Cyclic AMP-Independent Control of Twitching Motility in Pseudomonas aeruginosa

ABSTRACT FimV is a Pseudomonas aeruginosa inner membrane hub protein that modulates levels of the second messenger, cyclic AMP (cAMP), through the activation of adenylate cyclase CyaB. Although type IVa pilus (T4aP)-dependent twitching motility is modulated by cAMP levels, mutants lacking FimV are twitching impaired, even when exogenous cAMP is provided. Here we further define FimV's cAMP-dependent and -independent regulation of twitching. We confirmed that the response regulator of the T4aP-associated Chp chemotaxis system, PilG, requires both FimV and the CyaB regulator, FimL, to activate CyaB. However, in cAMP-replete backgrounds—lacking the cAMP phosphodiesterase CpdA or the CheY-like protein PilH or expressing constitutively active CyaB—pilG and fimV mutants failed to twitch. Both cytoplasmic and periplasmic domains of FimV were important for its cAMP-dependent and -independent roles, while its septal peptidoglycan-targeting LysM motif was required only for twitching motility. Polar localization of the sensor kinase PilS, a key regulator of transcription of the major pilin, was FimV dependent. However, unlike its homologues in other species that localize flagellar system components, FimV was not required for swimming motility. These data provide further evidence to support FimV's role as a key hub protein that coordinates the polar localization and function of multiple structural and regulatory proteins involved in P. aeruginosa twitching motility. IMPORTANCE Pseudomonas aeruginosa is a serious opportunistic pathogen. Type IVa pili (T4aP) are important for its virulence, because they mediate dissemination and invasion via twitching motility and are involved in surface sensing, which modulates pathogenicity via changes in cAMP levels. Here we show that the hub protein FimV and the response regulator of the Chp system, PilG, regulate twitching independently of their roles in the modulation of cAMP synthesis. These functions do not require the putative scaffold protein FimL, proposed to link PilG with FimV. PilG may regulate asymmetric functioning of the T4aP system to allow for directional movement, while FimV appears to localize both structural and regulatory elements—including the PilSR two-component system—to cell poles for optimal function.

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cAMP-independent control of twitching motility inPseudomonas aeruginosa

10.1101/116954 ◽

2017 ◽

Author(s):

Ryan N.C. Buensuceso ◽

Martin Daniel-Ivad ◽

Sara L.N. Kilmury ◽

Hanjeong Harvey ◽

P. Lynne Howell ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Response Regulator ◽

Opportunistic Pathogen ◽

Regulatory Elements ◽

Twitching Motility ◽

Camp Phosphodiesterase ◽

Polar Localization ◽

And Function ◽

Chemotaxis System ◽

Camp Levels

ABSTRACTFimV is aPseudomonas aeruginosainner membrane hub protein that modulates levels of the second messenger, cyclic AMP (cAMP), through activation of the adenylate cyclase, CyaB. Although type IVa pilus (T4aP)-dependent twitching motility is modulated by cAMP levels, mutants lacking FimV are twitching impaired, even when exogenous cAMP is provided. Here we further define FimV’s cAMP-dependent and -independent regulation of twitching. We confirmed that the response regulator of the T4aP-associated Chp chemotaxis system, PilG, required both FimV and the CyaB regulator, FimL, to activate CyaB. However, in cAMP-replete backgrounds - lacking the cAMP phosphodiesterase CpdA or the CheY-like protein PilH, or expressing constitutively-active CyaB -pilGandfimVmutants failed to twitch. Both cytoplasmic and periplasmic domains of FimV were important for its cAMP-dependent and -independent roles, while its septal peptidoglycan-targeting LysM motif was required only for twitching motility. Polar localization of the sensor kinase PilS, a key regulator of transcription of the major pilin, was FimV-dependent. However, unlike its homologues in other species that localize flagellar system components, FimV was not required for swimming motility. These data provide further evidence to support FimV’s role as a key hub protein that coordinates the polar localization and function of multiple structural and regulatory proteins involved inP. aeruginosatwitching motility.IMPORTANCEPseudomonas aeruginosais a serious opportunistic pathogen. Type IVa pili (T4aP) are important for its virulence, because they mediate dissemination and invasion via twitching motility, and are involved in surface sensing which modulates pathogenicity via changes in cAMP levels. Here we show that the hub protein FimV and the response regulator of the Chp system, PilG, regulate twitching independently of their roles in modulation of cAMP synthesis. These functions do not require the putative scaffold protein FimL, proposed to link PilG with FimV. PilG may regulate asymmetric functioning of the T4aP system to allow for directional movement, while FimV appears to localize both structural and regulatory elements – including the PilSR two-component system – to cell poles for optimal function.

