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www.benisonmedia.com  ARTICLE  inflammation or help restore   mammary epithelial cells   metabolic disease. During

 Think Grain Think Feed - Volume 11 | Issue 12 | Oct 2025




 infection, glycolysis
 offers a promising route to
 redox balance and limit
 designing multi-epitope
 tissue injury.
 intensifies, with HK, PFK, and
 Linking Infection and
 constructs that specifically
 supply and inflammatory
 Metabolism: The TLR4–NF-
 κB Axis  vaccines and diagnostic   PKM fuelling both energy
 target key glycolytic enzymes  signalling. At the same time,
 Pathogen-associated signals   in cattle, forming the basis of   the TCA cycle becomes
 are key drivers of the   affordable diagnostic strips   disrupted, releasing
 metabolic rewiring observed   or ELISA kits for early   metabolites such as
 during mastitis. In particular,   mastitis detection.  succinate, which amplifies
 Gram-negative bacteria   Parallel computational   inflammation, and itaconate,
 release lipopolysaccharide   docking has highlighted   which tempers it. The
 (LPS), which is recognized by   small molecules such as 2-  pentose phosphate pathway
 Toll-like receptor 4 (TLR4) on   deoxy-D-glucose,   (PPP) accelerates to generate
 mammary epithelial and   Lonidamide, Metformin, and   NADPH, feeding both
 immune cells.   sugar analogs as potential   antimicrobial defences and
 LPS binds to LPS-binding   metabolic inhibitors with   damaging bursts of ROS.
 protein and CD14, then   strong predicted binding   Among various regulators,
 activates the TLR4–MD2   affinities. These leads   PFKFB3 stands out as a
 complex. This recruits MyD88  resonate with experimental   central switch that links
 and activates NF-κB, which   findings showing that   infection-driven metabolic
 enters the nucleus and   inhibition of PFKFB3, for   rewiring to inflammation.
 switches on genes for   example with PFK15, can   Emerging tools such as
 cytokines such as TNF-α and   reduce both inflammation   epitope mapping and in
 IL-6 (Chow et al., 1999;   and bacterial burden in   silico docking provide a
 Medzhitov, 2009; Akhtar et   mastitis (Gao et al., 2024)   foundation for translating
 al., 2020). Beyond its role in   and in sepsis (Xiao et al.,   these molecular insights into
 cytokine production, NF-κB   2023).  practice, designing
 also stimulates glycolysis,   Together, these strategies   diagnostics that detect
 establishing a feed-forward   suggest that metabolic   disease earlier and metabolic
 loop in which infection   enzymes may serve dual   interventions that reduce
 amplifies metabolism and   purposes: as diagnostic   reliance on antibiotics. Taken
 heightened metabolism   biomarkers for subclinical   together, this integrated view
 further sustains inflammation  mastitis and as therapeutic   of infection and metabolism
 (Sordillo, 2018; Zhao et al.,   targets for precision   points toward a new
 2022a, 2022b). This tight   interventions. This approach   paradigm in mastitis
 coupling of immune   paves the way toward farm-  management: shifting from
 signalling and metabolic flux   ready solutions that move   symptom control to
 highlights why mastitis   beyond antibiotics,   proactive monitoring and
 should be viewed not merely   combining early detection   metabolic modulation,
 as a localized udder infection  with therapies designed to   enabling earlier detection,
 but as a systemic   fine-tune glycolysis and   more precise therapies, and
 metabolic–immune disorder.  restore immune–metabolic   sustainable improvement in
 From Computational Leads   balance.  udder health.
 to Farm Solutions  Conclusion  References are available
 Epitope mapping of HK and   Mastitis should be   upon request.
 PFK isoforms (HK II and   understood not only as a
 PFKP) expressed in   bacterial infection but as a
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