Plugging the leaks: antibiotic resistance at human-animal interfaces in low-resource settings

Abstract

Antibiotic resistance is one of the greatest public health challenges of our time. International efforts to curb resistance have largely focused on drug development and limiting unnecessary antibiotic use. However, in areas where water, sanitation, and hygiene infrastructure is lacking, we propose that bacterial flow between humans and animals can exacerbate the emergence and spread of resistant pathogens. Here, we describe the consequences of poor environmental controls by comparing mobile resistance elements among Escherichia coli recovered from humans and meat in Cambodia, a middle-income country with substantial human-animal connectivity and unregulated antibiotic use. We identified identical mobile resistance elements and a conserved transposon region that were widely dispersed in both humans and animals, a phenomenon rarely observed in high-income settings. Our findings indicate that plugging leaks at human-animal interfaces should be a critical part of addressing antibiotic resistance in low- and especially middle-income countries.

Figure 1.

Unchecked environmental leaks and antibiotic use create myriad opportunities for the exchange of bacteria and mobile resistance elements among humans and animals. Potential transmission pathways include (1) inadequate sewage treatment infrastructure leads to contamination of human and animal drinking water; (2) animal waste contaminates drinking water; (3) raising many animals in confinement propagates disease; (4) raw sewage fertilizing crops for human consumption; (5) open defecation leads to fecal–oral transmission among humans and animals; (6) contact with animal waste; (7) farmed fish are fed pig and poultry feces; (8) consumption of undercooked chicken and fish; (9) pests contaminate food preparation areas; (10) meat contaminated by feces during processing; (11) multiple species in contact in unhygienic conditions; and (12) poor hygiene in markets. Layout stylized to indicate connectivity. Asterisks indicate antibiotic inputs.

Figure 2.

Frequent mixing of human- and animal-adapted microbes creates opportunities for the exchange of antibiotic resistance at multiple scales (ie of bacteria, plasmids, and transposable elements).

Figure 3.

High antibiotic use and environmental leakiness is associated with the mobilization of an extended-spectrum β-lactamase (ESBL)-encoding transposon region across different bacterial lineages and hosts in Cambodia. (a) Sankey diagram depicting the flow of ESBL genes among Escherichia coli from human and animal origin. ESBL genes flow freely among human and animal-origin E coli in the leaky Cambodian ecosystem but are largely isolated to specific hosts in the less leaky UK ecosystem. (b) Core-genome phylogenetic tree depicting diverse ESBL-encoding E coli lineages circulating in Cambodia. A bla_CTX-M-encoding transposon region has been acquired by multiple E coli sub-lineages from humans and meat, underscoring rampant genetic exchange in a highly leaky system with substantial antibiotic selective pressure. Tree is mid-point rooted and scale indicates substitutions per site.