The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells

The Journal of Cell Biology
Ian J GlomskiDaniel A Portnoy

Abstract

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. The pore-forming cholesterol-dependent cytolysin, listeriolysin O (LLO), mediates bacterial escape from vesicles and is approximately 10-fold more active at an acidic than neutral pH. By swapping dissimilar residues from a pH-insensitive orthologue, perfringolysin O (PFO), we identified leucine 461 as unique to pathogenic Listeria and responsible for the acidic pH optimum of LLO. Conversion of leucine 461 to the threonine present in PFO increased the hemolytic activity of LLO almost 10-fold at a neutral pH. L. monocytogenes synthesizing LLO L461T, expressed from its endogenous site on the bacterial chromosome, resulted in a 100-fold virulence defect in the mouse listeriosis model. These bacteria escaped from acidic phagosomes and initially grew normally in cells and spread cell to cell, but prematurely permeabilized the host membrane and killed the cell. These data show that the acidic pH optimum of LLO results from an adaptive mutation that acts to limit cytolytic activity to acidic vesicles and prevent damage in the host cytosol, a strategy also used by host cells to compartmentalize lysos...Continue Reading

References

Apr 1, 1992·Infection and Immunity·D A PortnoyP Cossart
Apr 1, 1988·The Journal of Experimental Medicine·D A PortnoyD J Hinrichs
Jan 1, 1986·Annual Review of Biochemistry·I MellmanA Helenius
Jan 1, 1994·Methods in Enzymology·S Jones, D A Portnoy
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·R A BrundageD A Portnoy
Apr 1, 1993·Molecular Microbiology·A CamilliD A Portnoy
Jan 1, 1996·Annual Review of Cell and Developmental Biology·L D HernandezJ M White
Oct 7, 1997·The Journal of Experimental Medicine·K E BeauregardJ A Swanson
Feb 21, 1998·Current Biology : CB·H Bayley
Jun 4, 1999·Trends in Microbiology·E V SokurenkoD E Dykhuizen
Jan 20, 2000·Infection and Immunity·M M GeddeD A Portnoy
Jun 30, 2000·Current Opinion in Cell Biology·P O Falnes, K Sandvig
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·I WalevS Bhakdi
May 24, 2001·Immunity·B T Edelson, E R Unanue

❮ Previous
Next ❯

Citations

Oct 23, 2013·Microbes and Infection·Olivier Disson, Marc Lecuit
Jan 26, 2013·Animal Health Research Reviews·Keith P Poulsen, Charles J Czuprynski
May 25, 2012·Molecular Pharmaceutics·Max KullbergThomas J Anchordoquy
Apr 24, 2010·Nature·David RibetPascale Cossart
Jan 17, 2008·Nature Reviews. Microbiology·Kevin Hybiske, Richard S Stephens
Apr 17, 2009·Nature Reviews. Microbiology·Katrina RayChristoph M Tang
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Andrea L RadtkeMary X O'Riordan
Nov 3, 2004·The Journal of Experimental Medicine·Luciana O Andrade, Norma W Andrews
Jul 8, 2009·Infection and Immunity·Robert I LehrerWuyuan Lu
Sep 26, 2012·Infection and Immunity·Ascel Samba-LouakaPascale Cossart
Aug 20, 2008·Infection and Immunity·Betsy Kleba, Richard S Stephens
Sep 24, 2005·Infection and Immunity·Rodney K Tweten
Dec 21, 2010·Journal of Bacteriology·Ryan RampersaudAdam J Ratner
Sep 6, 2006·Journal of Bacteriology·Iharilalao DubailAlain Charbit
Sep 11, 2003·Microbiology and Molecular Biology Reviews : MMBR·Paul D Cotter, Colin Hill
Dec 17, 2008·Future Microbiology·Sigrid D AuweterB Brett Finlay
Aug 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Zhengyu WeiHoward Goldfine
Aug 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Daniel W SchuerchRodney K Tweten
May 28, 2013·Clinical & Developmental Immunology·Andreas F-P Sonnen, Philipp Henneke
Sep 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Luisa W ChengDaniel A Portnoy
Oct 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Laurel L LenzDaniel A Portnoy

❮ Previous
Next ❯

Datasets Mentioned

BETA
U84782

Methods Mentioned

BETA
flow cytometry
PCR

Software Mentioned

MacVector
Imagequant
Genetics
SoftMax Pro

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.