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Disparate Subcellular Localization Patterns of Pseudomonas aeruginosa Type IV Pilus ATPases Involved in Twitching Motility

Journal of Bacteriology ◽

10.1128/jb.187.3.829-839.2005 ◽

2005 ◽

Vol 187 (3) ◽

pp. 829-839 ◽

Cited By ~ 87

Author(s):

Poney Chiang ◽

Marc Habash ◽

Lori L. Burrows

Keyword(s):

Pseudomonas Aeruginosa ◽

Fluorescent Protein ◽

Protein Localization ◽

Yellow Fluorescent Protein ◽

Distribution Patterns ◽

Opportunistic Pathogen ◽

Twitching Motility ◽

Polar Localization ◽

Type Iv ◽

And Function

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa expresses polar type IV pili (TFP), which are responsible for adhesion to various materials and twitching motility on surfaces. Twitching occurs by alternate extension and retraction of TFP, which arise from assembly and disassembly of pilin subunits at the base of the pilus. The ATPase PilB promotes pilin assembly, while the ATPase PilT or PilU or both promote pilin dissociation. Fluorescent fusions to two of the three ATPases (PilT and PilU) were functional, as shown by complementation of the corresponding mutants. PilB and PilT fusions localized to both poles, while PilU fusions localized only to the piliated pole. To identify the portion of the ATPases required for localization, sequential C-terminal deletions of PilT and PilU were generated. The conserved His and Walker B boxes were dispensable for polar localization but were required for twitching motility, showing that localization and function could be uncoupled. Truncated fusions that retained polar localization maintained their distinctive distribution patterns. To dissect the cellular factors involved in establishing polarity, fusion protein localization was monitored with a panel of TFP mutants. The localization of yellow fluorescent protein (YFP)-PilT and YFP-PilU was independent of the subunit PilA, other TFP ATPases, and TFP-associated proteins previously shown to be associated with the membrane or exhibiting polar localization. In contrast, YFP-PilB exhibited diffuse cytoplasmic localization in a pilC mutant, suggesting that PilC is required for polar localization of PilB. Finally, localization studies performed with fluorescent ATPase chimeras of PilT and PilU demonstrated that information responsible for the characteristic localization patterns of the ATPases likely resides in their N termini.

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The Conserved Tetratricopeptide Repeat-Containing C-Terminal Domain of Pseudomonas aeruginosa FimV Is Required for Its Cyclic AMP-Dependent and -Independent Functions

Journal of Bacteriology ◽

10.1128/jb.00322-16 ◽

2016 ◽

Vol 198 (16) ◽

pp. 2263-2274 ◽

Cited By ~ 18

Author(s):

Ryan N. C. Buensuceso ◽

Ylan Nguyen ◽

Kun Zhang ◽

Martin Daniel-Ivad ◽

Seiji N. Sugiman-Marangos ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Cyclic Amp ◽

