SCIENCE@home

Pyrimidine biosynthesis repression fuels cost and survival of trimethoprim/sulfamethoxazole - Resistant E. coli.

Xiaoxia Hao,Guiling Zheng,Huan Li,Shuo Liu,Li Zhu,Dongmei Jiang,Lin Bai

Published 2026 in Journal of Hazardous Materials

ABSTRACT

Decades of extensive application have led to the rapid emergence and global dissemination of trimethoprim/sulfamethoxazole (TMP/SMZ)-resistant strains, yet the associated fitness costs and underlying adaptive mechanisms remain poorly defined. This study systematically investigated the physiological and molecular adaptations of resistant E. coli under 0-0.125/2.375 μg/mL TMP/SMZ stress. In the absence of antibiotics, resistant bacteria (R) incurred significant fitness costs, evidenced by impaired growth, a 30% reduction in biofilm formation, a 47% thicker cell wall, a diminished capacity for carbon source utilization, and altered nitrogen metabolism - characterized by reduced GS yet elevated GDH and Ca²⁺/Mg²⁺-ATPase activities - compared to the susceptible strain (S; P < 0.05). In competitive co-culture, the R was outcompeted (W < 1). Multi-omics analyses revealed the R strain downregulated energy-intensive processes while maintaining primed oxidative stress defenses. Conversely, under 0.125/2.375 μg/mL TMP/SMZ pressure, R strain demonstrated a pronounced survival advantage. While approximately half of the susceptible population lysed, the R strain exhibited enhanced growth, improved capacity for carbon source utilization and superior competitive fitness (W > 1). This adaptive advantage was underpinned by a fundamental metabolic reconfiguration, characterized by: 1) repression of pyrimidine biosynthesis and resource reallocation to the shikimate pathway and polyamine biosynthesis; 2) a shift in central carbon flux from oxidative phosphorylation toward fermentative pathways; and 3) robust activation of glutathione metabolism and NAD(P)H pools to mitigate oxidative stress. This study reveals the fitness cost and stress-response mechanisms of TMP/SMZ-resistant E. coli, providing novel insights into resistance persistence and a theoretical basis for curbing its environmental spread.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-55 of 55 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1