Antibiotic resistance is one of the biggest threats to global health, food security, and development today. A new study shows how superbugs adapt to combat 'last-resort antibiotics'. Researchers at Rice University and the University of Texas Health Science Center conducted experiments to determine how these antibiotic-resistant bacteria adapt to battle last-resort antibiotics, hoping to find clues that can someday prolong or impvove drug efficacy.
Vancomycin-resistant Enterococci, as imaged with a scanning electron microscope. (Photo by Janice Haney Carr/CDC)
The study, which was published in the journal Antimicrobial Agents and Chemotherapy, tracked the biochemical changes of vancomycin-resistant Enterococci (VRE) and it adapts to combat another type of antibiotic, daptomycin.
"We need to get to a stage where we can anticipate how these pathogens will become resistant to antibiotics so we can stay one step ahead of them," Yousif Shamoo, Rice biochemist and co-author of the study, said.
Antibiotic-resistant bugs on the rise
Antibiotic resistance leads to higher medical costs, prolonged hospital stays, and increased mortality. It can affect people of all ages and in many countries. One of the culprits of antibiotic resistance is the misuse of antibiotics.
The World Health Organization (WHO) reports that in 2014, antibiotic-resistant infections were on pace to kill 10 million people each year across the globe by 2050. The WHO Global Antimicrobial Surveillance System (GLASS) shows the widespread incidence of antibiotic resistance in 500,000 people with suspected bacterial infections in 22 countries. The most common bacteria that are resistant include Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Salmonella spp.
The Centers for Disease Control and Prevention (CDC) reports that VRE is one of the country’s leading antibiotic resistance threats. It estimates that about 20,000 individuals in the United States will be infected with VRE this year, and will kill approximately 1,300 people.
Last resort drugs for infections
Doctors usually use daptomycin, one of the last resort drugs used to fight multi-drug resistant bacteria such as VRE, glycopeptide-resistant enterococci, and Methicillin-Resistant Staphylococcus aureus (MRSA).
Medical officials documented some cases of daptomycin resistance in 2005, and the number is still increasing across the globe.
What the researchers found
The researchers said that one of the main findings of the study is that Enterococcus faecium, a strain of VRE, has varied techniques for the resistance to antibiotics. The diversity can make it hard for doctors to treat the infection.
They found that daptomycin binds to bacterial cell membranes and alters important cell processes, causing cell death. The bacteria respond to the antibiotic by changing their cell envelopes to reduce antibiotic binding to the membrane or diverting the binding away.
Moreover, they found that multi-drug resistant Enterococcus faecium contains alleles linked to the activation of the three-component cell-envelope-stress-response system or LiaFSR signaling pathway.
“Our findings indicate that E. faecium can evolve diverse evolutionary trajectories to daptomycin resistance that are shaped by the environment to produce a combination of resistance strategies,” the researchers concluded in the study.
“The accessibility of multiple and different biochemical pathways simultaneously suggests that the outcome of daptomycin exposure results in a polymorphic population of resistant phenotypes making E. faecium a recalcitrant nosocomial pathogen,” they added.
The research sheds light on better treatment strategies or new “co-drugs” that can target the bacteria’s ability to become resistant. Co-drugs help fight resistance by being given with antibiotics such as daptomycin to help patients battle infection and prevent the spread of hard-to-curb bacteria strains in hospitals.
One of the researchers, Dr. Amy Prater, showed that the same strain of VRE could activate various biochemical pathways to trigger up to three strategies. The strategy can make it harder for doctors to curb the growing incidence of daptomycin resistance in patients with VRE.
Environment Shapes the Accessible Daptomycin Resistance Mechanisms in Enterococcus faecium, Amy G. Prater, Heer H. Mehta, Abigael J. Kosgei, William R. Miller, Truc T. Tran, Cesar A. Arias, Yousif Shamoo, DOI: 10.1128/AAC.00790-1, https://aac.asm.org/content/early/2019/07/16/AAC.00790-19