Recombinant Coxiella burnetii 3-oxoacyl-[acyl-carrier-protein] synthase 2 (fabF)

What is Coxiella burnetii 3-oxoacyl-[acyl-carrier-protein] synthase 2 (fabF) and what is its biological significance?

Coxiella burnetii 3-oxoacyl-[acyl-carrier-protein] synthase 2 (fabF) is a key enzyme involved in the fatty acid biosynthesis pathway of this obligate intracellular pathogen. FabF catalyzes the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty acid synthesis . As C. burnetii is the causative agent of Q fever and classified as a category B bio-weapon, understanding its metabolic enzymes is crucial .

The biological significance of fabF in C. burnetii stems from its central role in membrane lipid biosynthesis, which is essential for the pathogen's survival and adaptation within the harsh environment of the Coxiella-containing vacuole (CCV). Given that C. burnetii replicates in an acidic phagolysosomal vacuole, specialized membrane fatty acids likely play critical roles in pH resistance and intracellular survival .

How does C. burnetii fabF compare structurally and functionally to homologous enzymes in other bacteria?

While specific structural information for C. burnetii fabF is limited in the provided search results, we can draw comparisons with related bacterial enzymes. 3-Oxoacyl-ACP synthase II enzymes typically have molecular weights around 43 kDa, as seen in the Thermus thermophilus enzyme (43.2 kDa with 408 amino acid residues) .

What is currently known about the metabolic context of fabF in C. burnetii?

C. burnetii possesses a highly diverse metabolic network that utilizes multiple substrates . Recent isotopolog profiling studies have revealed that C. burnetii can assimilate various carbon sources, which feed into its bipartite metabolic network .

The fatty acid biosynthesis pathway, in which fabF plays a crucial role, is likely essential for the pathogen's ability to establish and maintain its replicative niche. The fabrication of specialized membrane lipids through this pathway may contribute to the stability and functionality of the CCV, which occupies a significant portion of the host cell's volume during infection . Understanding how fabF contributes to membrane composition could provide insights into how C. burnetii maintains the integrity of its massive CCV during intracellular replication.

What are the optimal expression systems for producing recombinant C. burnetii fabF?

For recombinant expression of C. burnetii fabF, several expression systems can be considered:

E. coli-based expression system:

• Recommended strain: BL21(DE3) or Rosetta 2(DE3) for rare codon optimization

• Vector options: pET-28a(+) with N-terminal His-tag for efficient purification

• Induction conditions: 0.5-1.0 mM IPTG at reduced temperature (16-18°C) for 16-20 hours to enhance soluble protein yield

• Media: Terrific Broth supplemented with appropriate antibiotics

Cell-free expression system:

• Particularly useful if the protein forms inclusion bodies in conventional systems

• Allows incorporation of detergents or lipids to stabilize membrane-associated domains

The decision between these systems should be based on preliminary solubility testing. For C. burnetii proteins, which may have adapted to an acidic intracellular environment, expression conditions may need optimization to maintain proper folding and function.

What purification protocol yields the highest purity and activity for recombinant C. burnetii fabF?

A multi-step purification protocol is recommended:

Table 1: Recommended Purification Protocol for C. burnetii fabF

Critical considerations:

• Include protease inhibitors in all buffers to prevent degradation

• Add 1-5 mM DTT or 0.5-2 mM TCEP to maintain cysteine residues in reduced state

• Consider including 10% glycerol in final storage buffer to maintain stability

• Aliquot and flash-freeze in liquid nitrogen for long-term storage at -80°C

This protocol should be optimized based on preliminary characterization of protein behavior. Activity assays should be performed after each purification step to ensure the protein remains functional.

How can I evaluate the proper folding and activity of purified recombinant C. burnetii fabF?

Multiple complementary approaches should be used:

Structural integrity assessment:

• Circular dichroism (CD) spectroscopy to analyze secondary structure content

• Thermal shift assays to determine protein stability and identify stabilizing buffer conditions

• Dynamic light scattering to assess monodispersity and detect aggregation

Functional assays:

• Spectrophotometric assay measuring the condensation reaction with malonyl-ACP and acyl-ACP substrates

• Radio-labeled substrate incorporation assays for direct quantification of enzymatic activity

• HPLC-based assays to monitor product formation

Activity validation parameters:

• Determine Km and Vmax values for key substrates

• Assess temperature and pH optima (particularly important for C. burnetii proteins which function in acidic environments)

• Evaluate the effects of potential inhibitors on enzyme activity

Comparing the kinetic parameters with those of fabF from other bacteria can provide insights into C. burnetii-specific adaptations related to its intracellular lifestyle.

