Jie Fu | PubMed Health

PubMed2026

Involvement of cross-genus phages in bacterial resistance to chlorine disinfection.

Chlorine disinfection resistance in pathogenic microorganisms poses severe environmental concerns and public health risks. While phages play critical roles in host adaptation to environmental stress, how poly-host phages contribute to bacterial resistance to chlorine disinfectants remains poorly understood. Here, we investigated shifts in the population dynamics, transcriptional profiles, and function potentials of cross-genus phage-bacterial communities under exposure to chlorine disinfectants in a continuously operated anaerobic-anoxic-oxic system over a 92-day period, using integrated metagenomic and metatranscriptomic approaches. In the presence and absence of chlorine disinfectants, the genomic abundance and diversity of phage and bacterial communities showed similar variation trends, and the community structures of both exhibited clear differences. A strong significant positive correlation was observed between phage and bacterial diversity under chlorine exposure (R = 0.975, p = 0.00,057), whereas no significant correlation was detected in the absence of chlorine disinfection (R = -0.314, p = 0.613), suggesting that chlorine disinfectants may enhance phage-bacteria interactions. Host-associated phages exhibited high consistency with their corresponding putative hosts in terms of genomic abundance (M2 = 0.0945, p = 0.001) and transcript abundance (M2 = 0.3668, p = 0.001), and they were also significantly correlated with cross-genus phages in both genomic abundance (R = 0.97, p < 2.2e-16) and transcript abundance (R = 0.83, p < 2.2e-16), which collectively suggests the critical role of cross-genus phages in the resistance of microbial communities to chlorine disinfectants. Bipartite association network analysis shows that cross-genus phages carry highly homologous genes to their putative hosts and may be involved in the horizontal transfer of these genes among bacteria. These homologous genes are involved in DNA repair, redox balance regulation, environmental stress adaptation and efflux pump functions, suggesting a synergistic role between cross-genus phages and their putative hosts in chlorine resistance. Our findings reveal that cross-genus phages can contribute to the resistance of bacterial communities to chlorine disinfectants, providing the theoretical foundation for evaluating the role of poly-host phages in microbial communities.

Chlorine resistance↗

PubMed2024

Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models.

Bone cancer pain (BCP) affects ~70% of patients in advanced stages, primarily due to bone metastasis, presenting a substantial therapeutic challenge. Here, we profile orphan G protein-coupled receptors in the dorsal root ganglia (DRG) following tumor infiltration, and observe a notable increase in GPR160 expression. Elevated Gpr160 mRNA and protein levels persist from postoperative day 6 for over 18 days in the affected DRG, predominantly in small-diameter C-fiber type neurons specific to the tibia. Targeted interventions, including DRG microinjection of siRNA or AAV delivery, mitigate mechanical allodynia, cold, and heat hyperalgesia induced by the tumor. Tumor infiltration increases DRG neuron excitability in wild-type mice, but not in Gpr160 gene knockout mice. Tumor infiltration results in reduced H3K27me3 and increased H3K27ac modifications, enhanced binding of the transcription activator Sp1 to the Gpr160 gene promoter region, and induction of GPR160 expression. Modulating histone-modifying enzymes effectively alleviated pain behavior. Our study delineates a novel mechanism wherein elevated Sp1 levels facilitate Gpr160 gene transcription in nociceptive DRG neurons during BCP in rodents.

Animals↗