Lactobacillus spp. attenuate antibiotic-induced immune and microbiota dysregulation in honey bees

Brendan A Daisley,Gregor Reid,Kait F Al,Andrew P Pitek,Kyrillos M Faragalla,Graham J Thompson,John A Chmiel,Jeremy P Burton,Anna M Chernyshova,Shaeley Gibbons

doi:10.1038/s42003-020-01259-8

Brendan A Daisley, Gregor Reid + Show 8 more

Open Access

https://doi.org/10.1038/s42003-020-01259-8

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Abstract

Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera). Here, we show that routine antibiotic administration with oxytetracycline selectively increased tetB (efflux pump resistance gene) abundance in the gut microbiota of adult workers while concurrently depleting several key symbionts known to regulate immune function and nutrient metabolism such as Frischella perrera and Lactobacillus Firm-5 strains. These microbial changes were functionally characterized by decreased capped brood counts (marker of hive nutritional status and productivity) and reduced antimicrobial capacity of adult hemolymph (indicator of immune competence). Importantly, combination therapy with three immunostimulatory Lactobacillus strains could mitigate antibiotic-associated microbiota dysbiosis and immune deficits in adult workers, as well as maximize the intended benefit of oxytetracycline by suppressing larval pathogen loads to near-undetectable levels. We conclude that microbial-based therapeutics may offer a simple but effective solution to reduce honey bee disease burden, environmental xenobiotic exposure, and spread of antimicrobial resistance.

Highlights

Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera)
Testing this in honey bees, it was found that larval samples from LX3-treated hives exhibited significantly lower levels of P. larvae at week 2 and week 4 compared to both no treatment control (NTC; P < 0.0001 for both) and vehicle-treated (P = 0.0011 and P = 0.0014) hives, respectively
Similar results were observed in adults with samples from LX3-supplemented hives demonstrating a significantly lower P. larvae load compared to both the NTC group (P = 0.0002 and P = 0.0003) and vehicletreated group (P < 0.0001 for both) at 2 and 4 weeks, respectively

Summary

Introduction

Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera). We show that routine antibiotic administration with oxytetracycline selectively increased tetB (efflux pump resistance gene) abundance in the gut microbiota of adult workers while concurrently depleting several key symbionts known to regulate immune function and nutrient metabolism such as Frischella perrera and Lactobacillus Firm-5 strains These microbial changes were functionally characterized by decreased capped brood counts (marker of hive nutritional status and productivity) and reduced antimicrobial capacity of adult hemolymph (indicator of immune competence). Despite susceptibility or resistance, OTC is unable to treat P. larvae spores in the comb, which can act as a source of reinfection To address these issues and guard against the potentially rapid evolution of resistance, it is prudent to test alternative control measures, which so far include hygienic breeding[12], use of bioactive essential oils[13], bacteriophage therapy[14], synthetic indoles with anti-germination properties[15], and supplementation of hives with lactic acid bacteria[16,17,18]. We evaluated how treatment augmentation with LX3 following OTC exposure influences antibiotic recovery rates as evaluated by immune functionality, microbial homeostasis, and hive productivity

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