What structural features distinguish C. burnetii fabF from homologous enzymes in other bacteria?

While specific structural data for C. burnetii fabF is not provided in the search results, we can predict distinguishing features based on the organism's unique lifestyle:

• Acid stability adaptations: As C. burnetii thrives in acidic phagolysosomal vacuoles, its fabF likely possesses structural modifications that enhance stability under acidic conditions. These may include:

  • Increased surface negative charge distribution to repel protons

  • Reduced number of acid-labile bonds

  • Strategic distribution of histidine residues with altered pKa values

• Substrate binding pocket variations: The substrate specificity of C. burnetii fabF may differ from that of other bacteria, reflecting adaptations to the intracellular environment and substrate availability within the CCV.

• Potential regulatory domains: Given C. burnetii's complex metabolic network that utilizes multiple substrates , its fabF might contain unique regulatory regions that respond to intracellular environmental cues.

Comparative structural analysis with other bacterial fabF enzymes, such as the T. thermophilus enzyme mentioned in the search results , would be valuable for identifying these distinguishing features.

What crystallization conditions are optimal for obtaining diffraction-quality crystals of C. burnetii fabF?

Based on successful crystallization of related 3-oxoacyl-ACP synthases, including the one from T. thermophilus , the following screening approach is recommended:

Initial screening conditions:

• Temperature: 18°C and 4°C in parallel

• Protein concentration: 5-15 mg/ml range

• Buffer systems: 100 mM HEPES (pH 7.0-7.5) or 100 mM MES (pH 6.0-6.5) to mimic physiological pH ranges

• Precipitants: PEG series (PEG 3350, PEG 4000, PEG 8000) at 10-25% concentrations

• Salt additives: 200 mM lithium sulfate, ammonium sulfate, or sodium chloride

Optimization strategies:

• Microseeding to improve crystal quality and size

• Hanging-drop and sitting-drop vapor diffusion in parallel

• Consider inclusion of substrate analogs or inhibitors to stabilize the protein

• Addition of 10-15% glycerol or similar cryoprotectants directly in crystallization condition

Co-crystallization considerations:

• Including catalytically inactive substrate analogs

• Testing with ACP substrate or mimics to capture physiologically relevant states

Success in crystallization will likely require extensive screening and optimization, particularly given the potential adaptations of C. burnetii fabF to acidic environments.

How can computational modeling complement experimental structural studies of C. burnetii fabF?

Computational approaches offer valuable insights when experimental structural data is limited:

• Homology modeling:

  • Use structurally characterized bacterial fabF enzymes (like the T. thermophilus homolog ) as templates

  • Improve model quality through energy minimization and molecular dynamics simulations

  • Validate models using Ramachandran plot analysis and ProSA-web scores

• Molecular dynamics simulations:

  • Assess protein stability under various pH conditions to investigate acid adaptation

  • Evaluate substrate binding dynamics and identify key interaction residues

  • Simulate conformational changes during catalytic cycles

• Virtual screening for inhibitors:

  • Generate pharmacophore models based on known β-ketoacyl-ACP synthase inhibitors

  • Perform structure-based virtual screening to identify potential antimicrobial compounds

  • Predict binding modes and affinities of candidate inhibitors

• Integration with experimental data:

  • Refine models based on limited experimental data (CD spectroscopy, HDX-MS)

  • Guide mutagenesis experiments by identifying functionally important residues

  • Predict the impact of amino acid substitutions on enzyme activity and stability

This integrated computational-experimental approach is particularly valuable for difficult-to-crystallize proteins from pathogens like C. burnetii.

What are the most effective assays for measuring C. burnetii fabF enzymatic activity?

