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Updated: Jan 21, 2026

Electroporation of Mycobacteria
Published on: May 23, 2008
Protein Export into and across the Atypical Diderm Cell Envelope of Mycobacteria
Vincent J C van Winden1, Edith N G Houben2, Miriam Braunstein3
1Department of Medical Microbiology and Infection Control, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
Mycobacteria, including the infamous pathogen Mycobacterium tuberculosis, are high-GC Gram-positive bacteria with a distinctive cell envelope. Although there is a typical inner membrane, the mycobacterial cell envelope is unusual in having its peptidoglycan layer connected to a polymer of arabinogalactan, which in turn is covalently attached to long-chain mycolic acids that help form a highly impermeable mycobacterial outer membrane. This complex double-membrane, or diderm, cell envelope imparts mycobacteria with unique requirements for protein export into and across the cell envelope for secretion into the extracellular environment. In this article, we review the four protein export pathways known to exist in mycobacteria: two conserved systems that exist in all types of bacteria (the Sec and Tat pathways) and two specialized systems that exist in mycobacteria, corynebacteria, and a subset of low-GC Gram-positive bacteria (the SecA2 and type VII secretion pathways). We describe the progress made over the past 15 years in understanding each of these mycobacterial export pathways, and we highlight the need for research to understand the specific steps of protein export across the mycobacterial outer membrane.
Insights
Mycobacteria possess a unique double-membrane cell envelope requiring specialized protein export. This review covers conserved (Sec, Tat) and specialized (SecA2, type VII) secretion pathways, highlighting research needs for outer membrane transport.
Area of Science:
- Microbiology
- Cell Biology
- Bacterial Pathogenesis
Background:
- Mycobacteria feature a complex, high-GC Gram-positive cell envelope with an outer membrane.
- This unique structure necessitates specialized protein export mechanisms for extracellular secretion.
Purpose of the Study:
- To review the four known protein export pathways in mycobacteria.
- To summarize recent advancements in understanding these pathways over the past 15 years.
- To identify critical research gaps in mycobacterial protein export.
Main Methods:
- Literature review of protein export pathways in mycobacteria.
- Analysis of conserved (Sec, Tat) and specialized (SecA2, type VII) secretion systems.
- Synthesis of research progress and future directions.
Main Results:
- Four protein export pathways identified: Sec, Tat, SecA2, and type VII secretion.
- Significant progress in understanding SecA2 and type VII pathways in mycobacteria.
- Conserved Sec and Tat pathways also play roles in mycobacterial protein export.
Conclusions:
- Mycobacterial protein export relies on both conserved and specialized pathways.
- Further research is crucial to elucidate protein transport across the mycobacterial outer membrane.
- Understanding these pathways is key to targeting mycobacterial infections.
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