scholarly journals In Vitro Characterization of the Microglial Inflammatory Response to Streptococcus suis, an Important Emerging Zoonotic Agent of Meningitis

2010 ◽  
Vol 78 (12) ◽  
pp. 5074-5085 ◽  
Author(s):  
María de la Cruz Domínguez-Punaro ◽  
Mariela Segura ◽  
Irazú Contreras ◽  
Claude Lachance ◽  
Mathieu Houde ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Wall ◽  
Protein Kinase ◽  
Inflammatory Response ◽  
Bacterial Cell ◽  
Bacterial Cell Wall ◽  
Microglial Cells ◽  
Deficient Mutant ◽  
Wild Type ◽  
The Brain

ABSTRACT Streptococcus suis is an important swine and human pathogen responsible for septicemia and meningitis. In vivo research in mice suggested that in the brain, microglia might be involved in activating the inflammatory response against S. suis. The aim of this study was to better understand the interactions between S. suis and microglia. Murine microglial cells were infected with a virulent wild-type strain of S. suis. Two isogenic mutants deficient at either capsular polysaccharide (CPS) or hemolysin production were also included. CPS contributed to S. suis resistance to phagocytosis and regulated the inflammatory response by hiding proinflammatory components from the bacterial cell wall, while the absence of hemolysin, a potential cytotoxic factor, did not have a major impact on S. suis interactions with microglia. Wild-type S. suis induced enhanced expression of Toll-like receptor 2 by microglial cells, as well as phophotyrosine, protein kinase C, and different mitogen-activated protein kinase signaling events. However, cells infected with the CPS-deficient mutant showed overall stronger and more sustained phosphorylation profiles. CPS also modulated inducible nitric oxide synthase expression and further nitric oxide production from S. suis-infected microglia. Finally, S. suis-induced NF-κB translocation was faster for cells stimulated with the CPS-deficient mutant, suggesting that bacterial cell wall components are potent inducers of NF-κB. These results contribute to increase the knowledge of mechanisms underlying S. suis inflammation in the brain and will be useful in designing more efficient anti-inflammatory strategies for meningitis.

Bacterial cell wall peptidoglycan reaches the brain in EAE and multiple sclerosis (MS)

2016 ◽  
Vol 22 (1) ◽  
pp. 15
Author(s):  
Jon D. Laman ◽  
Bart J.L. Eggen ◽  
Erik W.G.M. Boddeke ◽  
Bert A.’t Hart
Keyword(s):  
Multiple Sclerosis ◽  
Cell Wall ◽  
Bacterial Cell ◽  
Bacterial Cell Wall ◽  
Cell Wall Peptidoglycan ◽  
The Brain

scholarly journals MurA escape mutations uncouple peptidoglycan biosynthesis from PrkA signaling

2021 ◽  
Author(s):  
Sabrina Wamp ◽  
Patricia Rothe ◽  
Gudrun Holland ◽  
Sven Halbedel
Keyword(s):  
Cell Wall ◽  
Listeria Monocytogenes ◽  
Protein Kinase ◽  
Bacterial Cell ◽  
Bacterial Cell Wall ◽  
Escape Mutation ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Main Component ◽  
Biosynthesis Regulation

AbstractGram-positive bacteria are protected by a thick mesh of peptidoglycan (PG) completely engulfing their cells. This PG network is the main component of the bacterial cell wall, it provides rigidity and acts as foundation for the attachment of other surface molecules. Biosynthesis of PG consumes a high amount of cellular resources and therefore requires careful adjustments to environmental conditions.An important switch in the control of PG biosynthesis of Listeria monocytogenes, a Gram-positive pathogen with a high infection fatality rate, is the serine/threonine protein kinase PrkA. A key substrate of this kinase is the small cytosolic protein ReoM. We have shown previously that ReoM phosphorylation regulates PG formation through control of MurA stability. MurA catalyzes the first step in PG biosynthesis and the current model suggests that phosphorylated ReoM prevents MurA degradation by the ClpCP protease. In contrast, conditions leading to ReoM dephosphorylation stimulate MurA degradation. How ReoM controls degradation of MurA and potential other substrates is not understood. Also, the individual contribution of the ∼20 other known PrkA targets to PG biosynthesis regulation is unknown.We here present murA mutants which escape proteolytic degradation. The release of MurA from ClpCP-dependent proteolysis was able to constitutively activate PG biosynthesis and further enhances the intrinsic cephalosporin resistance of L. monocytogenes. This activation required the RodA3/PBP B3 transglycosylase/transpeptidase pair as additional effectors of the PrkA signaling route. One murA escape mutation not only fully rescued an otherwise non-viable prkA mutant during growth in batch culture and inside macrophages but also overcompensated cephalosporin hypersensitivity. Our data collectively indicate that the main purpose of PrkA-mediated signaling in L. monocytogenes is control of MurA stability during extra- and intracellular growth. These findings have important implications for the understanding of PG biosynthesis regulation and β-lactam resistance of L. monocytogenes and related Gram-positive bacteria.Author SummaryPeptidoglycan (PG) is the main component of the bacterial cell wall and many of the PG synthesizing enzymes are antibiotic targets. We previously have discovered a new signaling route controlling PG production in the human pathogen Listeria monocytogenes. This route also determines the intrinsic resistance of L. monocytogenes against cephalosporins, a group of β-lactam antibiotics. Signaling involves PrkA, a membrane-embedded protein kinase, that is activated during cell wall stress to phosphorylate its target ReoM. Depending on its phosphorylation, ReoM activates or inactivates PG production by controlling the proteolytic stability of MurA, which catalyzes the first step in PG biosynthesis. MurA degradation depends on the ClpCP protease and we here have isolated murA mutations that escape this degradation. Using these mutants, we could show that regulation of PG biosynthesis through control of MurA stability is the primary purpose of PrkA-mediated signaling in L. monocytogenes. Further experiments identified the transglycosylase RodA and the transpeptidase PBP B3 as additional effectors of PrkA signaling. Our results suggest that both proteins act together to translate the signals received by PrkA into intensification of PG biosynthesis. These findings shed new light on the regulation of PG biosynthesis in Gram-positive bacteria with intrinsic β-lactam resistance.

Role of bacterial cell wall proteinase in antihypertension

2002 ◽  
Vol 22 (1-2) ◽  
pp. 209-222 ◽  
Author(s):  
Bénédicte Flambard
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Bacterial Cell Wall
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