Multiple complementary assays can be employed to characterize C. burnetii fabF activity:

Spectrophotometric coupled assays:

• Monitor the release of CoA via reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) at 412 nm

• Couple the reaction to ACP consumption through fluorescently labeled ACP

Radioactive assays:

• Use [14C]-malonyl-CoA to monitor incorporation into growing fatty acid chains

• Quantify radiolabeled products via TLC separation followed by autoradiography

LC-MS based assays:

• Direct detection of acyl-ACP products with different chain lengths

• Identification of specific fatty acid profiles produced under various conditions

Table 2: Comparison of fabF Activity Assay Methods

When characterizing C. burnetii fabF, it's particularly important to assess activity under acidic conditions (pH 4.5-5.5) that mimic its native phagolysosomal environment, in addition to standard conditions.

How does the catalytic activity of C. burnetii fabF differ from FabF of other bacteria under varying pH and temperature conditions?

While specific comparative data is not provided in the search results, we can outline an experimental approach to address this question:

pH profile determination:

• Test enzymatic activity across pH range 4.0-9.0 using appropriate buffer systems

• Compare with E. coli and other bacterial fabF enzymes under identical conditions

• Hypothesize: C. burnetii fabF likely maintains higher relative activity at acidic pH (4.5-5.5) compared to homologs from neutralophilic bacteria

Temperature profile analysis:

• Assess activity at temperatures ranging from 25°C to 50°C

• Determine thermal stability through inactivation kinetics studies

• Compare thermostability with the T. thermophilus enzyme (which likely has high thermostability)

Expected differences:

• C. burnetii fabF likely exhibits adaptive features for function in acidic environments

• The enzyme may show altered substrate specificity reflecting the intracellular availability of precursors

• Regulatory mechanisms may differ from those of free-living bacteria

These comparative studies would provide insights into how C. burnetii has adapted its fatty acid biosynthesis machinery to its unique intracellular lifestyle and the acidic environment of the CCV.

What is the role of fabF in C. burnetii's ability to establish and maintain its intracellular niche?

While direct experimental evidence on C. burnetii fabF's role in pathogenesis is not detailed in the search results, we can propose the following based on general bacterial physiology and specific information about C. burnetii:

• Membrane lipid composition adaptation:

  • FabF likely contributes to the synthesis of specialized fatty acids that are incorporated into phospholipids essential for CCV membrane integrity

  • These adaptations may help maintain the massive CCV structure, which can occupy the majority of the host cell's volume

• Survival in acidic environment:

  • Specialized membrane fatty acids synthesized through the fabF pathway may contribute to acid resistance

  • The composition of membrane lipids directly impacts proton permeability and cellular pH homeostasis

• Interface with host cell metabolism:

  • C. burnetii has a diverse metabolic network utilizing multiple substrates

  • FabF may represent a metabolic adaptation point, allowing the bacterium to utilize host-derived precursors for fatty acid synthesis

• Potential coordination with T4SS:

  • C. burnetii's type IV secretion system (T4SS) is crucial for establishing the CCV

  • Membrane lipids produced through the fabF pathway may interact with or support T4SS function

Experimental approaches to verify these proposed roles could include:

• Creating conditional fabF mutants and assessing CCV formation

• Lipidomic analysis comparing wild-type and fabF-depleted C. burnetii

• Examining membrane properties and acidic resistance in strains with altered fabF expression

How does fabF activity contribute to C. burnetii's pathogenicity and virulence?

Based on understanding bacterial pathogenesis and fatty acid metabolism, we can propose several mechanisms by which fabF may contribute to C. burnetii's virulence:

• Membrane integrity and stress resistance:

  • FabF-synthesized fatty acids are incorporated into membrane phospholipids that help withstand the harsh phagolysosomal environment

  • This adaptation is crucial for surviving in the acidic CCV, a characteristic feature of C. burnetii infection

• Lipid-based immune modulation:

  • Specific lipid compositions may help C. burnetii evade host immune detection

  • The phase variation between "smooth" and "rough" LPS types mentioned in the search results may involve fabF-dependent changes in lipid biosynthesis

• Energy storage and metabolic flexibility:

  • FabF contributes to the synthesis of fatty acids that serve as energy reserves

  • This supports C. burnetii's ability to persist in various environments and transition between developmental forms

• Interface with T4SS function:

  • Proper membrane composition, influenced by fabF activity, may be necessary for the optimal function of the T4SS, which is essential for delivering effector proteins like AnkF into host cells

  • The search results indicate that the T4SS effector AnkF is important for intracellular replication

Experimental approaches to validate these hypotheses could include comparing the virulence of wild-type C. burnetii with strains having altered fabF expression in cellular and animal models of Q fever.

