THE ROLE OF OPSONINS IN PHAGOCYTOSIS AND INTRACELLULAR KILLING OF GRAM-NEGATIVE BACTERIA BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES (PMN)

AbstractBoth Toll-like receptor 4 (TLR4)– and MD-2–deficient mice succumb to otherwise nonfatal Gram-negative bacteria inocula, demonstrating the pivotal role played by these proteins in antibacterial defense in mammals. MD-2 is a soluble endogenous ligand for TLR4 and a receptor for lipopolysaccharide (LPS). LPS-bound MD-2 transmits an activating signal onto TLR4. In this report, we show that both recombinant and endogenous soluble MD-2 bind tightly to the surface of live Gram-negative bacteria. As a consequence, MD-2 enhances cellular activation, bacterial internalization, and intracellular killing, all in a TLR4-dependent manner. The enhanced internalization of MD-2–coated bacteria was not observed in macrophages expressing Lpsd, a signaling-incompetent mutant form of TLR4, suggesting that the enhanced phagocytosis observed is dependent on signal transduction. The data confirm the notion that soluble MD-2 is a genuine opsonin that enhances proinflammatory opsonophagocytosis by bridging live Gram-negative bacteria to the LPS transducing complex. The presented results extend our understanding of the role of the TLR4/MD-2 signaling axis in bacterial recognition by phagocytes.

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Effect of Sch 29482 on Gram-negative bacteria in broth, serum and in combination with human polymorphonuclear leukocytes

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/9.suppl_c.213 ◽

1982 ◽

Vol 9 (suppl C) ◽

pp. 213-219

Author(s):

F. D. Daschner ◽

H. Langmaack ◽

M. Bassler ◽

U. Wais

Keyword(s):

Polymorphonuclear Leukocytes ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Human Polymorphonuclear Leukocytes

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Killing of gram-negative bacteria by polymorphonuclear leukocytes: role of an O2-independent bactericidal system.

Journal of Clinical Investigation ◽

10.1172/jci110535 ◽

1982 ◽

Vol 69 (4) ◽

pp. 959-970 ◽

Cited By ~ 54

Author(s):

J Weiss ◽

M Victor ◽

O Stendhal ◽

P Elsbach

Keyword(s):

Polymorphonuclear Leukocytes ◽

Gram Negative Bacteria ◽

Gram Negative

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MexAB-OprM Efflux Pump Interaction with the Peptidoglycan of Escherichia coli and Pseudomonas aeruginosa

International Journal of Molecular Sciences ◽

10.3390/ijms22105328 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5328

Author(s):

Miao Ma ◽

Margaux Lustig ◽

Michèle Salem ◽

Dominique Mengin-Lecreulx ◽

Gilles Phan ◽

...

Keyword(s):

Escherichia Coli ◽

Pseudomonas Aeruginosa ◽

Cell Division ◽

Membrane Proteins ◽

Outer Membrane ◽

Efflux Pump ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Active Efflux

One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans.

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