Tetratricopeptide Repeat ◽

Twitching Motility ◽

Wild Type ◽

Inner Membrane ◽

Content Type ◽

Terminal Domain ◽

C Terminus ◽

Independent Functions

ABSTRACTFimV is aPseudomonas aeruginosainner membrane protein that regulates intracellular cyclic AMP (cAMP) levels—and thus type IV pilus (T4P)-mediated twitching motility and type II secretion (T2S)—by activating the adenylate cyclase CyaB. Its cytoplasmic domain contains three predicted tetratricopeptide repeat (TPR) motifs separated by an unstructured region: two proximal to the inner membrane and one within the “FimV C-terminal domain,” which is highly conserved across diverse homologs. Here, we present the crystal structure of the FimV C terminus, FimV861–919, containing a TPR motif decorated with solvent-exposed, charged side chains, plus a C-terminal capping helix. FimV689, a truncated form lacking this C-terminal motif, did not restore wild-type levels of twitching or surface piliation compared to the full-length protein. FimV689failed to restore wild-type levels of the T4P motor ATPase PilU or T2S, suggesting that it was unable to activate cAMP synthesis. Bacterial two-hybrid analysis showed that TPR3 interacts directly with the CyaB activator, FimL. However, FimV689failed to restore wild-type motility in afimVmutant expressing a constitutively active CyaB (fimV cyaB-R456L), suggesting that the C-terminal motif is also involved in cAMP-independent functions of FimV. The data show that the highly conserved TPR-containing C-terminal domain of FimV is critical for its cAMP-dependent and -independent functions.IMPORTANCEFimV is important for twitching motility and cAMP-dependent virulence gene expression inP. aeruginosa. FimV homologs have been identified in several human pathogens, and their functions are not limited to T4P expression. The C terminus of FimV is remarkably conserved among otherwise very diverse family members, but its role is unknown. We provide here biological evidence for the importance of the C-terminal domain in both cAMP-dependent (through FimL) and -independent functions of FimV. We present X-ray crystal structures of the conserved C-terminal domain and identify a consensus sequence for the C-terminal TPR within the conserved domain. Our data extend our knowledge of FimV's functionally important domains, and the structures and consensus sequences provide a foundation for studies of FimV and its homologs.

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The Two-Component Sensor KinB Acts as a Phosphatase To Regulate Pseudomonas aeruginosa Virulence

Journal of Bacteriology ◽

10.1128/jb.01168-12 ◽

2012 ◽

Vol 194 (23) ◽

pp. 6537-6547 ◽

Cited By ~ 14

Author(s):

Nikhilesh S. Chand ◽

Anne E. Clatworthy ◽

Deborah T. Hung

Keyword(s):

Pseudomonas Aeruginosa ◽

Response Regulator ◽

Opportunistic Pathogen ◽

Regulatory Control ◽

Primary Role ◽

Chronic Infections ◽

Content Type ◽

Two Component ◽

Sense And Respond ◽

Cognate Response Regulator

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that is capable of causing both acute and chronic infections.P. aeruginosavirulence is subject to sophisticated regulatory control by two-component systems that enable it to sense and respond to environmental stimuli. We recently reported that the two-component sensor KinB regulates virulence in acuteP. aeruginosainfection. Furthermore, it regulates acute-virulence-associated phenotypes such as pyocyanin production, elastase production, and motility in a manner independent of its kinase activity. Here we show that KinB regulates virulence through the global sigma factor AlgU, which plays a key role in repressingP. aeruginosaacute-virulence factors, and through its cognate response regulator AlgB. However, we show that rather than phosphorylating AlgB, KinB's primary role in the regulation of virulence is to act as a phosphatase to dephosphorylate AlgB and alleviate phosphorylated AlgB's repression of acute virulence.

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The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP

Journal of Bacteriology ◽

10.1128/jb.00193-15 ◽

2015 ◽

Vol 197 (13) ◽

pp. 2190-2200 ◽

Cited By ~ 34

Author(s):

Henrik Almblad ◽

Joe J. Harrison ◽

Morten Rybtke ◽

Julie Groizeleau ◽

Michael Givskov ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Cyclic Amp ◽