What is the relationship between fabF activity and C. burnetii's ability to adapt to the phagolysosomal environment?

The ability of C. burnetii to not just survive but thrive within the acidic phagolysosomal environment is central to its pathogenesis. FabF likely plays several key roles in this adaptation:

• Acid-resistant membrane composition:

  • FabF-dependent fatty acid synthesis contributes to a membrane lipid composition that maintains integrity under acidic stress

  • The specific fatty acid profile may reduce proton permeability and help maintain cellular pH homeostasis

• Support for CCV expansion:

  • As the CCV expands to "occupy the majority of the host cell's volume" , membrane synthesis becomes critical

  • FabF activity provides the fatty acid building blocks necessary for this membrane expansion

• Metabolic adaptation to available nutrients:

  • C. burnetii possesses a "highly diverse metabolic network" that utilizes multiple substrates

  • FabF may be regulated to utilize available carbon sources within the phagolysosomal environment

• Coordination with structural support systems:

  • The search results mention that galectins and actin might be involved in ensuring CCV stability

  • Membrane lipid composition, influenced by fabF, may affect recruitment of these structural elements

Research approaches to investigate these relationships could include proteomic and transcriptomic analyses comparing C. burnetii grown in axenic media versus intracellular conditions, focusing on changes in fabF expression and fatty acid biosynthesis pathways.

Could fabF inhibition represent a viable strategy for developing new antimicrobials against C. burnetii?

The search results indicate that β-ketoacyl-ACP synthases like fabF are "promising targets for the development of new antibacterial agents" . Several factors support fabF as a potential drug target against C. burnetii:

Advantages of targeting fabF:

• Essential metabolic function: Fatty acid biosynthesis is likely essential for C. burnetii survival and replication

• Structural targetability: As an enzyme, fabF offers defined active sites for inhibitor binding

• Reduced resistance potential: Target-based resistance might incur significant fitness costs for an intracellular pathogen

• Selectivity potential: Differences between bacterial and human fatty acid synthesis pathways enable selective targeting

Strategic considerations:

• Delivery challenges: Inhibitors must penetrate host cells and the CCV to reach the target

• Synergy potential: Combining fabF inhibitors with current Q fever treatments (doxycycline, hydroxychloroquine) might enhance efficacy

• Repurposing opportunity: Existing antimicrobial compounds targeting fabF in other bacteria could be evaluated against C. burnetii

Table 3: Potential Advantages and Challenges of fabF-Targeted Anti-C. burnetii Therapy

Testing this strategy would require developing cell-based assays that can distinguish between host toxicity and specific anti-C. burnetii activity of potential fabF inhibitors.

How can CRISPR/Cas9 techniques be adapted for modifying the fabF gene in C. burnetii?

Methodological approach:

• Vector design considerations:

  • Create shuttle vectors containing Cas9 under control of the C. burnetii promoter

  • Design sgRNAs targeting fabF with minimal off-target effects

  • Include homology-directed repair templates for precise gene editing

• Delivery methods:

  • Electroporation of CRISPR components into axenically grown C. burnetii (ACCM-2 medium)

  • Package CRISPR components in cell-penetrating peptides for enhanced delivery

  • Consider using host cell-mediated delivery for intracellular bacteria

• Verification strategies:

  • PCR-based genotyping and sequencing to confirm intended modifications

  • Phenotypic characterization using fatty acid profiling

  • Monitoring growth curves in ACCM-2 medium and within host cells

• Research applications:

  • Generate conditional knockdowns to assess essentiality

  • Introduce point mutations to study structure-function relationships

  • Create reporter fusions to monitor fabF expression and regulation

The development of clean deletion mutants, as described for the AnkF effector protein in the search results , could serve as a methodological template for fabF manipulation.

What insights can metabolomics approaches provide about the role of fabF in C. burnetii's metabolic network?

