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Plasmidome in mcr-1 harboring carbapenem-resistant enterobacterales isolates from human in Thailand

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Parichart Boueroy, Thidathip Wongsurawat, Piroon Jenjaroenpun, Peechanika Chopjitt, Rujirat Hatrongjit, Sathaporn Jittapalapong, Anusak Kerdsin

A dangerous form of antibiotic resistance may not need bacteria to reproduce. It can travel in small DNA packages, moving between different bacteria and potentially taking last-resort treatment out of reach.

Abstract

The emergence of the mobile colistin-resistance genes mcr-1 has attracted significant attention worldwide. This study aimed to investigate the genetic features of mcr-1-carrying plasmid among carbapenem-resistant Enterobacterales (CRE) isolates and the potential genetic basis governing transmission. Seventeen mcr-harboring isolates were analyzed based on whole genome sequencing using short-read and long-read platforms. All the mcr-1-carrying isolates could be conjugatively transferred into a recipient Escherichia coli UB1637. Among these 17 isolates, mcr-1 was located on diverse plasmid Inc types, consisting of IncX4 (11/17; 64.7%), IncI2 (4/17; 23.53%), and IncHI/IncN (2/17; 11.76%). Each of these exhibited remarkable similarity in the backbone set that is responsible for plasmid replication, maintenance, and transfer, with differences being in the upstream and downstream regions containing mcr-1. The IncHI/IncN type also carried other resistance genes (blaTEM-1B or blaTEM-135). The mcr-1-harboring IncX4 plasmids were carried in E. coli ST410 (7/11; 63.6%) and ST10 (1/11; 9.1%) and Klebsiella pneumoniae ST15 (1/11; 9.1%), ST336 (1/11; 9.1%), and ST340 (1/11; 9.1%). The IncI2-type plasmid was harbored in E. coli ST3052 (1/4; 25%) and ST1287 (1/4; 25%) and in K. pneumoniae ST336 (2/4; 50%), whereas IncHI/IncN were carried in E. coli ST6721 (1/2; 50%) and new ST (1/2; 50%). The diverse promiscuous plasmids may facilitate the spread of mcr-1 among commensal E. coli or K. pneumoniae strains in patients. These results can provide information for a surveillance system and infection control for dynamic tracing.

Transcript

A dangerous form of antibiotic resistance may not need bacteria to reproduce. It can travel in small DNA packages, moving between different bacteria and potentially taking last-resort treatment out of reach. Drug-resistant gut bacteria are a growing public-health concern because many resist powerful antibiotics through enzymes that break those medicines down.

These resistant bacteria carry enzymes that degrade carbapenem antibiotics, making infections harder to treat when those medicines no longer work. The problem becomes more serious when resistance to a last-resort drug appears in bacteria already resistant to powerful antibiotics, creating strains that could resist nearly every available treatment.

In Thailand, the genetic surroundings of the mcr-1 resistance gene, including its organization in the genome, were still poorly understood. So the study set out to determine complete genomic sequences and compare the plasmids carrying mcr-1 among CRE isolates from human patients in Thailand.

The study found that all seventeen mcr-1-carrying CRE isolates could transfer the resistance gene into E. coli, and concluded that the gene was carried on conjugative plasmids. Here, every resistant isolate could pass the resistance package into another bacterium, showing that the package itself could help move this trait.

The resistance gene was found on three broad kinds of DNA packages. One kind was much more common than the others, while the remaining kinds appeared less often. The common packages were highly similar to one another, but the resistance gene appeared in different positions within some of them.

That suggests a shared transport framework with variation around the cargo. The resistance gene sits within closely matching stretches of DNA across many separate mobile rings, including both short and very large ones.

That shared structure suggests these rings can move the same resistance trait between bacteria and environments. Taken together, the results suggest that the two most common package types carried much of the movement of resistance through these bacteria in Thailand.

So the risk is not only a resistant bacterium spreading. The transferable DNA package may also spread the resistance trait into other bacteria. Most of the common packages formed a related group, and several were close to packages found in bacteria from Thailand, indicating that this package type is circulating there.

Other package types were more closely related to examples from China, suggesting that some may be widely distributed across the region or may share an older source. The resistance problem crosses boundaries: related bacteria and resistance genes have been found in people, animals, and the environment.

Controlling it therefore requires attention to all three. The study advises using antibiotics judiciously as a way to minimize the development and dissemination of colistin resistance in human isolates. In these Thai patient samples, the resistance gene sat on transferable DNA packages that appeared in several bacterial backgrounds.

Tracking those packages, across people, animals, and the environment, matters for protecting treatment.

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