Impact of Type III Secretion Effectors and of Phenoxyacetamide Inhibitors of Type III Secretion on Abscess Formation in a Mouse Model of Pseudomonas aeruginosa Infection
is a leading cause of intra-abdominal infections, wound infections, and community-acquired folliculitis, each of which may involve macro- or microabscess formation. The rising incidence of multidrug resistance among isolates has increased both the economic burden and the morbidity and mortality asso...
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Published in | Antimicrobial agents and chemotherapy Vol. 61; no. 11 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Microbiology
01.11.2017
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Subjects | |
Online Access | Get full text |
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Summary: | is a leading cause of intra-abdominal infections, wound infections, and community-acquired folliculitis, each of which may involve macro- or microabscess formation. The rising incidence of multidrug resistance among
isolates has increased both the economic burden and the morbidity and mortality associated with
disease and necessitates a search for novel therapeutics. Previous work from our group detailed novel phenoxyacetamide inhibitors that block type III secretion and injection into host cells
In this study, we used a mouse model of
abscess formation to test the
efficacy of these compounds against the
type III secretion system (T3SS). Bacteria used the T3SS to intoxicate infiltrating neutrophils to establish abscesses. Despite this antagonism, sufficient numbers of functioning neutrophils remained for proper containment of the abscesses, as neutrophil depletion resulted in an increased abscess size, the formation of dermonecrotic lesions on the skin, and the dissemination of
to internal organs. Consistent with the specificity of the T3SS-neutrophil interaction,
bacteria lacking a functional T3SS were fully capable of causing abscesses in a neutropenic host. Phenoxyacetamide inhibitors attenuated abscess formation and aided in the immune clearance of the bacteria. Finally, a
strain resistant to the phenoxyacetamide compound was fully capable of causing abscess formation even in the presence of the T3SS inhibitors. Together, our results further define the role of type III secretion in murine abscess formation and demonstrate the
efficacy of phenoxyacetamide inhibitors in
infection. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Bryan J. Berube, Infectious Disease Research Institute, Seattle, Washington, USA. Citation Berube BJ, Murphy KR, Torhan MC, Bowlin NO, Williams JD, Bowlin TL, Moir DT, Hauser AR. 2017. Impact of type III secretion effectors and of phenoxyacetamide inhibitors of type III secretion on abscess formation in a mouse model of Pseudomonas aeruginosa infection. Antimicrob Agents Chemother 61:e01202-17. https://doi.org/10.1128/AAC.01202-17. |
ISSN: | 0066-4804 1098-6596 |
DOI: | 10.1128/AAC.01202-17 |