NapM enhances the survival of Mycobacterium tuberculosis under stress and in macrophages

Communications Biology
Yu LiuZheng-Guo He

Abstract

Hostile environmental cues cause Mycobacterium tuberculosis to enter a state of slow growth for survival. However, the underlying regulatory mechanism remains unclear. DnaA is essential for DNA replication initiation and represents an efficient target for growth regulation in bacteria. Here, we show that the nucleoid-associated protein NapM is a DnaA antagonist, protecting M. tuberculosis from stress-mediated killing. NapM can be induced by diverse stressful signals. It binds to DnaA to inhibit both its DNA replication origin-binding and ATP hydrolysis activity. As a DnaA antagonist, NapM inhibits the mycobacterial DNA synthesis in vitro and in vivo in M. tuberculosis. Furthermore, we show that NapM contributes to the survival of M. tuberculosis under stress and within macrophages during infection. Our findings provide a previously unidentified mechanism of mycobacterial survival under stress and also suggest NapM as a potential drug target for tuberculosis control.

References

Sep 30, 2003·Nature Immunology·Suzanne M Hingley-WilsonWilliam R Jacobs
Mar 24, 2004·Nature Reviews. Microbiology·Graham R StewartDouglas B Young
Mar 24, 2006·Molecular Microbiology·Murty V V S MadirajuMalini Rajagopalan
Jun 7, 2006·Annual Review of Microbiology·Jon M Kaguni
Jun 17, 2006·Nature Reviews. Microbiology·Bruce R Levin, Daniel E Rozen
Dec 5, 2006·Nature Reviews. Microbiology·Kim Lewis
Apr 17, 2007·Nature Reviews. Microbiology·Melissa L Mott, James M Berger
Apr 27, 2007·FEMS Microbiology Reviews·Jolanta Zakrzewska-CzerwińskaWalter Messer
Jan 19, 2008·The FEBS Journal·Hua ZhangXian-En Zhang
Feb 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·R ColangeliD Alland
Aug 21, 2009·Nature Immunology·David G RussellFrédéric Altare
Nov 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Ganesh NatrajanLaurent Terradot
Feb 17, 2010·Nature Reviews. Microbiology·Tsutomu KatayamaKazuyuki Fujimitsu
Jun 10, 2010·Annual Review of Microbiology·Kim Lewis
Feb 11, 2012·FEMS Microbiology Reviews·Martin Gengenbacher, Stefan H E Kaufmann
Oct 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Myoungsun SonBetty Diamond
Mar 19, 2014·Current Opinion in Microbiology·Kristina Jonas
Apr 29, 2014·Cell·Etienne Maisonneuve, Kenn Gerdes
Dec 20, 2014·Cell·C J CambierLalita Ramakrishnan
Jul 25, 2015·Molecular Microbiology·Gorla PurushothamMurty V Madiraju
Nov 28, 2017·PLoS Genetics·Katherine M MannChristina L Stallings

❮ Previous
Next ❯

Citations

May 22, 2020·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Trisha ParbhooJacoba M Mouton
May 7, 2020·Frontiers in Microbiology·Joanna Hołówka, Jolanta Zakrzewska-Czerwińska

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
two-hybrid
chip
surface plasmon resonance
co-immunoprecipitation
Co-IP
electrophoretic mobility shift
electrophoretic mobility shift assay
flow cytometry
electrophoresis

Software Mentioned

Image Quant
MODEL
BIA evaluation
SWISS

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.