000056104 001__ 56104
000056104 005__ 20210121114528.0
000056104 0247_ $$2doi$$a10.1111/cmi.12466
000056104 0248_ $$2sideral$$a92716
000056104 037__ $$aART-2015-92716
000056104 041__ $$aeng
000056104 100__ $$aCano, V.
000056104 245__ $$aKlebsiella pneumoniae survives within macrophages by avoiding delivery to lysosomes
000056104 260__ $$c2015
000056104 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056104 5203_ $$aKlebsiella pneumoniae is an important cause of community-acquired and nosocomial pneumonia. Evidence indicates that Klebsiella might be able to persist intracellularly within a vacuolar compartment. This study was designed to investigate the interaction between Klebsiella and macrophages. Engulfment of K.pneumoniae was dependent on host cytoskeleton, cell plasma membrane lipid rafts and the activation of phosphoinositide 3-kinase (PI3K). Microscopy studies revealed that K.pneumoniae resides within a vacuolar compartment, the Klebsiella-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 K.pneumoniae triggers a programmed cell death in macrophages displaying features of apoptosis. Our efforts to identify the mechanism(s) whereby K.pneumoniae 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 Klebsiella intracellular survival if bacteria were not opsonized. Furthermore, the environment found by Klebsiella within the KCV triggered the down-regulation of the expression of cps. Altogether, this study proves evidence that K.pneumoniae survives killing by macrophages by manipulating phagosome maturation that may contribute to Klebsiella pathogenesis. Prevailing belief states that the human pathogens Klebsiella pneumoniae is an extracellular pathogen. However, in this work, we demonstrate that K. pneumoniae co-opts the maturation of the phagosome manipulating a PI3K-AKT-RAB14 signalling cascade. Here, we also demonstrate that by preventing the activation of this cascade, the macrophages eliminate intracellular Klebsiella.
000056104 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PS09-00130$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2009-07885$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2012-39841
000056104 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056104 590__ $$a4.46$$b2015
000056104 591__ $$aMICROBIOLOGY$$b21 / 123 = 0.171$$c2015$$dQ1$$eT1
000056104 591__ $$aCELL BIOLOGY$$b56 / 187 = 0.299$$c2015$$dQ2$$eT1
000056104 592__ $$a2.949$$b2015
000056104 593__ $$aImmunology$$c2015$$dQ1
000056104 593__ $$aVirology$$c2015$$dQ1
000056104 593__ $$aMicrobiology$$c2015$$dQ1
000056104 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/submittedVersion
000056104 700__ $$aMarch, C.
000056104 700__ $$aInsua, J.L.
000056104 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, N.$$uUniversidad de Zaragoza
000056104 700__ $$aLlobet, E.
000056104 700__ $$aMoranta, D.
000056104 700__ $$aRegueiro, V.
000056104 700__ $$aBrennan, G.P.
000056104 700__ $$aMillán-Lou, M.I.
000056104 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000056104 700__ $$aGarmendia, J.
000056104 700__ $$aBengoechea, J.A.
000056104 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología
000056104 773__ $$g17, 11 (2015), 1537-1560$$pCell. microbiol.$$tCELLULAR MICROBIOLOGY$$x1462-5814
000056104 8564_ $$s1637991$$uhttps://zaguan.unizar.es/record/56104/files/texto_completo.pdf$$yPreprint
000056104 8564_ $$s58297$$uhttps://zaguan.unizar.es/record/56104/files/texto_completo.jpg?subformat=icon$$xicon$$yPreprint
000056104 909CO $$ooai:zaguan.unizar.es:56104$$particulos$$pdriver
000056104 951__ $$a2021-01-21-11:08:02
000056104 980__ $$aARTICLE