Genomics surveillance in One Health

As we have seen in the previous step, a One Health approach involves connecting several disciplines and sectors, acknowledging that health is connected: the health of people is closely connected to the health of animals and to the environment. Here we will focus on some examples from Colombia to show genomic surveillance using a One Health approach.

In the past decade, a pilot of the programme ‘Integrated Surveillance of Antimicrobial Resistance’ in Colombia monitored Antimicrobial resistance (AMR) in the poultry chain. Traditional microbiology tools have shown that Salmonella spp. and E. coli isolates had a remarkably high antimicrobial resistance to ampicillin, cephalosporins and ciprofloxacin. Subsequent whole-genome sequencing (WGS) of Salmonella isolates from broilers and layers allowed in silico prediction of serovars using SISTR (a bioinformatics platform used for performing analyses on draft Salmonella genome assemblies). WGS enabled the detection of AMR genes in different families of antibiotics as aminoglycosides, β-Lactamics, quinolones, streptothricin, sulfonamides and tetracyclines 80% of the isolates were predicted to have multidrug resistance. In line with the widespread presence of resistance to quinolones (ciprofloxacin), genotypic analysis of ciprofloxacin-resistant isolates identified 21 harbouring various resistance genes.

Klebsiella pneumoniae is a pathogen that causes community and hospital-acquired infections. Carbapenem-resistant K.pneumoniae (CRKP) causes untreatable infections and high mortality. In Colombia, K. pneumoniae is the most frequent pathogen found in intensive care units, with resistance to carbapenems reported in up to 15.6% of isolates. The CRKP clones associated with KPC-type carbapenemases most commonly reported in Colombia are CG258, CG307, and CG14/15. Colombia’s National Reference Laboratory explored CRKP epidemiology by sequencing 425 CRKP isolates from the 21 most-populated departments in the country. From the sequenced isolates, 91.5% were carbapenemase-producing strains (carrying blaKPC-3, blaKPC-2, NDM-1, blaNDM-9, blaVIM-2, blaVIM-4, and blaVIM-24 encoding carbapenemase genes). These data support a recent expansion and the endemicity of CRKP with the circulation of 7 high-risk clones, the most frequent being CG258 (48.39% of isolates).

Genomic surveillance outlines the complex epidemiology of CRKP in Colombia. CG258 expanded clonally and carries specific carbapenemases in specific mobile genetic elements, while the other previously identified high-risk clones (CG147, CG307, and CG152) present a more diverse complement of carbapenemases. This example stresses the importance of WGS-based surveillance to monitor evolutionary trends of sequence types, mobile genetic elements, and resistance and virulence genes.

There is an increasing occurrence of multidrug-resistant bacteria with extended-spectrum β-lactamases (ESBLs) and/or plasmid-encoded AmpC (pAmpC) β-lactamases in clinical and environmental settings across the world. Samples from broiler farms, slaughterhouses, and retail stores were analysed to determine the prevalence and resistant profiles of Salmonella enterica in the Colombian poultry chain. WGS of these strains enabled the diversity of ESBL/pAmpC genes in extended-spectrum cephalosporin-resistant Salmonella enterica genes to be determined and the phylogeny of ESBL/pAmpC-carrying Salmonella to be constructed.

WGS enabled Salmonella isolates to be compared locally, focusing on the resistance mechanisms involved in cephalosporin resistance and the genetic relatedness between the poultry chain production stages. Also, the WGS data generated allowed researchers to compare local data with global Salmonella genomic data to understand the regional dissemination of this pathogen (see Figure 1). The resistance was mainly encoded by blaCMY−2 and blaCTX−M−165 genes on IncI1/ST12 and IncQ1 plasmids. The clonal expansion of ESBL/pAmpC mechanisms on IncI1 plasmids in two sub-clusters across the poultry chain supply showed there is a high diversity in Colombia. The long evolutionary distance with Salmonella from other countries suggests there was local dissemination of the extended-spectrum cephalosporin-resistant Salmonella enterica in Colombia. These findings alerted the Colombian food safety systems and the government.

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Figure 1 – Geographical distribution of the 260 extended-spectrum cephalosporin-resistant Salmonella enterica in Colombia sampled between 2008 and 2013. Source: Frontiers in Microbiology

In summary, WGS approaches in Colombia:

• Improved the understanding of the dissemination risks of AMR bacteria in the One Health Continuum.
• Enabled the identification of genes that are predictive of resistance to multiple families of antibiotics in a single analysis. At the same time, detecting several virulence factors facilitated the study of the pathogenesis of different infections.
• Advanced massive characterization complements the approaches required in surveillance and epidemiologic AMR investigations.
• Are essential tools for outbreak investigation. However, efforts must be coordinated nationally to achieve a more significant impact.

Furthermore, metagenomic technologies using short and long-read next-generation sequencing data analyses help determine the local AMR gene diversity, abundance, and variations of bacterial pathogens. These monitoring tools could be strategic in AMR surveillance and investigation under the One Health approach. The results could be the basis for creating new policies.