A new study suggests harmless E. coli strains have acquired new genetic material in a wide range of hosts, including poultry and porcine hosts, to emerge as a multi-drug resistant pathogenic strain in humans.

Most E. coli strains inhabit the digestive tracts of mammalian and avian hosts as harmless residents (commensals). When E. coli strains acquire genes that enable them to survive in niches other than the gut in humans, they can cause diseases. Extraintestinal pathogenic E. coli (ExPEC) is the primary cause of urinary tract infections (UTIs) and the second most common cause of neonatal meningitis. It also causes sepsis that kills nearly 11 million people every year.

ST58 is an unusual ExPEC strain that is increasingly responsible for both sporadic and persistent blood infections worldwide. Its proportion in bloodstream infections has more than doubled in the past 12 years, a study conducted on patients in and around Paris shows. In addition to infecting humans, multi-drug resistant ST58 is found in farm animals such as cattle, poultry, swine, as well as in flies, manure, soil, and water.

It is unclear how ST58 emerged as a human pathogen. It is particularly unusual because ST58 belongs to phylogroup B1—one of the eight groups into which E.coli are classified—that is rarely pathogenic.

In a new study published in the journal Nature Communications (“A role for ColV plasmids in the evolution of pathogenic Escherichia coli ST58“), Cameron Reid, PhD, from the University of Technology, Sydney, and his team performed a pan-genomic epidemiological analysis of 752 ST58 strains isolated from humans, animals, and environmental sources worldwide to better understand the evolution and genomic characteristics of this emerging pathogenic strain that is a growing cause of UTIs and sepsis.

“We found that E. coli ST58 from pigs, cattle, and chickens contain pieces of genetic material called ColV plasmids, which are characteristic of this strain of disease-causing E. coli,” said Reid. ColV plasmids—circular double-stranded DNA molecules that replicate independent of the bacterial chromosome—are highly prevalent in avian pathogenic E. coli (APEC) and cause colisepticemia in birds. Acquiring ColV plasmids can prime harmless strains of E. coli to cause extra-intestinal infections in humans and increase its antimicrobial resistance.

“Zoonosis, particularly in relation to E. coli, should not be viewed simply as the transfer of a pathogen from an animal to a human,” said Steven Djordjevic, PhD, professor of infectious disease, group leader in the iThree Institute at the University of Technology, Sydney, and senior author of the study. “Rather, it should be understood as a complex phenomenon arising from a vast network of interactions between groups of E. coli and other bacteria, and the selective pressures they encounter in both humans and animals.”

The authors noted that their results indicate that acquiring ColV plasmids and non-human sources such as cattle, chickens, and pigs, has played a role in the evolution of ST58 as a human pathogen. “The contribution of non-human sources to infectious disease in humans is typically poorly understood and its potential importance under-appreciated, as the debate regarding the ecological origins of the SARS-CoV2 virus attests,” said Reid.

The study has broad implications for public health policy that spans across the food industry, and veterinary and clinical settings. “In a globalized world, eminently susceptible to rapid dissemination of pathogens, the importance of pro-active management of microbial threats to public health cannot be understated,” said Reid. “To date, infectious disease public health has been a reactive discipline, where action can only be taken after a pathogen has emerged and done some damage.”

Reid hopes genome sequencing technology will enable public health policy to take a more proactive stance on infectious diseases by predicting the emergence of pathogens through genome surveillance and the implementation of preventive interventions. Reid said, this requires ongoing research and collaborations with government, public health bodies, food producers, and clinicians, and would involve surveillance of non-human sources of microbes.

“This would include domestic and wild animals—particularly birds—food products, sewerage, and waterways, in what is referred to as a ‘One Health’ approach. Some microbes, like ST58 E. coli, know very few barriers between these increasingly interconnected hosts and environments,” said Reid.

The authors reinforced that pathogen emergence should be understood within a One Health framework, where pathogen evolution is analyzed in the context of complex mechanistic drivers and interactions between environments and hosts rather than historically ineffective human-centric approaches.