Klebsiella pneumoniae survives within macrophages by avoiding delivery to lysosomes. (17th July 2015)

• Record Type: Journal Article
• Authors: Cano, Victoria; March, Catalina; Insua, Jose Luis; Aguiló, Nacho; Llobet, Enrique; Moranta, David; Regueiro, Verónica; Brennan, Gerard P.; Millán‐Lou, Maria Isabel; Martín, Carlos; Garmendia, Junkal; Bengoechea, José A.
• Is Part Of: Cellular microbiology. Volume 17:Number 11(2015:Nov.)
• Page Start: 1537
• Page End: 1560
• Publication Date: 2015-07-17
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12466
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>K</italic> <italic>lebsiella pneumoniae</italic> is an important cause of community‐acquired and nosocomial pneumonia. Evidence indicates that <italic>K</italic><italic>lebsiella</italic> might be able to persist intracellularly within a vacuolar compartment. This study was designed to investigate the interaction between <italic>K</italic><italic>lebsiella</italic> and macrophages. Engulfment of <italic>K</italic><italic>. pneumoniae</italic> was dependent on host cytoskeleton, cell plasma membrane lipid rafts and the activation of phosphoinositide 3‐kinase (PI3K). Microscopy studies revealed that <italic>K</italic><italic>. pneumoniae</italic> resides within a vacuolar compartment, the <italic>K</italic><italic>lebsiella</italic>‐containing vacuole (KCV), which traffics within vacuoles associated with the endocytic pathway. In contrast to UV‐killed bacteria, the majority of live bacteria did not co‐localize with markers of the lysosomal compartment. Our data suggest that <italic>K</italic><italic>. pneumoniae</italic> triggers a programmed cell death in macrophages displaying features of apoptosis. Our efforts to identify the mechanism(s) whereby <italic>K</italic><italic>. pneumoniae</italic> prevents the fusion of the lysosomes to the KCV uncovered the central role of the PI3K–Akt–Rab14 axis to control the phagosome maturation. Our data revealed that the capsule is dispensable for <italic>K</italic><italic>lebsiella</italic> intracellular survival if bacteria were not opsonized. Furthermore, the environment found by <italic>K</italic><italic>lebsiella</italic> within the KCV triggered the down‐regulation of the expression of <italic>cps</italic>. Altogether, this study proves evidence that <italic>K</italic><italic>. pneumoniae</italic> survives killing by macrophages by manipulating phagosome maturation that may contribute to <italic>K</italic><italic>lebsiella</italic> pathogenesis.</p> </abstract>