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Cell Microbiol. 2017 Mar;19(3). doi: 10.1111/cmi.12662. Epub 2016 Nov 3.

Two lytic transglycosylases in Neisseria gonorrhoeae impart resistance to killing by lysozyme and human neutrophils.

Author information

1
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, 22908, USA.
2
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.

Abstract

Symptomatic infection by Neisseria gonorrhoeae (Gc) produces a potent inflammatory response, resulting in a neutrophil-rich exudate. A population of Gc can survive the killing activities of neutrophils for reasons not completely understood. Unlike other Gram-negative bacteria, Gc releases monomeric peptidoglycan (PG) extracellularly, dependent on two nonessential, nonredundant lytic transglycosylases (LTs), LtgA and LtgD. PG released by LtgA and LtgD can stimulate host immune responses. We report that ΔltgAΔltgD Gc were decreased in survival in the presence of primary human neutrophils but otherwise grew equally to wild-type Gc. Adding PG monomer failed to alter ΔltgAΔltgD Gc survival. Thus, LTs protect Gc from neutrophils independently of monomer release. We found two reasons to explain decreased survival of the double LT mutant. First, ΔltgAΔltgD Gc was more sensitive to the neutrophil antimicrobial proteins lysozyme and neutrophil elastase, but not others. Sensitivity to lysozyme correlated with decreased Gc envelope integrity. Second, exposure of neutrophils to ΔltgAΔltgD Gc increased the release of neutrophil granule contents extracellularly and into Gc phagosomes. We conclude that LtgA and LtgD protect Gc from neutrophils by contributing to envelope integrity and limiting bacterial exposure to select granule-localized antimicrobial proteins. These observations are the first to link bacterial degradation by lysozyme to increased neutrophil activation.

PMID:
27597434
PMCID:
PMC5303151
DOI:
10.1111/cmi.12662
[Indexed for MEDLINE]
Free PMC Article

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