Metabolomics offers powerful approaches to understand fabF's role in C. burnetii's complex metabolic network:

Experimental design for metabolomic studies:

• Sample preparation approaches:

  • Compare wild-type C. burnetii with fabF-modified strains (knockdown or overexpression)

  • Analyze samples from both axenic cultures and intracellular bacteria

  • Include time-course sampling to capture dynamic metabolic shifts

• Analytical techniques:

  • Targeted LC-MS/MS for specific fatty acid intermediates and products

  • Untargeted metabolomics to discover unexpected metabolic connections

  • Isotope tracing experiments using 13C-labeled substrates, similar to those mentioned in search result

• Expected insights:

  • Identification of fabF-dependent fatty acid profiles specific to C. burnetii

  • Elucidation of metabolic rerouting mechanisms when fabF activity is compromised

  • Discovery of connections between fatty acid metabolism and other pathways

• Integration with other omics data:

  • Correlate metabolomic changes with transcriptomic responses

  • Identify regulatory networks controlling fabF expression

  • Map protein-protein interactions involving fabF in the metabolic network

The isotopolog profiling approach mentioned in search result would be particularly valuable for tracing carbon flow through fabF-catalyzed reactions in C. burnetii's "bipartite metabolic network."

How do host cell factors interact with C. burnetii fabF to influence bacterial replication and persistence?

Understanding host-pathogen interactions involving fabF requires investigating several potential mechanisms:

• Host fatty acid availability effects:

  • Design experiments to alter host cell fatty acid composition and monitor impacts on C. burnetii replication

  • Use stable isotope labeling to track incorporation of host-derived fatty acids into bacterial lipids

  • Compare fatty acid uptake versus de novo synthesis via fabF under various conditions

• Interaction with host cytoskeletal elements:

  • The search results indicate that vimentin and other cytoskeletal components are recruited to the CCV

  • Investigate whether membrane composition, influenced by fabF activity, affects these interactions

  • Utilize super-resolution microscopy techniques like STED (mentioned in search result ) to visualize these interactions

• Response to host defense mechanisms:

  • Examine how fabF activity is modulated in response to host-induced stresses

  • Investigate potential interactions between fabF-dependent membrane composition and host antimicrobial factors

  • Analyze fatty acid profiles in response to host immune signaling molecules

• Temporal dynamics during infection:

  • Monitor fabF expression and activity throughout the C. burnetii infection cycle

  • Correlate with CCV maturation stages and bacterial developmental transitions

  • Identify key transition points where fabF activity becomes critical for pathogen success

These investigations would benefit from the application of techniques like those used to study the AnkF effector protein's interactions with host cell components, as described in search result .

How does C. burnetii fabF compare functionally with equivalent enzymes in other intracellular pathogens?

Comparative analysis provides insights into pathogen-specific adaptations:

Methodological approach for comparative studies:

• Sequence and structural comparisons:

  • Perform phylogenetic analysis of fabF across diverse intracellular pathogens

  • Identify conserved catalytic residues versus variable regions

  • Conduct homology modeling to predict structural differences

• Heterologous expression studies:

  • Express fabF genes from different intracellular pathogens in a common host

  • Compare enzymatic parameters and substrate preferences

  • Assess complementation efficiency in fabF-deficient bacterial strains

• Expected differences among intracellular pathogens:

  • Mycobacterium tuberculosis fabF likely shows adaptations for long-term persistence

  • Chlamydia trachomatis may have evolved fabF to function with limited substrate availability

  • Legionella pneumophila fabF might share features with C. burnetii given their phylogenetic relationship mentioned in search result

• Relevance to pathogenesis:

  • Correlate fabF differences with pathogen-specific growth rates and persistence mechanisms

  • Identify unique features that might explain tissue tropism or disease manifestations

  • Evaluate potential as universal versus pathogen-specific drug targets

This comparative approach would help identify which features of C. burnetii fabF represent general adaptations to intracellular life versus specific adaptations to the unique phagolysosomal niche.

What methods can be used to study the evolution of fabF across different Coxiella species and strains?

Evolutionary analysis of fabF provides insights into adaptation mechanisms:

Methodological approaches:

• Phylogenetic analysis:

  • Construct maximum likelihood trees using fabF sequences from diverse Coxiella isolates

  • Calculate selection pressures (dN/dS ratios) to identify regions under positive selection

  • Perform ancestral sequence reconstruction to trace evolutionary trajectories

• Comparative genomics:

  • Analyze synteny and genome context of fabF across Coxiella species

  • Identify horizontal gene transfer events that might have influenced fabF evolution

  • Compare with environmental Coxiella-like organisms to understand pre-adaptation

• Structural biology integration:

  • Map evolutionary changes onto protein structural models

  • Identify co-evolving residues that maintain protein function

  • Predict how sequence variations influence catalytic efficiency and substrate specificity

• Experimental validation:

  • Express ancestral and variant fabF proteins to compare enzymatic properties

  • Test complementation efficiency in heterologous systems

  • Correlate genetic variations with fatty acid profiles and virulence traits

Such evolutionary studies could reveal how C. burnetii fabF has adapted to the unique challenges of obligate intracellular growth and the acidic environment of the CCV.

