A study by researchers at Washington University School of Medicine in St. Louis suggests that international travelers are bringing home potentially deadly new strains of antimicrobial-resistant superbugs in their gut microbiome. The scientists, together with researchers at Maastricht University, analyzed bacterial communities in the gut microbiomes of 190 Dutch adults before and after a trip to Southeast Asia, South Asia, North Africa and in East Africa, all of which are regions with a high prevalence of resistance genes. . The results confirmed that international travelers typically return home with an unexpected payload of new bacterial strains among the thousands that normally reside in the gut microbiome.
“Even before the COVID-19 pandemic, we knew that international travel was contributing to the rapid increase and spread of antimicrobial resistance globally,” said Alaric D’Souza, medical and research student. PhD at the University of Washington and co-first author of the team’s published research in Genome medicine. “But what’s new here is that we’ve found many completely new genes associated with antimicrobial resistance that suggest a worrying problem on the horizon.” D’Souza and his colleagues describe their findings in an article titled “Destination shapes acquisitions of antibiotic resistance genes, increased abundance and changes in diversity among Dutch travelers. “
Antimicrobial resistance (AMR) is a major global public health threat, with resistant bacteria now rendering antibiotics ineffective and limiting treatment options, the authors wrote. International agencies, including the World Health Organization and the United States Centers for Disease Control and Prevention, have described the rapid spread of antimicrobial resistance as one of the most serious public health threats facing the world is currently facing. “The global spread of AMR threatens decades of success in treating bacterial infections with antibiotics,” the authors noted.
As AMR increases worldwide, there are major geographic differences in the prevalence and type of resistant bacteria and their AMR genes, the team continued. It is an impending medical disaster that could outweigh the chaos created by the COVID-19 pandemic. Low- and middle-income countries generally have a higher burden of endemic AMR than high-income countries. Poverty, lack of sanitation, changing agricultural practices and overuse of antibiotics in humans and livestock have turned many developing regions into hot spots for diseases spread by bacteria, including infections. increasingly resistant to a range of antibiotic treatments.
In addition, “international travel can facilitate the transfer of resistant bacteria and antimicrobial resistance genes from their endemic regions to other places in the world,” the scientists noted. Overcrowding of the population in endemic areas facilitates the spread of these AMR bacteria among residents and travelers in the community, through exposure to contaminated drinking water and food, or to toilets, restaurants, rooms. poorly disinfected hotel and public transport, investigators said. And when people return home from their trips, then they run the risk of transferring these new bacteria to their family, friends and other residents of the community. However, the scientists noted that “returning travelers are rarely tested for resistant bacteria or antimicrobial resistance genes, unless they show clinical symptoms, so the magnitude of the risk of acquiring antimicrobial resistance genes on international travel remains undetermined. “
Traditional genomic techniques look for distinctive genetic signatures of individual pathogens, but may find only known pathogens. In contrast, metagenomic sequencing helps identify all of the organisms present in a given sample, providing new insight into the role of the human microbiome as a reservoir of AMR and how this role might be affected by international travel. “We can sequence all of the extracted DNA using shotgun metagenomic sequencing, and we can directly identify AMR genes in these shotgun metagenomes by mapping the reads to the organized AMR gene database.” , wrote the scientists.
For their new study, the team exploited techniques, including complete metagenomic shotgun sequencing and functional metagenomics, to study the abundance, diversity, function, resistome architecture and context of genes. AMR in the faecal microbiomes of 190 Dutch individuals, before and after travel to various international sites. The fecal samples analyzed for the study were randomly selected from a larger multicenter survey of around 2,000 Dutch travelers, the majority of whom were tourists, known as the COMBAT (Carriage Of Multi-sistant Bacteria After Travel).
The study was designed by lead co-authors John Penders, PhD, medical microbiologist at Maastricht University, and Gautam Dantas, PhD, professor of pathology and immunology at the University of Washington. Manish Boolchandani, PhD, Dantas Lab member during research and 2020 graduate of the university’s doctoral program in Computational and Systems Biology, is also the first author of the article.
Their analyzes detected 121 antimicrobial resistance genes in the gut microbiomes of 190 Dutch travelers. More than 40% of these resistance genes (51 of them) were only discovered using the more sensitive metagenomics technique, suggesting that potentially dangerous genes are not taken into account by the more sensitive approaches. conventional. “While previous studies have scanned travelers’ stool samples for well-known antimicrobial resistant bacteria, we have used a combination of full metagenome sequencing and functional metagenomics to identify known and novel genes that code for the antimicrobial resistance, ”Dantas said.
D’Souza added, “We found significant travel-related increases in the acquisition of resistance genes, abundance and diversity encoded by bacteria endemic to the area visited. These findings strongly support international travel as a vector for the global spread of clinically important antimicrobial resistance genes and underscore the need for broader surveillance of antimicrobial resistant bacteria in the gut microbiome of returning travelers. Interestingly, the team further commented: “… travel-induced gut resistoma shaping was correlated with geographic destination, so people returning to the Netherlands from the same country destination were more likely to have similar resistome characteristics. “
Of particular concern, the study results confirmed that 56 unique antimicrobial resistance genes had become part of the gut microbiome of travelers during their trips abroad, including several high-risk mobile resistance genes, such as as extended spectrum β-lactamases (ESBLs) and the colistin resistance plasmid gene, mcr-1. Beta-lactam resistance is emerging worldwide and confers widespread resistance to treatment with penicillins and other important antibiotics.
The mcr-1 genes protect bacteria from another antimicrobial drug called colistin, which is the treatment of last resort for infections with multidrug-resistant gram-negative bacteria. If colistin resistance spreads to bacteria resistant to other antibiotics, those bacteria could cause truly incurable infections, the CDC warned.
Because metagenomic analysis allows researchers to study all bacteria and genes in a collection of gut microbiome samples as a single large mixed community of organisms, it also provides the opportunity to explore interactions ecological complexities between these organisms.
While bacteria can slowly develop resistance from repeated exposures to antibiotics over time, various bacterial communities also share antimicrobial resistance genes through a faster process called horizontal transfer, usually via the exchange of elements. mobile genetics that allow DNA extracts to jump out of bacteria. to another. “Since the genes that code for resistance to different classes of antibiotics are often located on the same mobile elements, a single horizontal swap has the potential to convert bacteria previously susceptible to antibiotics into a multidrug resistant organism,” Dantas said. .
The researchers also used metagenomic techniques to gather important background information about the location and function of resistance genes. “There was a significant association of resistance genes with mobile genetic elements, a primary means by which resistance genes spread among bacteria,” D’Souza said. “Although our study could not demonstrate that resistance genes are carried by pathogenic bacteria, it is clear that this is possible. Additionally, international travelers have the potential to introduce resistance genes into their own communities when they return home, and future studies directly addressing this possibility are a priority. “
The authors concluded: “Our results demonstrate that international travel is a significant disturbance of the intestinal resistome and reveal specific changes to the destination of traveler’s resistomes, including acquisitions of AMR genes against last-resort antibiotics and colocalization of AMR genes with mobile genetic elements… Interventions to reduce AMR. in low- and middle-income countries with currently high AMR loads may reduce AMR gene acquisitions by travelers.
Dantas added, “The identification of new bacteria and antimicrobial resistant genes could play an important role in slowing the global spread of resistance and guiding potential treatments for related diseases. Our study lays the groundwork for these efforts by providing new insights into the genetic mechanisms underlying the rapid acquisition and sharing of antimicrobial resistance genes in the gut microbiome of people on international travel.