Development of Novel Antimicrobials to Counter Drug-Resistant Bacteria
Advancements in technology and modern medicine have made it possible for humans to live longer and at a higher quality of life. This is possible in part due to the discovery of potent antimicrobial drugs. These drugs work by killing or inhibiting the growth of microorganisms. However, widespread use of these drugs renders them useless as, over time, microbes can gain resistance. As such, the number of effective antimicrobials is dwindling.
A leading cause of antimicrobial resistance is agriculture. Livestock are fed a wide array of antibiotics to prevent them from getting sick and allow them to grow faster. However, overuse causes microbes like bacteria to gain resistance. This resistance, coupled with the crowded living conditions in farms, allows microbes to transmit this trait to one another quickly. As such, farms can be reserves of antibiotic resistant microbes, leading to outbreaks like the avian flu. However, researchers at the Public Library of Science, Betts et al., discovered a compound that increases the efficacy of antibiotics against antibiotic-resistant strains of avian E. coli.
A leading cause of antimicrobial resistance is agriculture. Livestock are fed a wide array of antibiotics to prevent them from getting sick and allow them to grow faster. However, overuse causes microbes like bacteria to gain resistance. This resistance, coupled with the crowded living conditions in farms, allows microbes to transmit this trait to one another quickly. As such, farms can be reserves of antibiotic resistant microbes, leading to outbreaks like the avian flu. However, researchers at the Public Library of Science, Betts et al., discovered a compound that increases the efficacy of antibiotics against antibiotic-resistant strains of avian E. coli.
A scientist performing a protein assay, useful in determining qualitative or quantitative assessments.
Image Source: DarkoStojanovic
The researchers began by isolating avian strains of E. coli from poultry farms. In order to test for resistance, they treated the isolated strains with 24 commonly used antibiotics. Those that were immune to 5 classes or higher were selected to determine the minimum inhibitory concentrations (MIC) of colistin and a manganese carbonyl complex. Increasing concentrations of colistin and the manganese carbonyl complex were injected along with the drug into resistant larval strains. Finally, they determined the microbe count in each of the larvae.
Researchers found that the manganese carbonyl complex produced relatively high MICs. This meant that a high dose of the compound was necessary to achieve inhibition of the bacteria. With the addition of colistin, however, the MIC drastically dropped two orders of magnitude. As such, this combination produced superior bacteria killing and larval survival compared to either drug alone. Researchers attribute this synergistic effect to colistin’s property as a permeabilizing agent, which allows the manganese carbonyl complex to breach and penetrate the membrane of the bacteria, disrupting important cellular processes.
These discoveries have several important implications. The researchers stated that their study was the first to examine in vivo antibacterial activity of the manganese carbonyl complex. As such, further studies involving the compound should be tested against other important human and animal pathogens, such as Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. All of these pathogens are common carriers of antibiotic resistance genes and are associated with serious infections. Thus, the compound could have potential for future applications in medicine and lay the groundwork for other solutions to drug-resistant microbes.
Researchers found that the manganese carbonyl complex produced relatively high MICs. This meant that a high dose of the compound was necessary to achieve inhibition of the bacteria. With the addition of colistin, however, the MIC drastically dropped two orders of magnitude. As such, this combination produced superior bacteria killing and larval survival compared to either drug alone. Researchers attribute this synergistic effect to colistin’s property as a permeabilizing agent, which allows the manganese carbonyl complex to breach and penetrate the membrane of the bacteria, disrupting important cellular processes.
These discoveries have several important implications. The researchers stated that their study was the first to examine in vivo antibacterial activity of the manganese carbonyl complex. As such, further studies involving the compound should be tested against other important human and animal pathogens, such as Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. All of these pathogens are common carriers of antibiotic resistance genes and are associated with serious infections. Thus, the compound could have potential for future applications in medicine and lay the groundwork for other solutions to drug-resistant microbes.
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