Role of dipA and pilD in Francisella tularensis Susceptibility to Resazurin

Role of dipA and pilD in Francisella tularensis Susceptibility to Resazurin

The phenoxazine dye resazurin exhibits bactericidal activity against the Gram-negative pathogens Francisella tularensis and Neisseria gonorrhoeae. One resazurin derivative, resorufin pentyl ether, significantly reduces vaginal colonization by Neisseria gonorrhoeae in a mouse model of infection. The...

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Bibliographic Details
Published in:Antibiotics (Basel) Vol. 10; no. 8; p. 992
Main Authors: Souder, Kendall, Beatty, Emma J., McGovern, Siena C., Whaby, Michael, Young, Emily, Pancake, Jacob, Weekley, Daron, Rice, Justin, Primerano, Donald A., Denvir, James, Horzempa, Joseph, Schmitt, Deanna M.
Format: Journal Article
Language:English
Published: Basel MDPI AG 17-08-2021
MDPI
Subjects:
Antibiotics
antimicrobial
Antimicrobial agents
Bacteria
Bacterial infections
Bactericidal activity
Colonization
Complementation
Deletion mutant
DipA
Drug resistance
Francisella tularensis
Gene sequencing
Genes
Genomes
Mode of action
Mutation
Neisseria gonorrhoeae
Pathogens
Phenotypes
PilD
Proteins
resazurin
Resistant mutant
Resorufin
Staphylococcus infections
Susceptibility
Target recognition
tularemia
Vaccines
Vagina
Whole genome sequencing
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Summary:The phenoxazine dye resazurin exhibits bactericidal activity against the Gram-negative pathogens Francisella tularensis and Neisseria gonorrhoeae. One resazurin derivative, resorufin pentyl ether, significantly reduces vaginal colonization by Neisseria gonorrhoeae in a mouse model of infection. The narrow spectrum of bacteria susceptible to resazurin and its derivatives suggests these compounds have a novel mode of action. To identify potential targets of resazurin and mechanisms of resistance, we isolated mutants of F. tularensis subsp. holarctica live vaccine strain (LVS) exhibiting reduced susceptibility to resazurin and performed whole genome sequencing. The genes pilD (FTL_0959) and dipA (FTL_1306) were mutated in half of the 46 resazurin-resistant (RZR) strains sequenced. Complementation of select RZR LVS isolates with wild-type dipA or pilD partially restored sensitivity to resazurin. To further characterize the role of dipA and pilD in resazurin susceptibility, a dipA deletion mutant, ΔdipA, and pilD disruption mutant, FTL_0959d, were generated. Both mutants were less sensitive to killing by resazurin compared to wild-type LVS with phenotypes similar to the spontaneous resazurin-resistant mutants. This study identified a novel role for two genes dipA and pilD in F. tularensis susceptibility to resazurin.
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ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics10080992