Virulence Factors ◽

Camp Signaling ◽

Direct Result ◽

Chronic Infections ◽

Camp Phosphodiesterase ◽

Camp Content ◽

Content Type ◽

Low Level

ABSTRACTThe opportunistic human pathogenPseudomonas aeruginosaexpresses numerous acute virulence factors in the initial phase of infection, and during long-term colonization it undergoes adaptations that optimize survival in the human host. Adaptive changes that often occur during chronic infection give rise to rugose small colony variants (RSCVs), which are hyper-biofilm-forming mutants that commonly possess mutations that increase production of the biofilm-promoting secondary messenger cyclic di-GMP (c-di-GMP). We show that RSCVs display a decreased production of acute virulence factors as a direct result of elevated c-di-GMP content. Overproduction of c-di-GMP causes a decrease in the transcription of virulence factor genes that are regulated by the global virulence regulator Vfr. The low level of Vfr-dependent transcription is caused by a low level of its coactivator, cyclic AMP (cAMP), which is decreased in response to a high level of c-di-GMP. Mutations that cause reversion of the RSCV phenotype concomitantly reactivate Vfr-cAMP signaling. Attempts to uncover the mechanism underlying the observed c-di-GMP-mediated lowering of cAMP content provided evidence that it is not caused by inhibition of adenylate cyclase production or activity and that it is not caused by activation of cAMP phosphodiesterase activity. In addition to the studies of the RSCVs, we present evidence that the deeper layers of wild-typeP. aeruginosabiofilms have high c-di-GMP levels and low cAMP levels.IMPORTANCEOur work suggests that cross talk between c-di-GMP and cAMP signaling pathways results in downregulation of acute virulence factors inP. aeruginosabiofilm infections. Knowledge about this cross-regulation adds to our understanding of virulence traits and immune evasion byP. aeruginosain chronic infections and may provide new approaches to eradicate biofilm infections.

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Bicarbonate Evokes Reciprocal Changes in Intracellular Cyclic di-GMP and Cyclic AMP Levels in Pseudomonas aeruginosa

Biology ◽

10.3390/biology10060519 ◽

2021 ◽

Vol 10 (6) ◽

pp. 519

Author(s):

Kasidid Ruksakiet ◽

Balázs Stercz ◽

Gergő Tóth ◽

Pongsiri Jaikumpun ◽

Ilona Gróf ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Cyclic Amp ◽

Biofilm Formation ◽

Second Messengers ◽

Brain Heart Infusion ◽

Ambient Air ◽

Dependent Manner ◽

Environmental Signals ◽

Common Causes ◽

Camp Levels

The formation of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) is one of the most common causes of morbidity and mortality in CF patients. Cyclic di-GMP and cyclic AMP are second messengers regulating the bacterial lifestyle transition in response to environmental signals. We aimed to investigate the effects of extracellular pH and bicarbonate on intracellular c-di-GMP and cAMP levels, and on biofilm formation. P. aeruginosa was inoculated in a brain–heart infusion medium supplemented with 25 and 50 mM NaCl in ambient air (pH adjusted to 7.4 and 7.7 respectively), or with 25 and 50 mM NaHCO3 in 5% CO2 (pH 7.4 and 7.7). After 16 h incubation, c-di-GMP and cAMP were extracted and their concentrations determined. Biofilm formation was investigated using an xCelligence real-time cell analyzer and by crystal violet assay. Our results show that HCO3− exposure decreased c-di-GMP and increased cAMP levels in a dose-dependent manner. Biofilm formation was also reduced after 48 h exposure to HCO3−. The reciprocal changes in second messenger concentrations were not influenced by changes in medium pH or osmolality. These findings indicate that HCO3− per se modulates the levels of c-di-GMP and cAMP, thereby inhibiting biofilm formation and promoting the planktonic lifestyle of the bacteria.

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Target (MexB)- and Efflux-Based Mechanisms Decreasing the Effectiveness of the Efflux Pump Inhibitor D13-9001 in Pseudomonas aeruginosa PAO1: Uncovering a New Role for MexMN-OprM in Efflux of β-Lactams and a Novel Regulatory Circuit (MmnRS) Controlling MexMN Expression

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01718-18 ◽

2018 ◽

Vol 63 (2) ◽

pp. e01718-18 ◽

Cited By ~ 1

Author(s):

Srijan Ranjitkar ◽

Adriana K. Jones ◽

Mina Mostafavi ◽

Zachary Zwirko ◽

Oleg Iartchouk ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Efflux Pump ◽

