Resident Microbiome Disruption with Antibiotics Enhances Virulence of a Colonizing Pathogen

Abstract

There is growing evidence that symbiotic microbes play key roles in host defense, but less is known about how symbiotic microbes mediate pathogen-induced damage to hosts. Here, we use a natural wildlife disease system, house finches and the conjunctival bacterial pathogen Mycoplasma gallisepticum (MG), to experimentally examine the impact of the ocular microbiome on host damage and pathogen virulence factors during infection. We disrupted the ocular bacterial community of healthy finches using an antibiotic that MG is intrinsically resistant to, then inoculated antibiotic- and sham-treated birds with MG. House finches with antibiotic-disrupted ocular microbiomes had more severe MG-induced conjunctival inflammation than birds with unaltered microbiomes, even after accounting for differences in conjunctival MG load. Furthermore, MG cultures from finches with disrupted microbiomes had increased sialidase enzyme and cytadherence activity, traits associated with enhanced virulence in Mycoplasmas, relative to isolates from sham-treated birds. Variation in sialidase activity and cytadherence among isolates was tightly linked with degree of tissue inflammation in hosts, supporting the consideration of these traits as virulence factors in this system. Overall, our results suggest that microbial dysbiosis can result in enhanced virulence of colonizing pathogens, with critical implications for the health of wildlife, domestic animals, and humans.

Initial description of the core ocular surface microbiome in dogs: Bacterial community diversity and composition in a defined canine population

“…Initial studies in mice suggested that the presence of the ocular microbiome regulates the composition of the tear film, possibly impacting bacterial ability to adhere and infect the conjunctiva . Furthermore, evidence exists to support the beneficial effect of the ocular microbiota in preventing keratitis and other infectious ocular conditions . Characterization of a bacterial community beneficial to ocular surface health may lead to the development of novel therapies to mitigate bacterial disbyosis and conditions associated with it, and should be pursued.…”

Habitat fragmentation is associated with dietary shifts and microbiota variability in common vampire bats

“…dysbiosis of the microbiota may be monitored as an early warning sign about potential downstream effects on host ecology and health(Bahrndorff, Alemu, Alemneh, & Lund Nielsen, 2016;Cheng et al, 2015;Lemieux-Labonté, Simard, Willis, & Lapointe, 2017;Thomason, Mullen, Belden, May, & Hawley, 2017). dysbiosis of the microbiota may be monitored as an early warning sign about potential downstream effects on host ecology and health(Bahrndorff, Alemu, Alemneh, & Lund Nielsen, 2016;Cheng et al, 2015;Lemieux-Labonté, Simard, Willis, & Lapointe, 2017;Thomason, Mullen, Belden, May, & Hawley, 2017).…”

Protective microbiomes can limit the evolution of host pathogen defense

“…) in mice; and against the conjunctival bacterial pathogen Mycoplasma gallisepticum in house finches (Thomason et al. ). Furthermore, the role of individual defensive symbionts on host fitness has been demonstrated both empirically (Vorburger and Perlman ) and theoretically (King and Bonsall ).…”

“…A comparative framing provides one possible approach to testing the resulting predictions. Evidence for protective effects of the microbiome exists across a range of hosts, including against Pseudomonas syringae in horse chestnut trees (Koskella et al 2017b), tomato (Berg and Koskella 2018), and Arabidopsis plants (Innerebner et al 2011); against both salmonella (Kubinak et al 2015) and intestinal infection with Entamoeba histolytica (Watanabe et al 2017) in mice; and against the conjunctival bacterial pathogen Mycoplasma gallisepticum in house finches (Thomason et al 2017). Furthermore, the role of individual defensive symbionts on host fitness has been demonstrated both empirically (Vorburger and Perlman 2018) and theoretically (King and Bonsall 2017).…”