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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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