The Power of Two: How Plant Extracts Can Supercharge Antibiotics

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The Power of Two: How Plant Extracts Can Supercharge Antibiotics

Introduction

The rise of antibiotic-resistant “superbugs” is one of the greatest threats to global health. As conventional drugs lose their power, scientists are searching for innovative ways to fight back. One of the most exciting strategies is combination therapy, where the effectiveness of existing antibiotics is amplified by natural compounds.

This excerpt from Dr. Abdul Haq’s research delves into the fascinating world of synergistic antimicrobial activity, exploring how extracts from the Jatropha curcas plant can work together with commercial antibiotics. It reveals how these natural partners can overcome bacterial defenses, making even resistant strains vulnerable once again and paving the way for a new generation of more potent medicines.

Excerpt

“Combinatorial therapy or synergistic interaction is recommended as an effective strategy to help resolve the issue of antibiotic resistance, cellular toxicity and long-term treatments of the available antibiotics. It can also add to find broad-spectrum antibiotics compared to monotherapies (Marr et al. 2004). In the current study, antibiotics were combined with potent bioactive compounds of the J. curcas, aiming to increase their antibacterial potential, overcome resistance and reduce the cost and duration of antimicrobial therapy.

When evaluated in combination with J. curcas extracts or seed oil, the activity of the selected antibiotics increased (MICs range of 0.097 to 100 mg/mL) as compared to the activity of J. curcas extracts or seed oil when screened alone (MIC range of 50 to 200 mg/mL).

Individually, methanolic extract remained the most active (MIC 50 mg/mL) amongst the de-oiled seed extracts against various methicillin resistant S. aureus (MRSA1, MRSA2 and MRSA3) strains. The MIC value of the plant extract below 0.1 mg/mL is considered significant, moderate below or equal to 0.625 mg/mL and weak above 0.625 mg/mL (Kuete 2010). Individually, cefotaxime was the most potent (MIC 0.19 µg/mL) against clinical isolates, A. baumannii and P. vulgaris.

Methanolic or n-hexane extracts in combination with ofloxacin or ciprofloxacin against E. coli (ATCC25922) or S. aureus (ATCC25923) exhibited the highest antibacterial activity (MIC 0.097 mg/mL), respectively. Moreover, in combination with seed oil and n-hexane extract, ciprofloxacin exhibited highest activity against S. aureus ATCC25923 (MIC 0.045 µg/mL). Ofloxacin in combination with seed oil or methanolic extract and ciprofloxacin with seed oil exhibited a similar activity (MIC 0.049 µg/mL) against E. coli ATCC25922 strain, while rifampicin with all extracts exhibited high activity (MIC 0.097 µg/mL) against A. baumannii MDR and MRSA3 strains.

The antibiotic/extracts combinations screened as antibacterial agents in this study, were also studied to evaluate their synergistic, indifferent, additive or antagonistic effect that occurs when the antibacterial activity of the drug combination exceeds the sum of the individual drug activities, the activity of both drugs (in combination or individually) remains equal, there is no obvious change in the activity of both drugs (in combination or individually) or the activity of one drug is reduced in the presence of other, respectively. (Borisy et al. 2003; Branen and Davidson 2004).

In combinations, methanolic extract and rifampicin exhibited synergistic rates of 15.29% against selected pathogenic strains. These treatments exhibited the highest synergistic activities against A. baumannii, E. coli, E. faecalis, S. aureus, and P. aeruginosa, methicillin resistant S. aureus (MRSA2, MRSA3, MRSA4 and MRSA5), A. baumannii (MDR strain), P. chlororaphis, E. coli ATCC25922 and S. aureus ATCC25923 (Table 3.1 and 3.5).

Earlier studies have reported strong synergism between rifampicin and other antimicrobial agents (Timurkaynak et al. 2006). This makes rifampicin a strong candidate for combination antimicrobial therapies. Among all the strains, E. coli ATCC25922 was the most susceptible to extracts (methanolic, n-hexane and seed oil) in combination with four commercial antibiotics (rifampicin, ciprofloxacin, cefotaxime and ofloxacin). Among antibiotics, highest antagonistic effects were shown by moxifloxacin in combination with all extracts with the only exception of synergistic activities with methanolic extract against A. baumannii and S. aureus strains.

