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Candida albicans Inhibits Pseudomonas aeruginosa Virulence through Suppression of Pyochelin and Pyoverdine Biosynthesis.

Lopez-Medina E, Fan D, Coughlin LA, Ho EX, Lamont IL, Reimmann C, Hooper LV, Koh AY - PLoS Pathog. (2015)

Bottom Line: Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes.Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine.Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

ABSTRACT
Bacterial-fungal interactions have important physiologic and medical ramifications, but the mechanisms of these interactions are poorly understood. The gut is host to trillions of microorganisms, and bacterial-fungal interactions are likely to be important. Using a neutropenic mouse model of microbial gastrointestinal colonization and dissemination, we show that the fungus Candida albicans inhibits the virulence of the bacterium Pseudomonas aeruginosa by inhibiting P. aeruginosa pyochelin and pyoverdine gene expression, which plays a critical role in iron acquisition and virulence. Accordingly, deletion of both P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence. Heat-killed C. albicans has no effect on P. aeruginosa, whereas C. albicans secreted proteins directly suppress P. aeruginosa pyoverdine and pyochelin expression and inhibit P. aeruginosa virulence in mice. Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes. Finally, oral iron supplementation restores P. aeruginosa virulence in P. aeruginosa and C. albicans colonized mice. Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine. Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization. These findings validate the use of a mammalian model system to explore the complexities of polymicrobial, polykingdom infections in order to identify new therapeutic targets for preventing microbial disease.

No MeSH data available.


Related in: MedlinePlus

Deletion of P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence.A) GI colonization levels of wild type P. aeruginosa PAO1(circles); pyochelin deletional mutants (squares; ΔfptA, ΔpchE, ΔpchBA); pyoverdine deletional mutants (triangles; ΔpvdF, ΔpvdH, ΔpvdS); and pyochelin/pyoverdine deletional mutants (diamonds; ΔpchBAΔpvdF, ΔpchBAΔpvdS, ΔpchBAΔpvdH) in C3H/HeN mice. n = 8 mice per group. Points represent results from individual animals. Horizontal lines with bars represent the median with interquartile range. Statistical analysis performed by Mann-Whitney test. * p< 0.05; ** p<0.01; ns, not significant. B, C, D) Survival curves of antibiotic-treated neutropenic C3H/HeN mice GI colonized with B) PAO1 pyochelin deletional mutants, C) PAO1 pyoverdine deletional mutants, and D) PAO1 pyochelin/pyoverdine deletional mutants. n = 8 mice per group. Statistical analysis performed by log-rank test. * p< 0.05; ** p<0.01; ns, not significant.
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ppat.1005129.g003: Deletion of P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence.A) GI colonization levels of wild type P. aeruginosa PAO1(circles); pyochelin deletional mutants (squares; ΔfptA, ΔpchE, ΔpchBA); pyoverdine deletional mutants (triangles; ΔpvdF, ΔpvdH, ΔpvdS); and pyochelin/pyoverdine deletional mutants (diamonds; ΔpchBAΔpvdF, ΔpchBAΔpvdS, ΔpchBAΔpvdH) in C3H/HeN mice. n = 8 mice per group. Points represent results from individual animals. Horizontal lines with bars represent the median with interquartile range. Statistical analysis performed by Mann-Whitney test. * p< 0.05; ** p<0.01; ns, not significant. B, C, D) Survival curves of antibiotic-treated neutropenic C3H/HeN mice GI colonized with B) PAO1 pyochelin deletional mutants, C) PAO1 pyoverdine deletional mutants, and D) PAO1 pyochelin/pyoverdine deletional mutants. n = 8 mice per group. Statistical analysis performed by log-rank test. * p< 0.05; ** p<0.01; ns, not significant.

Mentions: In order to assess the relative importance of specific pyochelin and/or pyoverdine genes for P. aeruginosa GI colonization or virulence, we constructed P. aeruginosa pyochelin, pyoverdine, and pyochelin/pyoverdine deletional mutants. Since iron is essential for microbial growth and survival, the deletion of pyochelin/pyoverdine genes might significantly limit P. aeruginosa iron acquisition and thus inhibit P. aeruginosa growth and GI colonization. Interestingly, deleting either pyochelin or pyoverdine genes, or both pyochelin and pyoverdine genes, did not affect P. aeruginosa GI colonization (Fig 3A).