How do differences in fabF structure and function across bacterial species impact antimicrobial development strategies?

Understanding structural and functional diversity of fabF has important implications for drug development:

Key considerations for structure-based drug design:

• Conservation analysis:

  • Identify highly conserved regions across fabF from diverse pathogens

  • Target these regions for broad-spectrum inhibitor development

  • Map species-specific variations that could affect inhibitor binding

• Active site comparison:

  • Analyze substrate binding pocket differences that might enable selective targeting

  • Design inhibitors exploiting unique features of C. burnetii fabF

  • Consider the impact of the acidic CCV environment on inhibitor binding kinetics

• Resistance mechanism prediction:

  • Identify potential resistance-conferring mutations based on natural fabF variants

  • Design inhibitor scaffolds less susceptible to resistance development

  • Target multiple sites simultaneously to create higher genetic barriers to resistance

• Experimental validation approaches:

  • Test candidate inhibitors against recombinant fabF enzymes from multiple species

  • Utilize thermal shift assays to compare binding affinities across orthologs

  • Employ structure-activity relationship studies to optimize selectivity profiles

Table 4: Strategic Considerations for Anti-fabF Drug Development

This comparative analysis would help develop antimicrobials that effectively target C. burnetii while minimizing impacts on beneficial bacteria or host enzymes.

What are the most promising experimental approaches for studying fabF's role in C. burnetii's life cycle and pathogenesis?

Several cutting-edge approaches could advance our understanding of C. burnetii fabF:

• CRISPRi-based conditional knockdown systems:

  • Develop inducible fabF repression to study essentiality at different life cycle stages

  • Create partial inhibition models to identify threshold levels needed for survival

  • Combine with transcriptomics to identify compensatory mechanisms

• Advanced microscopy techniques:

  • Apply super-resolution microscopy like STED (mentioned in search result ) to visualize fabF localization

  • Use correlative light and electron microscopy to examine membrane structures

  • Implement live-cell imaging with fluorescent fatty acid analogs to track metabolism in real-time

• Single-cell analysis approaches:

  • Develop methods to isolate and analyze individual bacteria from the CCV

  • Apply single-cell transcriptomics to identify population heterogeneity in fabF expression

  • Correlate with bacterial developmental forms and replication states

• In vivo infection models:

  • Utilize animal models of Q fever to study fabF expression during actual infection

  • Develop tissue-specific sampling and analysis methods

  • Correlate fabF activity with disease progression and persistence

These approaches would build upon the methodological foundations described in the search results, particularly the techniques used to study C. burnetii's intracellular niche and the role of effector proteins like AnkF .

What unexplored areas of C. burnetii fatty acid metabolism warrant further investigation?

Several knowledge gaps represent opportunities for groundbreaking research:

• Regulatory networks controlling fabF expression:

  • Identify transcription factors and small RNAs regulating fabF

  • Elucidate environmental signals that modulate fatty acid synthesis

  • Map the integration of fabF regulation with the broader metabolic network

• Temporal dynamics during developmental transitions:

  • C. burnetii undergoes morphological transitions between small cell variant (SCV) and large cell variant (LCV) forms

  • The role of fabF in these transitions remains poorly understood

  • Changes in membrane composition may be critical for these developmental shifts

• Connections with virulence mechanisms:

  • Potential interactions between fabF-dependent membrane composition and T4SS function

  • Role of specific fatty acids in modulating host immune responses

  • Contribution to the phase variation between "smooth" and "rough" LPS types mentioned in search result

• Metabolic interactions with the host:

  • Competition for or scavenging of fatty acid precursors

  • Incorporation of host-derived fatty acids into bacterial membranes

  • Influence on host lipid metabolism and signaling

These investigations would complement the existing work on C. burnetii's "bipartite metabolic network" mentioned in search result and could reveal new therapeutic targets.

How might systems biology approaches enhance our understanding of fabF's position in C. burnetii's metabolic and virulence networks?

Systems biology offers powerful frameworks for integrating diverse data types: