Researchers have found a gene that gives Salmonella resistance to antibiotics


Researchers from North Carolina State University have found a gene that gives Salmonella resistance to antibiotics of last resort in a sample taken from a human patient in the U.S.

The find is the first evidence that the gene mcr-3.1 has made its way into the U.S. from Asia.

There are more than 2,500 known serotypes of Salmonella.

In the U.S., Salmonella enterica 4,[5],12:i:- ST34 is responsible for a significant percentage of human illnesses.

The drug resistance gene in question – known as mcr-3.1 – gives Salmonella resistance to colistin, the drug of last resort for treating infections caused by multidrug-resistant Salmonella.

“Public health officials have known about this gene for some time,” says Siddhartha Thakur, professor and director of global health at NC State and corresponding author of the research.

“In 2015, they saw that mcr-3.1 had moved from a chromosome to a plasmid in China, which paves the way for the gene to be transmitted between organisms.

For example, E. coli and Salmonella are in the same family, so once the gene is on a plasmid, that plasmid could move between the bacteria and they could transmit this gene to each other.

Once mcr-3.1 jumped to the plasmid, it spread to 30 different countries, although not—as far as we knew—to the U.S.”

Thakur’s lab is one of several nationally participating in epidemiological surveillance for resistant strains of Salmonella.

The lab generates whole genome sequences from Salmonella samples every year as part of routine monitoring for the presence of antimicrobial-resistant bacteria.

When veterinary medicine student Valerie Nelson and Ph.D. student Daniel Monte did genome sequencing on 100 clinical human stool samples taken from the southeastern U.S. between 2014 and 2016, they discovered that one sample contained the resistant mcr-3.1 gene.

The sample came from a person who had traveled to China two weeks prior to becoming ill with a Salmonella infection.

“This project proved the importance of ongoing sequencing and surveillance,” says Nelson. “The original project did not involve this gene at all.”

“The positive sample was from 2014, so this discovery definitely has implications for the spread of colistin-resistant Salmonella in the U.S.,” Thakur says. “Our lab will continue to try and fill in these knowledge gaps.”

The research appears in the Journal of Medical Microbiology and was supported by the National Institutes of Health/Food and Drug Administration (award number 5U 18FD006194-02).

Monte and Nelson are first author and co-author, respectively. Prior to his global health role, Thakur was associate director of the emerging infectious diseases program at NC State’s Comparative Medicine Institute.

Bacterial drug resistance is an ongoing severe public health problem.

This issue concerns not only the bacteria causing nosocomial infections but also the pathogenic and non-pathogenic bacteria that spread in the community.

Antibiotics use in hospitals and farms has caused the increasing emergence of multi-drug resistant (MDR, defined as resistant to more than three kinds of antibiotics) and pan-resistant strains, while global trade and travel contribute to their worldwide spread [1].

Additionally, there are fundamental driving forces that aggravate the spread of antibiotic resistance, including the competitive advantage for antibiotic-resistant bacteria under antibiotic pressure and the active horizontal transfer of antibiotic resistance gene-harbouring plasmids among bacteria [2].

In 2016, a plasmid encoding mcr-1-mediated polymyxin resistance in Enterobacteriaceae was newly recognized; its existence presents a severe threat in the global confrontation with antibiotic resistance [3].

MCR-1, coded by the mcr-1 gene, is predicted to be an integral membrane protein with the catalytic activity of phosphoethanolamine transferases [4] that modifies the chemical structure of lipid A via the addition of phosphoethanolamine, resulting in a reduction in the binding affinity of lipopolysaccharide (LPS) to colistin [[3], [4], [5]].

Polymyxins are used as the last resort antibiotics for clinical infections caused by MDR Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae [6]; however, colistin use in the farming sector has promoted the selection and transmission of mcr-1 and mcr-like gene-mediated drug-resistant strains [7]. mcr-1-positive plasmids can also carry other antibiotic resistance genes, notably ESBL genes; this can generate resistance to multiple drugs and contribute to the spread of MDR bacteria in human populations [8].

Among the reported bacteria with mcr-1-mediated colistin resistance, most were isolated from animal sources, whereas only a few were isolated from hospital patients with nosocomial infections [9,10]; this uneven distribution is likely due to the asymmetric polymyxin use in these two sectors. Healthy carriers of these bacteria have also been reported [11].

Epidemiological investigations found that most mcr-1-harbouring plasmids appeared to be restricted to two Enterobacteriaceae species (Escherichia coli and Klebsiella pneumoniae). However, mcr-1-harbouring Salmonella have been detected from animals, food, and patients in Europe [12], as well as from swine, poultry, and carriers in China [11,13].

Salmonella are a common concern in food safety, as their frequent transmission from agricultural animals and food to humans causes numerous gastroenteritis cases, and these pathogens are responsible for >600,000 deaths annually [14].

Surveillance in the United States showed that non-typhoid Salmonella infections have been the leading cause of death among foodborne bacterial pathogens, with the highest incidence among children aged <5 years old (69.5 infections per 100,000 children) [15,16]. Furthermore, MDR Salmonella, which are important agents in the transmission of antibiotic resistance genes, have become a severe problem in the animal breeding sector as well as a medical threat to people [17,18].

To estimate the trend and threat of colistin resistance mediated by plasmids in community-acquired Salmonella infections, a population- or outpatient-based continuous epidemiological surveillance is necessary. In Shanghai Municipality in China, a laboratory surveillance project on Salmonella infection has been underway since 2006. Here, we conducted a retrospective study to determine the prevalence of mcr-1-positive Salmonella in community-acquired infections and to ascertain the molecular characteristics of the epidemic mcr-1-harbouring strains.

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More information: Daniel F. Monte et al, Multidrug- and colistin-resistant Salmonella enterica 4,[5],12:i:- sequence type 34 carrying the mcr-3.1 gene on the IncHI2 plasmid recovered from a human, Journal of Medical Microbiology (2019). DOI: 10.1099/jmm.0.001012

Journal information: Journal of Medical Microbiology
Provided by North Carolina State University


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