminatory power, the resolution was not informative enough to determine inter-herd transmission. In select cases, SNP-based analysis was the only approach able to document disease transmission between herds, further validated by animal movement data. The presence of SNPs in several virulence genes, notably for PE, PPE, mce and mmpL, is expected to explain differential antigenic or pathogenetic host responses. SNP-based studies will provide insight into how MAP genetic variation may impact host-pathogen interactions. Our study highlights the informative power of WGS which is now recommended for epidemiological studies and to document mixed genotypes infections.

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Section: Resultsmentioning

confidence: 99%

Genomic epidemiology of Mycobacterium avium subsp. paratuberculosis isolates from Canadian dairy herds provides evidence for multiple infection events

et al. 2023

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“…PPE proteins are involved in many functions, including adhesion to and invasion of host cells, host immune response modulation, and host environment survival [ 31 ]. PPE proteins are also highly polymorphic, which makes it difficult for the immune system to recognize and respond effectively in cases of index infection [ 42 ]. Localized PPE proteins within the MTB cell wall are secreted directly into the host cell via the T7SS.…”

Section: Reviewmentioning

confidence: 99%

“…Localized PPE proteins within the MTB cell wall are secreted directly into the host cell via the T7SS. This allows PPE proteins to interact directly with host cells and modulate the immune response [ 42 ]. Once secreted to the cell surface, PPE proteins are anchored in the cell wall via the PPE domain, a highly conserved domain throughout all PPE proteins [ 43 ].…”

Section: Reviewmentioning

confidence: 99%

“…It anchors PPE proteins to the cell wall and mediates their interactions with host cells, thus enabling MTB to modulate and evade the host’s immune system. PPE proteins are classified into several groups based on different criteria [ 42 , 43 ]. They can be categorized based on their sequence, with PPE-PPW proteins involved in adhesion and invasion of host cells, PPE-MPTR proteins modulating the host immune response, and other PPE proteins whose functions are not yet fully understood [ 44 ].…”

Section: Reviewmentioning

confidence: 99%

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The Role of Proline-Proline-Glutamic Acid (PPE) Proteins in Mycobacterium tuberculosis Virulence: Mechanistic Insights and Therapeutic Implications

Ilesanmi,

Odeniran,

Tatsipie

et al. 2024

Cureus

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For decades, tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), has remained a global health challenge. Central to this issue are the proline-proline-glutamic acid (PPE) proteins, which play a pivotal role in the pathogenesis and persistence of MTB. This article explores the molecular mechanisms of PPE proteins and their roles in facilitating MTB’s evasion of the host’s immune system while enhancing virulence and transmission. Focusing on the structural and functional aspects of PPE proteins, this review provides a detailed analysis of antigenic variation, a crucial mechanism allowing MTB to elude immune detection. It also probes the genetic diversity of these PPE proteins and their complex interactions with host immunity, offering insights into the challenges they pose for therapeutic development. This review delves into the potential of targeting PPE proteins in novel therapeutic strategies, discussing the prospects of drug and vaccine development. The evidence reviewed in this article underscores the pressing need for innovative approaches to combat TB, especially in the face of increasing drug resistance. Ultimately, this review article highlights the untapped potential of PPE proteins in revolutionizing TB treatment, paving the way for breakthroughs in drug and vaccine development.

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“…ESX‐5 exports the PE (proline‐glutamic acid) and PPE (proline‐proline‐glutamic acid) families of proteins [34]. PE and PPE proteins are well known for their role in regulating mycobacterium physiology, as well as in the modulation of host immune responses and TB pathogenesis [35]. By contrast to ESX‐1, ESX‐3 and ESX‐5, the other secretion systems, comprising ESX‐2 and ESX‐4, are not well studied.…”

Section: Secretion Systems In M Tuberculosismentioning

confidence: 99%

Secretory proteins of Mycobacterium tuberculosis and their roles in modulation of host immune responses: focus on therapeutic targets

2022

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Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, is one of the most successful pathogens in human history. An extremely resilient cell wall and highly evolved and coordinated strategies for immune evasion have made it a very formidable pathogen. The secretory proteins of M. tuberculosis play a crucial role in its virulence and immune evasion. The secretory proteins are secreted through tightly regulated secretion systems and modulate the host immune responses through a plethora of strategies, including epigenetic reprogramming of infected cells, targeting antigen presentation, inhibition of phagosomal maturation, modulation of cytokine production, apoptosis and redox regulation, etc. Upon infection, the secretory proteins become localized into various cellular organelles, such as nucleus, cytoplasm, phagosomes and Golgi, bodies and hijack the host machineries through their wide gamut of functions, including kinase, phosphatase, methyl transferase activities and interaction with several host partners. In this review, we discuss the secretion systems, the functions of various secretory proteins of M. tuberculosis and their roles in modulating immune responses of the host. We also discuss the feasibility of their use as possible therapeutic targets. This information is likely to improve our understanding of the host–pathogen interaction and help in the design of effective anti‐tuberculosis therapeutics.

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The PE and PPE Family Proteins of Mycobacterium tuberculosis: What they Are Up To?

Cited by 3 publications

References 149 publications

Genomic epidemiology of Mycobacterium avium subsp. paratuberculosis isolates from Canadian dairy herds provides evidence for multiple infection events

Genomic epidemiology of Mycobacterium avium subsp. paratuberculosis isolates from Canadian dairy herds provides evidence for multiple infection events

The Role of Proline-Proline-Glutamic Acid (PPE) Proteins in Mycobacterium tuberculosis Virulence: Mechanistic Insights and Therapeutic Implications

Secretory proteins of Mycobacterium tuberculosis and their roles in modulation of host immune responses: focus on therapeutic targets

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