PepN is a non-essential, cell wall-localized protein that contributes to neutrophil elastase-mediated killing of Streptococcus pneumoniae

Streptococcus pneumoniae (Spn) is an asymptomatic colonizer of the human nasopharynx but can also cause disease in the inner ear, meninges, lung and blood. Although various mechanisms contribute to the effective clearance of Spn, opsonophagocytosis by neutrophils is perhaps most critical. Upon phago...

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Bibliographic Details
Published in:PloS one 2019-02, Vol.14 (2), p.e0211632-e0211632
Main Authors: Nganje, Charmaine N, Haynes, Scott A, Qabar, Christine M, Lent, Rachel C, Bou Ghanem, Elsa N, Shainheit, Mara G
Format: Article
Language:English
Subjects:
Aminopeptidase
Aminopeptidases
Aminopeptidases - metabolism
Aminopeptidases - physiology
Bacterial proteins
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacterial Proteins - physiology
Biology and Life Sciences
CD13 Antigens - metabolism
Cell Wall - metabolism
Cell walls
Degradation
E coli
Elastase
Enzymes
Experiments
Gene expression
Genetic aspects
Healthy Volunteers
Humans
Inner ear
Leukocyte Elastase - metabolism
Leukocytes (neutrophilic)
Localization
Lung - metabolism
Lungs
Medicine and Health Sciences
Meninges
Nasopharynx
Neutrophils
Neutrophils - metabolism
Opsonophagocytosis
Pathogens
Peptides
Phagocytosis
Phenotypes
Pneumonia
Proteases
Proteins
Research and Analysis Methods
Serine
Serine Proteases - metabolism
Streptococcus infections
Streptococcus pneumoniae
Streptococcus pneumoniae - metabolism
Streptococcus pneumoniae - pathogenicity
Substrates
Young Adult
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Summary:Streptococcus pneumoniae (Spn) is an asymptomatic colonizer of the human nasopharynx but can also cause disease in the inner ear, meninges, lung and blood. Although various mechanisms contribute to the effective clearance of Spn, opsonophagocytosis by neutrophils is perhaps most critical. Upon phagocytosis, Spn is exposed to various degradative molecules, including a family of neutrophil serine proteases (NSPs) that are stored within intracellular granules. Despite the critical importance of NSPs in killing Spn, the bacterial proteins that are degraded by NSPs leading to Spn death are still unknown. In this report, we identify a 90kDa protein in a purified cell wall (CW) preparation, aminopeptidase N (PepN) that is degraded by the NSP neutrophil elastase (NE). Since PepN lacked a canonical signal sequence or LPxTG motif, we created a mutant expressing a FLAG tagged version of the protein and confirmed its localization to the CW compartment. We determined that not only is PepN a CW-localized protein, but also is a substrate of NE in the context of intact Spn cells. Furthermore, in comparison to wild-type TIGR4 Spn, a mutant strain lacking PepN demonstrated a significant hyper-resistance phenotype in vitro in the presence of purified NE as well as in opsonophagocytic assays with purified human neutrophils ex vivo. Taken together, this is the first study to demonstrate that PepN is a CW-localized protein and a substrate of NE that contributes to the effective killing of Spn by NSPs and human neutrophils.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0211632