Reconstruction of co-expression network of ampC gene as the main factor of Pseudomonas aeruginosa resistance to the new antibiotic Ceftolozane/Tazobactam

Pseudomonas aeruginosa is a Rod-shaped Gram-negative and strict aerobic bacterium that can causes infection in the urinary system, respiratory system, middle membrane of the skin, soft tissues, bacteremia, etc. Ceftolozan-tazobactam (C/T) is an effective antibiotic in controlling of this bacterium. But recently, reports of the emergence of resistant strains have created a serious challenge in the fight against infections caused by P. aeruginosa. ampC is one of the main genes for β-lactamase synthesis. Studies have shown that Ceftolozane-tazobactam has better outer membrane permeability and improved stability against chromosomal ampC β-lactamase than do other β-lactam antibiotics. Considering the importance of ampC in the process of P. aeruginosa resistance to the Ceftolozane-tazobactam antibiotic, the co-expression network of ampC was reconstructed and the resistance emerging process was analyzed. 31 genes in the beta-lactamase process in P. aeruginosa showed correlation with ampC. Network topology analyzes showed that five genes ampC, ampD, poxB, ampR and nagZ have the highest importance in the network. ampC gene had the highest number of direct connections with other genes in the network with 16 connections. Eight pathways had the highest number of representatives among genes. Based on the statistical analysis of the significant pathways among the studied genes, it seems there is a direct relationship between pyruvate metabolism and resistance to β-lactam antibiotics. Results showed ampC is the main gene for resistance to Ceftolozane-tazobactam. Although studies have shown that poxA and poxB genes do not have a significant effect on P. aeruginosa resistance to the antibiotics, the importance of these two genes in the reconstructed network emphasizes that more studies should be conducted on them.