Upstream region of OprD mutations in imipenem-resistant and imipenem-sensitive Pseudomonas isolates

Abstract

The current study was aimed at investigating the prevalence of the mutations upstream of the oprD coding region and its promoters among imipenem-resistant and sensitive Pseudomonas aeruginosa isolated from educational hospitals in Yazd City, Iran. All isolates were identified by the conventional biochemical tests. Then, the antibiotic resistance of these isolates was determined using the disk diffusion method according to the CLSI guidelines. Also, the E.test was performed to determine the minimum inhibitory concentrations (MIC) of imipenem. The mutations of this gene were recognized by the amplification of this region and subsequently sequenced. Sequencing of the genomic region upstream of oprD these regions were done in the 29 clinical strains. Statistical analysis was done by the statistical software SPSS-18. Seventy (77.7%) of isolates had MIC ≥ 16 and were resistant to imipenem. Mutations of the upstream of the oprD gene and its promoters were seen in 25 (86.2%) isolates and 4 isolates had no mutation. One isolate had a base substitution A→Cat nt 25 in the coding region and this isolate had a point mutation leading to an amino acid change at positions 9 (I→L). Our study results indicated that none of the strains had mutation in Shine-Dalgarno and the point mutations were the most common mutations upstream of the oprD coding region among P. aeruginosa isolates. Mutations were observed in imipenem-resistant isolates and it seems this mechanism is effective in resistance of isolates to imipenem and this confirmed that the indiscriminate use of antibiotic should be controlled.

Evaluation of β-lactamases and Molecular Typing of Pseudomonas aeruginosa Clinical Strains Isolated from Hospitalized Children in Tehran, Iran

“…Among the present study's 80 clinical isolates of P. aeruginosa, 20% were resistant to carbapenems. The resistance range of P. aeruginosa to imipenem in other studies in different regions was 5.5 to 62.5% (25,(35)(36)(37)(38). Resistance to carbapenems in P. aeruginosa occurs via several mechanisms.…”

“…aeruginosa is an opportunistic pathogen and one of the main causes of acquired and nosocomial infections with limited therapeutic options. Furthermore, treating infections caused by this bacterium is extremely difficult and challenging (25,26).…”

Risk Factors and Outcomes for Multidrug Resistant Pseudomonas aeruginosa Infection in Immunocompromised Patients

“…The phenotypic profile of the included MDR-PSA isolates was representative of our institution during the study period, characterized by high resistance rates to carbapenems (25–45%) and aminoglycosides (20–45%) and VIM (Verona integron-borne metallo-β-lactamase) and GES (Guiana extended-spectrum β-lactamase) as the predominant carbapenemases in a high-endemicity setting for ST175 and ST235 high-risk clones [ 25 ]. Not unexpectedly, a sizeable proportion of imipenem-resistant isolates were still susceptible to meropenem (susceptibility rates of 6.3% and 22.9%, respectively), which would reflect the role of the loss of OprD or mutations in the promoter region of the oprdD gene [ 26 ]. It underlies the importance of knowing the local epidemiology to guide the design of empirical regimen.…”

Advances in Development of Novel Therapeutic Strategies against Multi-Drug Resistant Pseudomonas aeruginosa

“…Reduced permeability caused by downregulated OprD protein appears to be the most common mechanism of intrinsic resistance to carbapenem [67]. Mutations in OprD [68][69][70][71][72] are associated with imipenem resistance and reduced susceptibility to meropenem through the loss of or change in OprD. One study investigated OprD mutations in locally prevalent MDR P. aeruginosa strains in cystic fibrosis of clinical relevance.…”