Bacteria Evolve Antimicrobial Resistance More Rapidly in Diabetes Model
Antibiotic-resistant strains of Staphylococcus aureus flourish in a diabetic infection environment.
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Antimicrobial resistance (AMR), which arises when bacteria, viruses, fungi and parasites evolve resistance to medicines, is a top global public health threat. New findings from University of North Carolina (UNC) researchers show that a diabetic infection environment can drive the evolution of antibiotic resistance, contributing to the global AMR crisis.
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Subscribe for FREEInvestigating Staphylococcus aureus (S. aureus) – a leading cause of antibiotic resistance-associated infections and deaths – the researchers determined that the bacterium evolves AMR rapidly in diabetic mice. Published in the journal Science Advances, this result highlights the importance of controlling blood sugar levels in diabetes models (through the administration of insulin) to reduce the chances of antibiotic-resistant mutations arising.
Diabetic infections drive the emergence of AMR
There are nearly 530 million people worldwide with diabetes mellitus, a chronic condition that impacts the body’s ability to control blood sugar and fight off infection. S. aureus is the most common bacteria associated with diabetic infections.
Given that the diabetic environment supports more invasive and severe infections, resulting in the increased usage of antibiotics, the UNC researchers set out to determine whether S. aureus would evolve AMR more rapidly in this environment.
To investigate, the researchers infected both diabetic and non-diabetic mouse models with S. aureus and treated them with the antibiotic rifampicin. After just four days, the bacteria had evolved to become resistant to rifampicin in the diabetic mouse model, with the mutation taking over the entire infection. No rifampicin-resistant bacteria were observed in the non-diabetic models.
When the diabetic and non-diabetic models were inoculated with S. aureus as before but supplemented with rifampicin-resistant bacteria, the bacteria rapidly took over the diabetic infection. However, the resistant bacteria remained only a sub-population in the non-diabetic model after four days of antibiotic treatment.
Deadly bacteria feed off excess glucose
Diabetes alters the body's ability to control glucose, which can result in a buildup of excess glucose in the bloodstream. In addition, the condition has been shown to impair the immune system’s ability to control infection. These factors taken together make the diabetic environment ripe for the emergence of antibiotic-resistant bacteria.
“The lack of innate immune control and excess glucose availability lead to unrestricted growth of the pathogen,” Dr. Brian Conlon, associate professor at UNC, told Technology Networks. “The large numbers of bacteria increase the likelihood of resistance mutations occurring and importantly, once a resistant mutant is present, the excess glucose allows it to rapidly outgrow and take over the infection, whereas the same resistant mutant remains fairly well restricted in a non-diabetic background.”
S. aureus is uniquely positioned to take advantage of the diabetic environment. “S. aureus has four dedicated glucose transporters, two of which are unique to S. aureus,” said Conlon. “It is well adapted to utilize the excess glucose available in the diabetic infection environment. Furthermore, its virulence factors are upregulated in the high glucose environment.”
Given the increasing prevalence of diabetes and AMR worldwide, these findings emphasize the importance of preventing diabetic infections. “This work highlights another negative outcome associated with uncontrolled glucose, as indeed insulin was able to stop resistance from taking over,” explained Conlon.
“This may have more implications for the treatment of infection in diabetics, particularly patients with difficult-to-control blood sugar. In these instances, using multiple antibiotics may be advisable to restrict the evolution of resistance,” said Conlon.
The researchers hope to expand their efforts to understand the link between diabetes and AMR, with Conlon stating that, “Plans are underway to examine if the same phenomenon we’ve observed in mice is also occurring in patients.”
As well as studying other antibiotic-resistant bacteria of interest, such as Enterococcus faecalis, Pseudomonas aeruginosa and Streptococcus pyogenes, the researchers plan to study other conditions where AMR could thrive.
“We would also like to branch out to examine the evolution of resistance in patients with other conditions that will impact immune function, such as patients undergoing chemotherapy or transplant patients,” Conlon concluded.
Reference: Shook JC, Genito CJ, Darwitz BP, et al. Diabetes potentiates the emergence and expansion of antibiotic resistance. Sci Adv. 11(7):eads1591. doi: 10.1126/sciadv.ads1591
About the interviewee
Dr. Brian Conlon is an associate professor at the University of North Carolina (UNC) Chapel Hill. Conlon is an Irish microbiologist and earned a BSc at the University of Galway before completing a PhD at University College Dublin. He did his postdoctoral training under Dr. Kim Lewis at Northeastern University before starting his own lab at UNC Chapel Hill in 2016. Conlon is deeply committed to developing a better understanding of how antibiotics work in the infection microenvironment and using the resulting knowledge to develop new therapeutic strategies to improve antibiotic efficacy and curb the development and spread of antibiotic resistance. Conlon is currently PI on multiple awards from NIAID and is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease.
