Regulatory mechanism of the oprM gene in colistin resistance of acinetobacter baumannii.

Abstract

BACKGROUND: Colistin resistance in Acinetobacter baumannii (AB) is a serious clinical concern. This study aimed to identify resistance-related genes and assess their effects on resistance, growth, and pathogenicity. METHODS: Bioinformatics combined with machine learning identified candidate genes, validated by quantitative real-time PCR. The oprM gene was deleted in a colistin-resistant strain (COL-R) to obtain COL-R-&#x394;oprM. Minimum inhibitory concentration, growth, and biofilm formation were measured. A mouse lung infection model compared bacterial burden, inflammatory cytokines, and histopathology among the ATCC standard strain, COL-R, and COL-R-&#x394;oprM, with or without colistin. RESULTS: The oprM gene and F3P16_RS16375 were identified as candidate genes, with oprM expression markedly upregulated in induced COL-R. Deletion of oprM reduced the colistin MIC, and impaired biofilm formation. In vivo, COL-R-&#x394;oprM showed lower lung bacterial loads than COL-R strains. Compared with the corresponding infection group, the COL-R-&#x2206;oprM +&#x202f;COL group significantly reduced the expression levels of TNF-&#x3b1;, IL-1&#x3b2;, and IL-6, improved lung tissue damage, and effectively reduced the bacterial load in lung tissue (P&#x202f;<&#x202f;0.01), while there was no significant difference in all aspects of the COL-R +&#x202f;COL group (P&#x202f;>&#x202f;0.05). CONCLUSION: The oprM gene is a crucial determinant of colistin resistance in AB. Its deletion restores colistin susceptibility, impairs biofilm formation, and attenuates virulence. Targeting oprM may provide a promising approach for treating colistin-resistant AB infections.