Response Regulator ◽

Heavy Metal Resistance ◽

Metal Resistance ◽

Rna Seq ◽

Efflux Pump Inhibitor ◽

Content Type ◽

Regulatory Circuit ◽

Outer Membrane Channel

ABSTRACT Efflux pumps contribute to antibiotic resistance in Gram-negative pathogens. Correspondingly, efflux pump inhibitors (EPIs) may reverse this resistance. D13-9001 specifically inhibits MexAB-OprM in Pseudomonas aeruginosa. Mutants with decreased susceptibility to MexAB-OprM inhibition by D13-9001 were identified, and these fell into two categories: those with alterations in the target MexB (F628L and ΔV177) and those with an alteration in a putative sensor kinase of unknown function, PA1438 (L172P). The alterations in MexB were consistent with reported structural studies of the D13-9001 interaction with MexB. The PA1438L172P alteration mediated a >150-fold upregulation of MexMN pump gene expression and a >50-fold upregulation of PA1438 and the neighboring response regulator gene, PA1437. We propose that these be renamed mmnR and mmnS for MexMN regulator and MexMN sensor, respectively. MexMN was shown to partner with the outer membrane channel protein OprM and to pump several β-lactams, monobactams, and tazobactam. Upregulated MexMN functionally replaced MexAB-OprM to efflux these compounds but was insusceptible to inhibition by D13-9001. MmnSL172P also mediated a decrease in susceptibility to imipenem and biapenem that was independent of MexMN-OprM. Expression of oprD, encoding the uptake channel for these compounds, was downregulated, suggesting that this channel is also part of the MmnSR regulon. Transcriptome sequencing (RNA-seq) of cells encoding MmnSL172P revealed, among other things, an interrelationship between the regulation of mexMN and genes involved in heavy metal resistance.

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Complete Genome Sequence of Pseudomonas aeruginosa Strain AA2 (LMG 27630), an Early Isolate Recovered from the Airway of a German Cystic Fibrosis Patient

Microbiology Resource Announcements ◽

10.1128/mra.00526-20 ◽

2020 ◽

Vol 9 (26) ◽

Author(s):

Andrea Sass ◽

Tom Coenye

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Respiratory Tract ◽

Cystic Fibrosis Patient ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Opportunistic Pathogen ◽

Content Type ◽

Airway Infections ◽

Early Isolate

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that is able to cause various infections, including airway infections in cystic fibrosis patients. Here, we present the complete closed and annotated genome sequence of P. aeruginosa AA2, an isolate obtained early during infection of the respiratory tract of a German cystic fibrosis patient.

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Spatiotemporal Distribution of Pseudomonas aeruginosa Alkyl Quinolones under Metabolic and Competitive Stress

mSphere ◽

10.1128/msphere.00426-20 ◽

2020 ◽

Vol 5 (4) ◽

Author(s):

Tianyuan Cao ◽

Jonathan V. Sweedler ◽

Paul W. Bohn ◽

Joshua D. Shrout

Keyword(s):

Pseudomonas Aeruginosa ◽

Bacterial Species ◽

Metabolic Stress ◽

Opportunistic Pathogen ◽

Cell Interaction ◽

Chemical Imaging ◽

Carbon Limitation ◽

Bacterial Strains ◽

Content Type ◽

High Level

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen important to diseases such as cystic fibrosis. P. aeruginosa has multiple quorum-sensing (QS) systems, one of which utilizes the signaling molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]). Here, we use hyperspectral Raman imaging to elucidate the spatiotemporal PQS distributions that determine how P. aeruginosa regulates surface colonization and its response to both metabolic stress and competition from other bacterial strains. These chemical imaging experiments illustrate the strong link between environmental challenges, such as metabolic stress caused by nutritional limitations or the presence of another bacterial species, and PQS signaling. Metabolic stress elicits a complex response in which limited nutrients induce the bacteria to produce PQS earlier, but the bacteria may also pause PQS production entirely if the nutrient concentration is too low. Separately, coculturing P. aeruginosa in the proximity of another bacterial species, or its culture supernatant, results in earlier production of PQS. However, these differences in PQS appearance are not observed for all alkyl quinolones (AQs) measured; the spatiotemporal response of 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) is highly uniform for most conditions. These insights on the spatiotemporal distributions of quinolones provide additional perspective on the behavior of P. aeruginosa in response to different environmental cues. IMPORTANCE Alkyl quinolones (AQs), including Pseudomonas quinolone signal (PQS), made by the opportunistic pathogen Pseudomonas aeruginosa have been associated with both population density and stress. The regulation of AQ production is known to be complex, and the stimuli that modulate AQ responses are not fully clear. Here, we have used hyperspectral Raman chemical imaging to examine the temporal and spatial profiles of AQs exhibited by P. aeruginosa under several potentially stressful conditions. We found that metabolic stress, effected by carbon limitation, or competition stress, effected by proximity to other species, resulted in accelerated PQS production. This competition effect did not require cell-to-cell interaction, as evidenced by the fact that the addition of supernatants from either Escherichia coli or Staphylococcus aureus led to early appearance of PQS. Lastly, the fact that these modulations were observed for PQS but not for all AQs suggests a high level of complexity in AQ regulation that remains to be discerned.