Aqueous extract was least active in combinatorial treatments and exhibited no synergistic activities against E. coli, E. faecalis, P. vulgaris and S. aureus. Aqueous extracts are known to exhibit relatively lower antibacterial activities compared to methanolic or n-hexane extract (Matu and Van Staden 2003). The present study found that extracts were more potent in combination than they were individually, against selected MDR strains. It is suggested that plant extracts hypothetically increase the efficacy of antibiotics against MDR strains and inhibit their efflux pumps or change resistance properties by releasing their antimicrobial compounds (Stermitz et al. 2000).

In combination treatments, seed oil was the least active against MDRs and exhibited synergism only in combination with ofloxacin against MRSA1. The seed oil did not exhibit any combined effect against remaining MDR strains. The possible reason may be the instability of long chain fatty acids (Loftsson et al. 2016), or their tendency to bind non-specifically to proteins and other target compounds (Desbois and Smith 2010). Against MDR strains, moxifloxacin exhibited highest antagonism in combination with extracts and seed oil. However, seed oil exhibited higher synergism compared to the aqueous extract against clinical and reference strains. Literature has reported strong antimicrobial activity of oils (Thormar 2010).

The selected plant extracts and oil exhibited strong synergism with nucleic acids targeting antibiotics such as rifampicin, ofloxacin and ciprofloxacin. Rifampicin targets the DNA-dependent RNA polymerase inhibiting DNA-dependent RNA synthesis. Ofloxacin and ciprofloxacin mainly target DNA gyrase enzymes and inhibit bacterial cell division (Bébéar et al. 1998). There could be some possible reasons for this. Firstly, this strong synergism could be the result of interaction of the extracts and oil with outer membrane, cell wall and cell membrane and of antibiotics to nucleic acids. This suggests that the extracts/oil target outer membranes allowing antibiotics to enter the cells, inhibiting nucleic acids machinery thus inhibiting cell division or apoptosis.

Secondly, the two compounds used in combination form a new bioactive compound which has stronger antimicrobial effects. (Vaara 1992). Thirdly, the phytochemicals present in J. curcas extracts may reduce inherited bacterial resistance. For instance, flavonoids and polyphenols; methanolic extract combined with antibiotics may have altered bacterial resistance thereby increasing combination treatment efficacy (Olajuyigbe and Afolayan 2012). Cefotaxime, a cell wall inhibitor, binds to penicillin-binding proteins inhibiting peptidoglycan synthesis. The present study has found relatively lower synergism exhibited by cefotaxime with extracts and oil. Moxifloxacin was an exception; although it is a broad-spectrum DNA gyrase inhibiting antibiotic but in the present study, it exhibited antagonism in most of the interactions.

Further study is required to elucidate structural changes in compounds during interactions. Cefotaxime, a cell wall inhibitor, exhibited potent activities in combination with extracts and oil, indicating enhancement in its antibacterial potential. A study by (Zhao et al. 2001) strengthens this claim, stating that cell wall targeting antibiotics exhibit increased activity when combined with phytochemicals targeting the same site. Moreover, efflux pump, an important tool for microbial resistance to antibiotics, is also affected by combination of antibiotics and phytochemicals. (Coutinho et al. 2008). In view of the previous combination therapy studies, it is held that phytochemicals from J. curcas seed oil and de-oiled seed extracts combined with some antibiotics can make human pathogenic clinical bacterial and MDR strains more sensitive.”

Source Citation

• Researcher’s full name: Abdul Haq
• Title: Biotechnological Applications of Jatropha curcas Seeds for Bioenergy Carriers and Bioactive Compounds
• Guide(s): Dr. Malik Badshah
• University: Quaid-i-Azam University, Islamabad
• Completed Date: 2020
• Excerpt Page Numbers: 75, 76, 77