Peptidoglycan Hydrolases RipA and Ami1 Are Critical for Replication and Persistence of Mycobacterium tuberculosis in the Host

MBio
Claire HealySabine Ehrt

Abstract

Synthesis and cleavage of the cell wall polymer peptidoglycan (PG) are carefully orchestrated processes and are essential for the growth and survival of bacteria. Yet, the function and importance of many enzymes that act on PG in Mycobacterium tuberculosis remain to be elucidated. We demonstrate that the activity of the N-acetylmuramyl-l-alanine amidase Ami1 is dispensable for cell division in M. tuberculosisin vitro yet contributes to the bacterium's ability to persist during chronic infection in mice. Furthermore, the d,l-endopeptidase RipA, a predicted essential enzyme, is dispensable for the viability of M. tuberculosis but required for efficient cell division in vitro and in vivo. Depletion of RipA sensitizes M. tuberculosis to rifampin and to cell envelope-targeting antibiotics. Ami1 helps sustain residual cell division in cells lacking RipA, but the partial redundancy provided by Ami1 is not sufficient during infection, as depletion of RipA prevents M. tuberculosis from replicating in macrophages and leads to dramatic killing of the bacteria in mice. Notably, RipA is essential for persistence of M. tuberculosis in mice, suggesting that cell division is required during chronic mouse infection. Despite the multiplicity of ...Continue Reading

References

Oct 15, 1994·FEMS Microbiology Letters·V Jarlier, H Nikaido
Jan 7, 2004·Cellular Microbiology·Petros C KarakousisSusan E Dorman
Feb 3, 2005·Nucleic Acids Research·Sabine EhrtDirk Schnappinger
Jul 21, 2006·Journal of Bacteriology·Richa PriyadarshiniKevin D Young
Oct 9, 2007·Molecular Microbiology·Erik C HettEric J Rubin
Feb 3, 2009·Nature Medicine·Wendy P GillDavid R Sherman
Jan 26, 2012·Science Signaling·Christine L GeeTom Alber
Aug 22, 2012·Molecular Microbiology·Pradeep KumarClifton E Barry
Oct 17, 2012·Molecular Microbiology·Waldemar Vollmer
Jul 8, 2014·Nature Reviews. Microbiology·Karen J Kieser, Eric J Rubin
Dec 9, 2014·Microbiology Spectrum·Dirk Schnappinger, Sabine Ehrt
Feb 1, 2015·Methods in Molecular Biology·Jarukit E LongChristopher M Sassetti
Mar 18, 2015·Methods in Molecular Biology·Kenan C MurphyChristopher M Sassetti
Feb 1, 2014·Microbiology Spectrum·Dirk Schnappinger, Sabine Ehrt
Oct 9, 2015·PLoS Computational Biology·Michael A DeJesusThomas R Ioerger
Mar 16, 2016·Journal of Bacteriology·Daniel J Martinelli, Martin S Pavelka
Dec 21, 2017·MBio·Sónia CastanheiraFrancisco García-Del Portillo
Oct 4, 2018·Cell Reports·Obolbek TurapovGalina V Mukamolova

❮ Previous
Next ❯

Citations

Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Saradindu SahaSomdeb BoseDasgupta
Dec 18, 2020·Frontiers in Chemistry·Pedro F DalbertoLuiz A Basso
Feb 21, 2021·Current Opinion in Microbiology·Katherine A Abrahams, Gurdyal S Besra
Mar 13, 2021·Microbiology Resource Announcements·Elizabeth D AmarhGraham F Hatfull
Jun 5, 2021·RSC Medicinal Chemistry·Katherine A Abrahams, Gurdyal S Besra
Oct 15, 2020·MBio·Elizabeth A Mueller, Petra Anne Levin
Jul 20, 2021·Antimicrobial Agents and Chemotherapy·Loes van SchieNico Callewaert

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
restriction digest

Software Mentioned

HP Digital Dispenser Data Merge
TRANSIT Tn - seq
HP Digital Dispenser
TRANSIT

Related Concepts

Related Feeds

Bacterial Cell Wall Structure (ASM)

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.

Bacterial Cell Wall Structure

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.