Co-expression network analysis of virulence genes exoS and exoU of pseudomonas aeruginosa in lower respiratory tract based on histological data expression profiles

Abstract

Objective: To use the gene chip of pseudomonas aeruginosa as a research sample and to explore it at an omics level, aiming at elucidating the co-expression network characteristics of the virulence genes exoS and exoU of pseudomonas aeruginosa in the lower respiratory tract from the perspective of molecular biology and identifying its key regulatory genes.

Methods: From March 2016 to May 2018, 312 patients infected with pseudomonas aeruginosa in the lower respiratory tract who were admitted to Department of Respiratory Medicine of Baogang Hospital and given follow-up treatments in the hospital were selected as subjects by use of cluster sampling. Alveolar lavage fluid and sputum collected from those patients were used as biological specimens. The genes of pseudomonas aeruginosa were detected with the help of oligonucleotide probes to make a pre-processing of chip data. A total of 8 common antibiotics (ceftazidime, gentamicin, piperacillin, amikacin, ciprofloxacin, levofloxacin, doripenem and ticarcillin) against Gram-negative bacteria were selected to determine the drug resistance of biological specimens. MCODE algorithm was used to construct a co-expression network model of the drug-resistance genes focused on exoS/exoU.

Results: The expression level of exoS/exoU in the drug-resistance group was significantly higher than that in the non-resistance group (p < .05). The top 5 differentially expressed genes in the alveolar lavage fluid specimens from the drug-resistance group were RAC1, ITGB1, ITGB5, CRK and IGF1R in the order from high to low. In the sputum specimens, the top 5 differentially expressed genes were RAC1, CRK, IGF1R, ITGB1 and ITGB5. In the alveolar lavage fluid specimens, only RAC1 had a positive correlation with the expression of exoS and exoU (p < .05). In the sputum specimens, RAC1, ITGB1, ITGB5, CRK and IGF1R were positively correlated with the expression of exoS and exoU (p < .05). The genes included in the co-expression network contained exoS, exoU, RAC1, ITGB1, ITGB5, CRK, CAMK2D, RHOA, FLNA, IGF1R, TGFBR2 and FOS. Among them, RAC1 had a highest score in the aspect of regulatory ability (72.00) and the largest number of regulatory genes (6); followed by ITGB1, ITGB5 and CRK genes.

Conclusions: The high expression of exoS and exoU in the sputum specimens suggests that pseudomonas aeruginosa has a higher probability to get resistant to antibiotics; RAC1, ITGB1, ITGB5 and CRK genes may be the key genes that can regulate the expression of exoS and exoU.