scholarly journals Kinome Analysis of Host Response to Mycobacterial Infection: a Novel Technique in Proteomics

2003 ◽  
Vol 71 (10) ◽  
pp. 5514-5522 ◽  
Author(s):  
Anne Lise K. Hestvik ◽  
Zakaria Hmama ◽  
Yossef Av-Gay
Keyword(s):  
Cell Wall ◽  
Protein Kinase ◽  
Host Response ◽  
Glycogen Synthase ◽  
Mycobacterial Infection ◽  
Host Protein ◽  
Cell Wall Component ◽  
Downstream Target ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall

ABSTRACT An array of mammalian phospho-specific antibodies was used to screen for a host response upon mycobacterial infection, reflected as changes in host protein phosphorylation. Changes in the phosphorylation state of 31 known signaling molecules were tracked after infection with live or heat killed Mycobacterium bovis BCG or after incubation with the mycobacterial cell wall component lipoarabinomannan (LAM). Mycobacterial infection triggers a signaling cascade leading to activation of stress-activated protein kinase and its subsequent downstream target, c-Jun. Mycobacteria were also shown to inhibit the activation of protein kinase C ε and to induce phosphorylation of proteins not yet known to be involved in mycobacterial infection, such as the cytoskeletal protein α-adducin, glycogen synthase kinase 3β, and a receptor subunit involved in regulation of intracellular Ca2+ levels. The mycobacterial cell wall component LAM has been identified as a trigger for some of these modulation events.

Expression of a long pentraxin, PTX3, by monocytes exposed to the mycobacterial cell wall component lipoarabinomannan.

1997 ◽  
Vol 65 (4) ◽  
pp. 1345-1350 ◽  
Author(s):  
V Vouret-Craviari ◽  
C Matteucci ◽  
G Peri ◽  
G Poli ◽  
M Introna ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Wall Component ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall

Contrasting roles of the innate receptors TREM2 versus Mincle in the recognition and response of macrophages to mycolic acid-containing lipids in mycobacterial cell walls

2020 ◽  
Author(s):  
Ei'ichi Iizasa ◽  
Yasushi Chuma ◽  
Takayuki Uematsu ◽  
Mio Kubota ◽  
Hiroaki Kawaguchi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterial Infection ◽  
Mycolic Acid ◽  
Dependent Manner ◽  
Independent Manner ◽  
Lectin Receptors ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall

Abstract Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, their mechanism of action remains unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2. Macrophages responded to glycosylated MA-containing lipids in a Mincle/FcRγ/CARD9-dependent manner to produce inflammatory cytokines and recruit inducible nitric oxide synthase (iNOS)-positive mycobactericidal macrophages. Conversely, macrophages responded to non-glycosylated MAs in a TREM2/DAP12-dependent but CARD9-independent manner to recruit iNOS-negative mycobacterium-permissive macrophages. Furthermore, TREM2 deletion enhanced Mincle-induced macrophage activation in vitro and inflammation in vivo and accelerated the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts Mincle-FcRγ-CARD9-mediated anti-mycobacterial immunity. Mycobacteria, therefore, harness TREM2 for immune evasion.

Conserved Molecular Superlattices in a Series of Homologous Synthetic Mycobacterial Cell-Wall Lipids Forming Interdigitated Bilayers

Langmuir ◽  
2016 ◽  
Vol 32 (48) ◽  
pp. 12693-12701 ◽  
Author(s):  
Birte Martin-Bertelsen ◽  
Anan Yaghmur ◽  
Henrik Franzyk ◽  
Sarah Justesen ◽  
Jacob J. K. Kirkensgaard ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall

scholarly journals Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target

Parasitology ◽  
2016 ◽  
Vol 145 (2) ◽  
pp. 116-133 ◽  
Author(s):  
KATHERINE A. ABRAHAMS ◽  
GURDYAL S. BESRA
Keyword(s):  
Cell Wall ◽  
Drug Targets ◽  
Complex Structure ◽  
Supporting Cell ◽  
Chemotherapeutic Agents ◽  
World Health ◽  
Mycobacterial Cell ◽  
Clinical Drugs ◽  
Health Organization ◽  
Mycobacterial Cell Wall

SUMMARYMycobacterium tuberculosis(Mtb), the etiological agent of tuberculosis (TB), is recognized as a global health emergency as promoted by the World Health Organization. Over 1 million deathsperyear, along with the emergence of multi- and extensively-drug resistant strains ofMtb, have triggered intensive research into the pathogenicity and biochemistry of this microorganism, guiding the development of anti-TB chemotherapeutic agents. The essential mycobacterial cell wall, sharing some common features with all bacteria, represents an apparent ‘Achilles heel’ that has been targeted by TB chemotherapy since the advent of TB treatment. This complex structure composed of three distinct layers, peptidoglycan, arabinogalactan and mycolic acids, is vital in supporting cell growth, virulence and providing a barrier to antibiotics. The fundamental nature of cell wall synthesis and assembly has rendered the mycobacterial cell wall as the most widely exploited target of anti-TB drugs. This review provides an overview of the biosynthesis of the prominent cell wall components, highlighting the inhibitory mechanisms of existing clinical drugs and illustrating the potential of other unexploited enzymes as future drug targets.

scholarly journals Organization of the mycobacterial cell wall: a nanoscale view

2007 ◽  
Vol 456 (1) ◽  
pp. 117-125 ◽  
Author(s):  
David Alsteens ◽  
Claire Verbelen ◽  
Etienne Dague ◽  
Dominique Raze ◽  
Alain R. Baulard ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall
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