A. paniculata has a long history of being utilized as an oriental and Ayurvedic medicine. Genus
Andrographis belongs to the family Acanthaceae which includes around 40 species.
A. paniculata is commonly known as the King of Bitters and is native to peninsular India and Sri Lanka. This plant also occupies different regions of Southeast Asia, China, America, West Indies and Christmas Island. The wide distribution of
A. paniculata accounts for its medicinal values and its growth in most of the soil types. The aerial parts, as well as the roots of
A. paniculata, have served the purpose of traditional medicine in countries like India, China, Thailand and some Southeast Asian countries. Extensive studies have been conducted by researchers across the world and particularly in Asia owing to the medicinal properties of
A. paniculata. Phytochemical analysis of
A. paniculata has unveiled a wide range of compounds such as labdane diterpenoid lactones, flavonoids and miscellaneous compounds.
A. paniculata has also been reported to display a wide range of pharmacological properties [
23]. The antibacterial properties of
A. paniculata extracts have been reported in some previously carried out studies with different bacterial strains. Leelarasamee and co-workers reported a significant antimicrobial activity of crude extract of
A. paniculata against
Salmonella, Shigella, Escherichia coli,
Streptococci, and
Staphylococcus aureus at a concentration of 25 mg/ml [
24]. An investigation conducted by Mishra and co-workers reported the growth inhibitory effect of ethanol extracts of aerial parts of
A. paniculata against
E. coli along with other Gram-positive and Gram-negative bacteria [
25]. The present study focussed on utilizing the lesser concentration of CEA extract from
A. paniculata where 100 μg/ml of the extract proved efficient in controlling the growth and biofilm formation in three different clinical strains and one ATCC strain of
E. coli. 100 μg/ml of CEA extract showed comparable effects as that of the antibiotic in inhibiting the growth of
E. coli strains and moreover, CEA was more effective in inhibiting the biofilm of
E. coli strains compared to the antibiotic. A study conducted by Sule and co-workers reported the antibacterial activity of three different extracts (dichloromethane, methanol, and aqueous) of
A. paniculata against 12 skin infection causing pathogenic bacterial strains. The extracts showed significant effects against all the tested bacterial strains at a concentration of 1000, 500, and 250 μg/disc [
26]. Apart from the antibacterial and antibiofilm activity of CEA extract, molecular docking of 10 different bioactive compounds from
A. paniculata with CTX-M-15 protein revealed a positive docking score. From the docking results, it can be hypothesized that bioactive compounds from
A. paniculata may be a better source for inhibiting the CTX-M protein to control the ESBL producing
E. coli strains. CTX-M beta-lactamases are a growing family of enzymes which are characterized by a selective hydrolysis of ceftriaxone and cefotaxime and more specifically ceftazidime. CTX-M-15 type ESBLs were first reported in
K. pneumoniae,
E. coli and human isolates of
Enterobacter aerogenes from India and Japan. Since that time, CTX-M-15 type ESBLs have been recognized in Enterobacteriaceae strains from various countries like the United Kingdom, Bulgaria, Canada, Russia, Poland, Turkey and France. Extensive research has been conducted on CTX-M-15 type ESBLs in industrialized countries where
E. coli and Klebsiella spp. are the most common cause of urinary tract infections [
27]. In the present study, the molecular docking reports on CTX-M-15 and the bioactive compounds from
A. paniculata are the first to be reported.
ESBL production by
Enterobacteriaceae strains has been a cause of resistance against various antimicrobial agents which in turn presents a hindrance in clinical practice making it difficult to treat infections [
28]. The resistance mechanisms that ESBL strains have developed need to be keenly observed so that novel and effective antimicrobial agents can be discovered and designed properly [
29]. In the present study, the variable expression of a gene encoding CTX-M-15 was observed when treated with CEA extract of
A. paniculata in 3 different ESBL producing strains of
E. coli. The study presented an overview of the CEA extract of
A. paniculata and its strong ability to inhibit the production of ESBL at the molecular level which may act as an alternative to fight the bacterial resistance.
The overall significance of the present study lies in the fact that ESBL producing strains are developing at a fast pace which in turn increases the percentage of antibiotic resistance. In order to stop this increasing menace of antibiotic resistance, a continuous research to find more novel antibacterial agents needs to be carried out. In this study, we presented an approach towards finding a possible way to stop the ESBL producing clinical strains of E. coli and since CTX-M-15 type ESBLs are more prevalent in India and more specifically the southern part, hence the strains positive for CTX-M-15 were chosen for this study. Moreover, the literature about A. paniculata which gives an idea about the overwhelming applications of this very plant in the medicinal field made us choose this plant for the present study.