In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 1 ( 2023-1-25), p. e1011023-
Abstract:
Pseudomonas aeruginosa , an opportunistic Gram-negative pathogen, is a leading cause of bacteremia with a high mortality rate. We recently reported that P . aeruginosa forms a persister-like sub-population of evaders in human plasma. Here, using a gain-of-function transposon sequencing (Tn-seq) screen in plasma, we identified and validated previously unknown factors affecting bacterial persistence in plasma. Among them, we identified a small periplasmic protein, named SrgA, whose expression leads to up to a 100-fold increase in resistance to killing. Additionally, mutants in pur and bio genes displayed higher tolerance and persistence, respectively. Analysis of several steps of the complement cascade and exposure to an outer-membrane-impermeable drug, nisin, suggested that the mutants impede membrane attack complex (MAC) activity per se . Electron microscopy combined with energy-dispersive X-ray spectroscopy (EDX) revealed the formation of polyphosphate (polyP) granules upon incubation in plasma of different size in purD and wild-type strains, implying the bacterial response to a stress signal. Indeed, inactivation of ppk genes encoding polyP-generating enzymes lead to significant elimination of persisting bacteria from plasma. Through this study, we shed light on a complex P . aeruginosa response to the plasma conditions and discovered the multifactorial origin of bacterial resilience to MAC-induced killing.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011023
DOI:
10.1371/journal.ppat.1011023.g001
DOI:
10.1371/journal.ppat.1011023.g002
DOI:
10.1371/journal.ppat.1011023.g003
DOI:
10.1371/journal.ppat.1011023.g004
DOI:
10.1371/journal.ppat.1011023.g005
DOI:
10.1371/journal.ppat.1011023.g006
DOI:
10.1371/journal.ppat.1011023.g007
DOI:
10.1371/journal.ppat.1011023.g008
DOI:
10.1371/journal.ppat.1011023.t001
DOI:
10.1371/journal.ppat.1011023.s001
DOI:
10.1371/journal.ppat.1011023.s002
DOI:
10.1371/journal.ppat.1011023.s003
DOI:
10.1371/journal.ppat.1011023.s004
DOI:
10.1371/journal.ppat.1011023.s005
DOI:
10.1371/journal.ppat.1011023.s006
DOI:
10.1371/journal.ppat.1011023.s007
DOI:
10.1371/journal.ppat.1011023.s008
DOI:
10.1371/journal.ppat.1011023.s009
DOI:
10.1371/journal.ppat.1011023.s010
DOI:
10.1371/journal.ppat.1011023.r001
DOI:
10.1371/journal.ppat.1011023.r002
DOI:
10.1371/journal.ppat.1011023.r003
DOI:
10.1371/journal.ppat.1011023.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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