Mutation in mexR-gene leading to drug resistance in corneal keratitis in human.
The present study deals with the genetic polymorphism of the mexR gene which is involved in the resistance to drugs like ciprofloxacin. Mutations in mexR result in increased resistance to multiple antibiotics due to overexpression of this efflux system. The MexR product contains 147 amino acids with a molecular mass of 16,964 Da. We detected 28 point mutations in 14 samples from corneal scraping infected with Pseudomonas aeruginosa, which were screened for ciprofloxacin resistance. Twenty four were silent mutations and four missense mutations. Mapping these mutations was done by using in silico methods on the protein 3D- structure obtained from PDB database, localized at 3 specific sites. Single amino acid changes (mutations) may influence MexR stability or its ability to dimerise, and thus result in the conformation changes at the DNA-binding domain, of the structure. Hence it is concluded that the mutations in the DNA binding domain of mexR gene could be one of the factors contributing to the possible drug resistance in these patients.
Suman
G
G
Genetics Department, Bhagawan Mahavir Hospital and Research Center, 10-1-1, Masab tank, Hyderabad 500 004, India.
Khan
M
M
Sabitha
K
K
Jamil
Kaiser
K
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002939:Ciprofloxacin / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D006801:Humans; D007634:Keratitis / Q000188:drug therapy* / Q000382:microbiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; C423620:MexR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D002939:Ciprofloxacin