Lactate dynamics at the Pseudomonas aeruginosa–host interface: bacterial metabolism, host defense, and emerging links to histone lactylation
- 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- 2Department of Geriatrics, Jinsha County People’s Hospital, Bijie, Guizhou, China
Abstract
At the Pseudomonas aeruginosa–host interface, lactate is both a host immunometabolic product and a preferred bacterial carbon source. Its local concentration reflects host production, bacterial utilization, transport, and clearance rather than inflammation alone. P. aeruginosa uses D- and L-lactate through stereospecific, conditionally regulated systems. It preferentially consumes lactate in human burn-wound exudate, and this capacity contributes to early intracellular survival in macrophages. Lactate-associated acidity also increases bacterial vesicle release and quinolone signaling, weakening antimicrobial-peptide activity independently of chromatin modification. On the host side, bacterial L-lactate utilization and virulence-factor-associated suppression of epithelial glycolysis lower epithelial lactate and histone H3 lysine 18 lactylation (H3K18la). These changes are linked to disrupted RNA regulation and impaired ciliary clearance. In macrophages, the quorum-sensing signal 2-aminoacetophenone (2-AA) reprograms bioenergetics, autophagy, and lipid metabolism, promoting tolerance and intracellular persistence. A separate hypothesis connecting 2-AA to increased macrophage lactate and H3K18la is supported only by a supplement abstract and requires full-length validation. Histone lactylation is therefore an emerging extension of this biology. This narrative review follows two linked strands: bacterial lactate utilization and lactate-associated changes in host defense. It distinguishes established metabolic effects from proposed lactylation-dependent mechanisms and considers potential therapeutic directions and their trade-offs. These include targeting bacterial lactate utilization, airway acidity, host transport or modification enzymes, and 2-AA-associated tolerance. Any benefit must be assessed against the possibility of supplying bacterial nutrients or worsening host injury.
Related
- Expression of ExsA in trans Confers Type III Secretion System-Dependent Cytotoxicity on Noncytotoxic Pseudomonas aeruginosa Cystic Fibrosis Isolates
- Role of manganese superoxide dismutase in a mucoid isolate of Pseudomonas aeruginosa: adaptation to oxidative stress
- Cell Death of Human Polymorphonuclear Neutrophils Induced by a Pseudomonas aeruginosa Cystic Fibrosis Isolate Requires a Functional Type III Secretion System
- Mechanical compression activates cAMP signaling in Pseudomonas aeruginosa
- Pseudomonas aeruginosa Cystic Fibrosis Isolates Induce Rapid, Type III Secretion-Dependent, but ExoU-Independent, Oncosis of Macrophages and Polymorphonuclear Neutrophils
BibTeX
@article{jian2026lactate,
title = {{Lactate dynamics at the Pseudomonas aeruginosa–host interface: bacterial metabolism, host defense, and emerging links to histone lactylation}},
author = {Yi Jian and Zhijie Wu and Yuqiang Liang and Jin Cao and Mei Li and Fashuang Yang and Ke Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1979311},
url = {https://doi.org/10.3389/fimmu.2026.1979311},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lactate dynamics at the Pseudomonas aeruginosa–host interface: bacterial metabolism, host defense, and emerging links to histone lactylation
AU - Yi Jian
AU - Zhijie Wu
AU - Yuqiang Liang
AU - Jin Cao
AU - Mei Li
AU - Fashuang Yang
AU - Ke Wang
PY - 2026
DA - 2026/10/12
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1979311
UR - https://doi.org/10.3389/fimmu.2026.1979311
AB - At the Pseudomonas aeruginosa–host interface, lactate is both a host immunometabolic product and a preferred bacterial carbon source. Its local concentration reflects host production, bacterial utilization, transport, and clearance rather than inflammation alone. P. aeruginosa uses D- and L-lactate through stereospecific, conditionally regulated systems. It preferentially consumes lactate in human burn-wound exudate, and this capacity contributes to early intracellular survival in macrophages. Lactate-associated acidity also increases bacterial vesicle release and quinolone signaling, weakening antimicrobial-peptide activity independently of chromatin modification. On the host side, bacterial L-lactate utilization and virulence-factor-associated suppression of epithelial glycolysis lower epithelial lactate and histone H3 lysine 18 lactylation (H3K18la). These changes are linked to disrupted RNA regulation and impaired ciliary clearance. In macrophages, the quorum-sensing signal 2-aminoacetophenone (2-AA) reprograms bioenergetics, autophagy, and lipid metabolism, promoting tolerance and intracellular persistence. A separate hypothesis connecting 2-AA to increased macrophage lactate and H3K18la is supported only by a supplement abstract and requires full-length validation. Histone lactylation is therefore an emerging extension of this biology. This narrative review follows two linked strands: bacterial lactate utilization and lactate-associated changes in host defense. It distinguishes established metabolic effects from proposed lactylation-dependent mechanisms and considers potential therapeutic directions and their trade-offs. These include targeting bacterial lactate utilization, airway acidity, host transport or modification enzymes, and 2-AA-associated tolerance. Any benefit must be assessed against the possibility of supplying bacterial nutrients or worsening host injury.
SN - 1664-3224
ER -