Evaluating the role of Burkholderia pseudomallei K96243 toxins BPSS0390, BPSS0395, and BPSS1584 in persistent infection.
Burkholderia
antibiotic resistance
chronic infection
persistence
toxin-antitoxin
Journal
Cellular microbiology
ISSN: 1462-5822
Titre abrégé: Cell Microbiol
Pays: India
ID NLM: 100883691
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
20
02
2019
revised:
07
08
2019
accepted:
08
08
2019
pubmed:
11
8
2019
medline:
18
9
2020
entrez:
11
8
2019
Statut:
ppublish
Résumé
Burkholderia pseudomallei is the causative agent of melioidosis, a disease with a mortality rate of up to 40% even with treatment. Despite the ability of certain antibiotics to control initial infection, relapse occurs in treated patients. The inability of antibiotics to clear this bacterial infection is in part due to persistence, an evasion mechanism against antibiotics and the effect of host defenses. Evaluation of antibiotic efficacy against B. pseudomallei revealed that up to 48% of in vitro grown populations can survive in a persister state. Toxin-antitoxin (TA) systems have been previously implicated in modulating bacterial persistence. We generated three isogenic TA mutants and found that loss of each toxin gene did not alter antibiotic persistence or macrophage survival. In response to macrophage-induced persistence, all three toxin mutants demonstrated increased intracellular susceptibility to levofloxacin which in part was due to the inability of the mutants to induce persistence after nitric oxide or nutrient starvation. In an inhalational model of murine melioidosis, both ΔBPSS0395 and ΔBPSS1584 strains were attenuated, and treatment with levofloxacin led to significant reduction in lung colonisation and reduced splenic colonisation by ΔBPSS0395. Based on our findings, these toxins deserve additional evaluation as putative therapeutic targets.
Substances chimiques
Anti-Bacterial Agents
0
Toxins, Biological
0
Levofloxacin
6GNT3Y5LMF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13096Subventions
Organisme : Defense Threat Reduction Agency
ID : HDTRA1-12-17-FRCWMD
Pays : International
Organisme : Defense Threat Reduction Agency
ID : HDTRA1-12-17-FRCWMD
Pays : International
Organisme : Biodefense T32 fellowship
Pays : International
Organisme : UTMB
Pays : International
Informations de copyright
© 2019 John Wiley & Sons Ltd.
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