Recent Evidence for Multifactorial Biofilm Regulation by Heme Sensor Proteins NosP and H-NOX

Fu, Jiayuan; Hall, Steven C.; Boon, Elizabeth M.

doi:10.1246/cl.200945

Cited by 5 publications

(5 citation statements)

References 94 publications

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“…Static Biofilm Assay. Ability of wild-type and ∆nahK to form biofilm under aerobic and anaerobic conditions was assessed using a modified microtiter dish assay in 6-well plates to quantify surfaced attached bacteria grown statically (46). To assess biofilm formation aerobically, 5mL day cultures were prepared from overnight cultures and grown until the cultures reached an OD 600 of 1.0.…”

Section: Methodsmentioning

confidence: 99%

The Histidine Kinase NahK Regulates Denitrification and Nitric Oxide Accumulation through RsmA inPseudomonas aeruginosa

Guercio,

Boon

2024

Preprint

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Pseudomonas aeruginosahave a versatile metabolism; they can adapt to many stressors, including limited oxygen and nutrient availability. This versatility is especially important within a biofilm where multiple microenvironments are present. As a facultative anaerobe,P. aeruginosacan survive under anaerobic conditions utilizing denitrification. This process produces nitric oxide (NO) which has been shown to result in cell elongation. However, the molecular mechanism underlying this phenotype is poorly understood. Our laboratory has previously shown that NosP is a NO-sensitive hemoprotein that works with the histidine kinase NahK to regulate biofilm inP. aeruginosa. In this study, we identify NahK as a novel regulator of denitrification under anaerobic conditions. Under anaerobic conditions, deletion ofnahKleads to a reduction of growth coupled with reduced transcriptional expression and activity of the denitrification reductases. Further, during stationary phase under anaerobic conditions, ΔnahKdoes not exhibit cell elongation, which is characteristic ofP. aeruginosa. We determine the loss of cell elongation is due to changes in NO accumulation inΔnahK. We further provide evidence that NahK may regulate denitrification through modification of RsmA activity.ImportanceP. aeruginosais an opportunistic multi-drug resistance pathogen that is associated with hospital acquired infections.P. aeruginosais highly virulent, in part due to its versatile metabolism and ability to form biofilms. Therefore, better understanding of the molecular mechanisms that regulate these processes should lead to new therapeutics to treatP. aeruginosainfections. The histidine kinase NahK has been previously shown to be involved in both NO signaling and quorum sensing through RsmA. The data presented here demonstrate that NahK is responsive to NO produced during denitrification to regulate cell morphology. Understanding NahK’s role in metabolism under anaerobic conditions has larger implications in determining Nahk’s role in a heterogeneous metabolic environment such as a biofilm.

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Section: Methodsmentioning

confidence: 99%

The Histidine Kinase NahK Regulates Denitrification and Nitric Oxide Accumulation through RsmA inPseudomonas aeruginosa

Guercio,

Boon

2024

Preprint

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“…NO has been shown to affect biofilm formation and dispersal in a wide variety of gram-negative and gram-positive bacteria, a topic which has been well reviewed recently [18,27,129]. In P. aeruginosa, biofilm dispersal was induced by NO at very low concentrations, while a mutant lacking the only NO former did not disperse from biofilms, and a mutant deficient in NO scavenger exhibited enhanced dispersal [130,131]. Similarly, NO inhibited biofilm formation in Vibrio fischeri [132].…”

Section: Regulation Of Bacterial Communitiesmentioning

confidence: 99%

Nitric Oxide, Nitric Oxide Formers and Their Physiological Impacts in Bacteria

Chen

Liu

Wang

et al. 2022

IJMS

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Nitric oxide (NO) is an active and critical nitrogen oxide in the microbe-driven nitrogen biogeochemical cycle, and is of great interest to medicine and the biological sciences. As a gas molecule prior to oxygen, NO respiration represents an early form of energy generation via various reactions in prokaryotes. Major enzymes for endogenous NO formation known to date include two types of nitrite reductases in denitrification, hydroxylamine oxidoreductase in ammonia oxidation, and NO synthases (NOSs). While the former two play critical roles in shaping electron transport pathways in bacteria, NOSs are intracellular enzymes catalyzing metabolism of certain amino acids and have been extensively studied in mammals. NO interacts with numerous cellular targets, most of which are redox-active proteins. Doing so, NO plays harmful and beneficial roles by affecting diverse biological processes within bacterial physiology. Here, we discuss recent advances in the field, including NO-forming enzymes, the molecular mechanisms by which these enzymes function, physiological roles of bacterial NOSs, and regulation of NO homeostasis in bacteria.

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“…In addition, heme also enters cell signaling circuits by acting as a cofactor of heme-based gas/redox sensors or binding reversely to labile heme-sensing proteins. 4 Hemebased gas sensing and labile heme-sensing have been implicated in regulating many bacterial physiological processes.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Upon internalization, heme can be degraded by heme oxygenases to release ferrous iron or bind to heme-dependent enzymes such as cytochromes, catalases, and nitric oxide reductases. In addition, heme also enters cell signaling circuits by acting as a cofactor of heme-based gas/redox sensors or binding reversely to labile heme-sensing proteins . Heme-based gas sensing and labile heme-sensing have been implicated in regulating many bacterial physiological processes.…”

Section: Introductionmentioning

confidence: 99%

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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Recent Evidence for Multifactorial Biofilm Regulation by Heme Sensor Proteins NosP and H-NOX

Cited by 5 publications

References 94 publications

The Histidine Kinase NahK Regulates Denitrification and Nitric Oxide Accumulation through RsmA inPseudomonas aeruginosa

The Histidine Kinase NahK Regulates Denitrification and Nitric Oxide Accumulation through RsmA inPseudomonas aeruginosa

Nitric Oxide, Nitric Oxide Formers and Their Physiological Impacts in Bacteria

NosP Detection of Heme Modulates Burkholderia thailandensis Biofilm Formation

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