Transmission of antimicrobial resistance in the gut microbiome of gregarious cockroaches: the importance of interaction between antibiotic exposed and non-exposed populations

Abstract

Antimicrobial resistance (AMR) is a major global health concern, further complicated by its spread via the microbiome bacterial members. While mathematical models discuss AMR transmission through the symbiotic microbiome, experimental studies are scarce. Herein, we used a gregarious cockroach, Pycnoscelus surinamensis, as an in vivo animal model for AMR transmission investigations. We explored whether the effect of antimicrobial treatment is detectable with metagenomic sequencing, and whether AMR genes can be spread and established in unchallenged (not treated with antibiotics) individuals following contact with treated donors, and under various frequencies of interaction. Gut and soil substrate microbiomes were investigated by metagenomic sequencing for bacterial community composition and resistome profiling. We found that tetracycline treatment altered the treated gut microbiome by decreasing bacterial diversity and increasing the abundance of tetracycline resistance genes. Untreated cockroaches that interacted with treated donors also had elevated tetracycline resistance. The levels of resistance differed depending on the magnitude and frequency of donor transfer. Additionally, treated donors showed signs of microbiome recovery due to their interaction with the untreated ones. Similar patterns were also recorded in the soil substrate microbiomes. Our results shed light on how interacting microbiomes facilitate AMR gene transmission to previously unchallenged hosts, a dynamic influenced by the interaction frequencies, using an in vivo model to validate theoretical AMR transmission models. IMPORTANCE Antimicrobial resistance is a rising threat to human and animal health. The spread of resistance through the transmission of the symbiotic gut microbiome is of concern and has been explored in theoretical modeling studies. In this study, we employ gregarious insect populations to examine the emergence and transmission of antimicrobial resistance in vivo and validate modeling hypotheses. We find that antimicrobial treatment increases the levels of resistance in treated populations. Most importantly, we show that resistance increased in untreated populations after interacting with the treated ones. The level of resistance transmission was affected by the magnitude and frequency of population mixing. Our results highlight the importance of microbial transmission in the spread of antimicrobial resistance.

The European livestock resistome

“…Recent studies based on human clinical isolates, urban sewage, and experimental and modeling approaches have suggested that the abundance of ARGs is not only a consequence of AMU but also associated with socio-economic factors most likely influencing increased transmission ( 59 – 63 ). Considering whether the effect of the spread of new ARGs (dispersal) is important, or if dispersal effects are minimal compared to large variability in local selection pressures across countries, is an important question in managing future resources for tackling AMR.…”

When does antimicrobial resistance increase bacterial fitness? Effects of dosing, social interactions, and frequency dependence on the benefits of AmpC β-lactamases in broth, biofilms, and a gut infection model

“…We note that previous experiments using injections of Galleria melonella wax moth larvae, a commonly used insect model, also failed to identify fitness costs and lacked the key step of the natural establishment of infection ( Penkova, 2023 ). Infectivity and the production of infectious material are very important for the dynamics of resistance ( Lehtinen et al, 2017 ; Samore et al, 2005 ; zur Wiesch et al, 2011 ), and yet there are few studies quantifying the effects of resistance on transmission even in model hosts ( Bogri et al, 2023 ). Long-term experiments in other animals (cattle) show that a single cephalosporin dose produces only a transient increase in AmpC/ESBL resistance, suggesting fitness costs can return frequencies to low levels ( Levent et al, 2022 ).…”