Differential expression of ompC and ompF in multidrug-resistant Shigella dysenteriae and Shigella flexneri by aqueous extract of Aegle marmelos, altering its susceptibility toward β-lactam antibiotics

Abstract

Steadily increasing resistance among Shigella to β-lactams, aminoglycosides, and tetracycline has compromised the utility of these commonly used antimicrobial agents. Also, undesirable side effects of certain antibiotics have triggered immense interest in search of alternative therapies using medicinal plants. One such medicinal plant used since ancient times to cure diarrhea is Aegle marmelos. The present study exemplifies the susceptibility of β-lactam–resistant Shigella dysenteriae and Shigella flexneri toward β-lactam antibiotics, when grown in the presence of aqueous extract of A. marmelos (AEAM), by altering porin channels. This was demonstrated by antibiotic sensitivity test using disc diffusion method and MIC test. Susceptibility toward β-lactam antibiotic is associated with changes in outer membrane porins OmpC (∼42 kDa) and OmpF (∼38 kDa) and cytosolic proteins of ∼26 kDa, OmpR, a transcriptional regulator. Expression of ompF is increased in S. dysenteriae and S. flexneri grown in the presence of AEAM due to down-regulation of ompR, which is conformed by reverse transcriptase polymerase chain reaction. In conclusion, AEAM influences susceptibility of β-lactam–resistant Shigella toward β-lactam antibiotics by altering porin channels. Hence, AEAM along with β-lactam can be used for treatment of multidrug-resistant Shigella.