Heme inhibits the activity of a c-di-GMP phosphodiesterase in Vibrio cholerae

Heckler, Ilana; Hossain, S. M. Zakir; Boon, Elizabeth M.

doi:10.1016/j.bbrc.2020.06.048

Cited by 6 publications

(17 citation statements)

References 23 publications

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“…S6 B ). Specifically, the Soret band around 420 nm confirmed the presence of CdpA bound to ferrous (Fe II ) heme, and a broader Soret band, shifted to around 395 nm, indicated the presence of the Fe II -NO complex as previously described ( 27 ). In vitro PDE assays of these samples, however, showed that there was only a slight and inconsistent increase in PDE activity for Fe II -NO CdpA compared to Fe II -CdpA ( SI Appendix , Fig.…”

Section: Resultssupporting

confidence: 80%

“…S5 A ). CdpA is a functional PDE that contains a NosP sensory domain ( 26 , 27 ). Deleting cdpA in a clean background recapitulated the improved binding under sealed conditions that was originally selected for ( SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

“…CdpA encodes a NosP domain, which has recently been shown to bind heme in a manner that alters its PDE activity ( 27 ). NosP domains have previously been implicated in sensing NO ( 28 ), and bacterial NO production generally occurs under microaerobic conditions ( 29 , 30 ).…”

Section: Resultsmentioning

confidence: 99%

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Nitric oxide stimulates type IV MSHA pilus retraction in Vibrio cholerae via activation of the phosphodiesterase CdpA

Hughes

Floyd

Hossain

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Bacteria use surface appendages called type IV pili to perform diverse activities including DNA uptake, twitching motility, and attachment to surfaces. The dynamic extension and retraction of pili are often required for these activities, but the stimuli that regulate these dynamics remain poorly characterized. To address this question, we study the bacterial pathogen Vibrio cholerae, which uses mannose-sensitive hemagglutinin (MSHA) pili to attach to surfaces in aquatic environments as the first step in biofilm formation. Here, we use a combination of genetic and cell biological approaches to describe a regulatory pathway that allows V. cholerae to rapidly abort biofilm formation. Specifically, we show that V. cholerae cells retract MSHA pili and detach from a surface in a diffusion-limited, enclosed environment. This response is dependent on the phosphodiesterase CdpA, which decreases intracellular levels of cyclic-di-GMP to induce MSHA pilus retraction. CdpA contains a putative nitric oxide (NO)–sensing NosP domain, and we demonstrate that NO is necessary and sufficient to stimulate CdpA-dependent detachment. Thus, we hypothesize that the endogenous production of NO (or an NO-like molecule) in V. cholerae stimulates the retraction of MSHA pili. These results extend our understanding of how environmental cues can be integrated into the complex regulatory pathways that control pilus dynamic activity and attachment in bacterial species.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

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Nitric oxide stimulates type IV MSHA pilus retraction in Vibrio cholerae via activation of the phosphodiesterase CdpA

Hughes

Floyd

Hossain

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…S5A). CdpA is a functional PDE that contains a NosP sensory domain 24,25 . In a MixD assay, the ΔcdpA mutant exhibited significantly delayed detachment compared to the parental strain (Fig.…”

Section: Cell Detachment Requires the Phosphodiesterase Cdpamentioning

confidence: 99%

“…Other oxygen-responsive PDEs and DGCs have been characterized, often sensing oxygen through a hemebinding PAS or globin domain [26][27][28][29] . CdpA lacks these domains, and instead encodes a NosP domain, which has recently been shown to bind heme in a manner that alters its PDE activity 25 . NosP domains have previously been implicated in sensing NO 30 , and bacterial NO production generally occurs under microaerobic conditions 31,32 .…”

Section: Cell Detachment Requires the Phosphodiesterase Cdpamentioning

confidence: 99%

Oxygen depletion and nitric oxide stimulate type IV MSHA pilus retraction inVibrio choleraevia activation of the phosphodiesterase CdpA

Hughes

Floyd

Hossain

et al. 2021

Preprint

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Bacteria use surface appendages called type IV pili to perform diverse activities including DNA uptake, twitching motility, and attachment to surfaces. Dynamic extension and retraction of pili is often required for these activities, but the stimuli that regulate these dynamics remain poorly characterized. To study this question, we use the bacterial pathogen Vibrio cholerae, which uses mannose-sensitive hemagglutinin (MSHA) pili to attach to surfaces in aquatic environments as the first step in biofilm formation. Here, we find that V. cholerae cells retract MSHA pili and detach from a surface in microaerobic conditions. This response is dependent on the phosphodiesterase CdpA, which decreases intracellular levels of cyclic-di-GMP (c-di-GMP) under microaerobic conditions to induce MSHA pilus retraction. CdpA contains a putative NO-sensing NosP domain, and we demonstrate that nitric oxide (NO) is necessary and sufficient to stimulate CdpA-dependent detachment. Thus, we hypothesize that microaerobic conditions result in endogenous production of NO (or an NO-like molecule) in V. cholerae. Together, these results describe a regulatory pathway that allows V. cholerae to rapidly abort biofilm formation. More broadly, these results show how environmental cues can be integrated into the complex regulatory pathways that control pilus dynamic activity and attachment in bacterial species.

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NosP Detection of Heme Modulates Burkholderia thailandensis Biofilm Formation

Nisbett

Guo

et al. 2023

Biochemistry

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Aggregated bacteria embedded within self-secreted extracellular polymeric substances, or biofilms, are resistant to antibiotics and cause chronic infections. As such, they are a significant public health threat. Heme is an abundant iron source for pathogenic bacteria during infection; many bacteria have systems to detect heme assimilated from host cells, which is correlated with the transition between acute and chronic infection states. Here, we investigate the heme-sensing function of a newly discovered multifactorial sensory hemoprotein called NosP and its role in biofilm regulation in the soil-dwelling bacterium Burkholderia thailandensis, the close surrogate of Bio-Safety-Level-3 pathogen Burkholderia pseudomallei. The NosP family protein has previously been shown to exhibit both nitric oxide (NO)- and heme-sensing functions and to regulate biofilms through NosP-associated histidine kinases and two-component systems. Our in vitro studies suggest that BtNosP exhibits heme-binding kinetics and thermodynamics consistent with a labile heme-responsive protein and that the holo-form of BtNosP acts as an inhibitor of its associated histidine kinase BtNahK. Furthermore, our in vivo studies suggest that increasing the concentration of extracellular heme decreases B. thailandensis biofilm formation, and deletion of nosP and nahK abolishes this phenotype, consistent with a model that BtNosP detects heme and exerts an inhibitory effect on BtNahK to decrease the biofilm.

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Heme inhibits the activity of a c-di-GMP phosphodiesterase in Vibrio cholerae

Cited by 6 publications

References 23 publications

Nitric oxide stimulates type IV MSHA pilus retraction in Vibrio cholerae via activation of the phosphodiesterase CdpA

Nitric oxide stimulates type IV MSHA pilus retraction in Vibrio cholerae via activation of the phosphodiesterase CdpA

Oxygen depletion and nitric oxide stimulate type IV MSHA pilus retraction inVibrio choleraevia activation of the phosphodiesterase CdpA

NosP Detection of Heme Modulates Burkholderia thailandensis Biofilm Formation

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