Structure and function of OprD protein in Pseudomonas aeruginosa: from antibiotic resistance to novel therapies.
Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen isolated from patients with nosocomial infections. Due to its intrinsic and acquired antimicrobial resistance, limited classes of antibiotics can be used for the treatment of infection with P. aeruginosa. Of these, the carbapenems are very important; however, the occurrence of carbapenem-resistant strains is gradually increasing over time. Deficiency of the outer membrane protein OprD confers P. aeruginosa a basal level of resistance to carbapenems, especially to imipenem. Functional studies have revealed that loops 2 and 3 in the OprD protein contain the entrance and/or binding sites for imipenem. Therefore, any mutation in loop 2 and/or loop 3 that causes conformational changes could result in carbapenem resistance. OprD is also a common channel for some amino acids and peptides, and competition with carbapenems through the channel may also occur. Furthermore, OprD is a highly regulated protein at transcriptional and post-transcriptional levels by some metals, small bioactive molecules, amino acids, and efflux pump regulators. Because of its hypermutability and highly regulated properties, OprD is thought to be the most prevalent mechanism for carbapenem resistance in P. aeruginosa. Developing new strategies to combat infection with carbapenem-resistant P. aeruginosa lacking OprD is an ongoing challenge.
Division of Respiratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Hui
H
Li
Yi-Feng
YF
Luo
Bryan J
BJ
Williams
Timothy S
TS
Blackwell
Can-Mao
CM
Xie
D000596:Amino Acids / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D015378:Imipenem / Q000378:metabolism / Q000627:therapeutic use; D018272:Porins / Q000737:chemistry* / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D015378:Imipenem