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PA0335, a Gene Encoding Histidinol Phosphate Phosphatase, Mediates Histidine Auxotrophy in Pseudomonas aeruginosa

Applied and Environmental Microbiology ◽

10.1128/aem.02593-19 ◽

2019 ◽

Vol 86 (5) ◽

Author(s):

Yulu Wang ◽

Liyue Wang ◽

Jian Zhang ◽

Xintong Duan ◽

Yuqi Feng ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Amino Acid ◽

Opportunistic Pathogen ◽

Growth Defect ◽

Histidine Biosynthesis ◽

Common Amino Acid ◽

Content Type ◽

Growth And Survival ◽

Origin And Evolution ◽

Histidinol Phosphate Phosphatase

ABSTRACT The biosynthesis of histidine, a proteinogenic amino acid, has been extensively studied due to its importance in bacterial growth and survival. Histidinol-phosphate phosphatase (Hol-Pase), which is responsible for the penultimate step of histidine biosynthesis, is generally the last enzyme to be characterized in many bacteria because its origin and evolution are more complex compared to other enzymes in histidine biosynthesis. However, none of the enzymes in histidine biosynthesis, including Hol-Pase, have been characterized in Pseudomonas aeruginosa, which is an important opportunistic Gram-negative pathogen that can cause serious human infections. In our previous work, a transposon mutant of P. aeruginosa was found to display a growth defect on glucose-containing minimal solid medium. In this study, we found that the growth defect was due to incomplete histidine auxotrophy caused by PA0335 inactivation. Subsequently, PA0335 was shown to encode Hol-Pase, and its function and enzymatic activity were investigated using genetic and biochemical methods. In addition to PA0335, the roles of 12 other predicted genes involved in histidine biosynthesis in P. aeruginosa were examined. Among them, hisC2 (PA3165), hisH2 (PA3152), and hisF2 (PA3151) were found to be dispensable for histidine synthesis, whereas hisG (PA4449), hisE (PA5067), hisF1 (PA5140), hisB (PA5143), hisI (PA5066), hisC1 (PA4447), and hisA (PA5141) were essential because deletion of each resulted in complete histidine auxotrophy; similar to the case for PA0335, hisH1 (PA5142) or hisD (PA4448) deletion caused incomplete histidine auxotrophy. Taken together, our results outline the histidine synthesis pathway of P. aeruginosa. IMPORTANCE Histidine is a common amino acid in proteins. Because it plays critical roles in bacterial metabolism, its biosynthetic pathway in many bacteria has been elucidated. However, the pathway remains unclear in Pseudomonas aeruginosa, an important opportunistic pathogen in clinical settings; in particular, there is scant knowledge about histidinol-phosphate phosphatase (Hol-Pase), which has a complex origin and evolution. In this study, P. aeruginosa Hol-Pase was identified and characterized. Furthermore, the roles of all other predicted genes involved in histidine biosynthesis were examined. Our results illustrate the histidine synthesis pathway of P. aeruginosa. The knowledge obtained from this study may help in developing strategies to control P. aeruginosa-related infections. In addition, some enzymes of the histidine synthesis pathway from P. aeruginosa might be used as elements of histidine synthetic biology in other industrial microorganisms.

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