Candida albicans Inhibits Pseudomonas aeruginosa Virulence through Suppression of Pyochelin and Pyoverdine Biosynthesis.

Lopez-Medina E, Fan D, Coughlin LA, Ho EX, Lamont IL, Reimmann C, Hooper LV, Koh AY - PLoS Pathog. (2015)

Deletion of P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence.A) GI colonization levels of wild type P. aeruginosa PAO1(circles); pyochelin deletional mutants (squares; ΔfptA, ΔpchE, ΔpchBA); pyoverdine deletional mutants (triangles; ΔpvdF, ΔpvdH, ΔpvdS); and pyochelin/pyoverdine deletional mutants (diamonds; ΔpchBAΔpvdF, ΔpchBAΔpvdS, ΔpchBAΔpvdH) in C3H/HeN mice. n = 8 mice per group. Points represent results from individual animals. Horizontal lines with bars represent the median with interquartile range. Statistical analysis performed by Mann-Whitney test. * p< 0.05; ** p<0.01; ns, not significant. B, C, D) Survival curves of antibiotic-treated neutropenic C3H/HeN mice GI colonized with B) PAO1 pyochelin deletional mutants, C) PAO1 pyoverdine deletional mutants, and D) PAO1 pyochelin/pyoverdine deletional mutants. n = 8 mice per group. Statistical analysis performed by log-rank test. * p< 0.05; ** p<0.01; ns, not significant.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4552174&req=5

ppat.1005129.g003: Deletion of P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence.A) GI colonization levels of wild type P. aeruginosa PAO1(circles); pyochelin deletional mutants (squares; ΔfptA, ΔpchE, ΔpchBA); pyoverdine deletional mutants (triangles; ΔpvdF, ΔpvdH, ΔpvdS); and pyochelin/pyoverdine deletional mutants (diamonds; ΔpchBAΔpvdF, ΔpchBAΔpvdS, ΔpchBAΔpvdH) in C3H/HeN mice. n = 8 mice per group. Points represent results from individual animals. Horizontal lines with bars represent the median with interquartile range. Statistical analysis performed by Mann-Whitney test. * p< 0.05; ** p<0.01; ns, not significant. B, C, D) Survival curves of antibiotic-treated neutropenic C3H/HeN mice GI colonized with B) PAO1 pyochelin deletional mutants, C) PAO1 pyoverdine deletional mutants, and D) PAO1 pyochelin/pyoverdine deletional mutants. n = 8 mice per group. Statistical analysis performed by log-rank test. * p< 0.05; ** p<0.01; ns, not significant.
Mentions: In order to assess the relative importance of specific pyochelin and/or pyoverdine genes for P. aeruginosa GI colonization or virulence, we constructed P. aeruginosa pyochelin, pyoverdine, and pyochelin/pyoverdine deletional mutants. Since iron is essential for microbial growth and survival, the deletion of pyochelin/pyoverdine genes might significantly limit P. aeruginosa iron acquisition and thus inhibit P. aeruginosa growth and GI colonization. Interestingly, deleting either pyochelin or pyoverdine genes, or both pyochelin and pyoverdine genes, did not affect P. aeruginosa GI colonization (Fig 3A).

Bottom Line: Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes.Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine.Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

ABSTRACT
Bacterial-fungal interactions have important physiologic and medical ramifications, but the mechanisms of these interactions are poorly understood. The gut is host to trillions of microorganisms, and bacterial-fungal interactions are likely to be important. Using a neutropenic mouse model of microbial gastrointestinal colonization and dissemination, we show that the fungus Candida albicans inhibits the virulence of the bacterium Pseudomonas aeruginosa by inhibiting P. aeruginosa pyochelin and pyoverdine gene expression, which plays a critical role in iron acquisition and virulence. Accordingly, deletion of both P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence. Heat-killed C. albicans has no effect on P. aeruginosa, whereas C. albicans secreted proteins directly suppress P. aeruginosa pyoverdine and pyochelin expression and inhibit P. aeruginosa virulence in mice. Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes. Finally, oral iron supplementation restores P. aeruginosa virulence in P. aeruginosa and C. albicans colonized mice. Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine. Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization. These findings validate the use of a mammalian model system to explore the complexities of polymicrobial, polykingdom infections in order to identify new therapeutic targets for preventing microbial disease.

No MeSH data available.


Related in: MedlinePlus