Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila

Abstract

Antimicrobial peptides are host-encoded antibiotics that combat invading microbes and help shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is evolutionarily adapted to its microbiome. Here we characterize the function and evolution of the Diptericin antimicrobial peptide family of Diptera. Using mutations affecting the two Diptericins (Dpt) of D. melanogaster, we reveal the specific role of DptA against the pathogen Providencia rettgeri and DptB against the gut mutualist Acetobacter. Strikingly, presence of DptA- or DptB-like genes across Diptera correlates with the presence of Providencia and Acetobacter in their environment. Moreover, presence of DptA- and DpB-like genes is sufficient to predict host resistance against infection by these bacteria across a broad range of fly species. Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family, and reveals how the host immune repertoire adapts itself to changing microbial environments.

Antimicrobial peptides do not directly contribute to aging inDrosophila, but improve lifespan by preventing dysbiosis

“…However, our results do support a role for AMPs in regulating the microbiome over aging. Indeed, we recently showed that Acetobacter microbiome bacteria grow out of control in the microbiome of ∆AMP14 flies (Marra et al, 2021), and later confirmed that Diptericin B has a highly specific and important role in suppressing Acetobacter growth after systemic infection, which causes bloating similar to what we saw in nora virus-infected flies (Hanson et al, 2022b). This phenotype of Acetobacter systemic infection could help explain why flies bloat upon infection by enteric pathogens (like nora virus or Drosophila C virus), or upon aging, given the eventual invasion of gut microbes into the hemolymph (Clark et al, 2015;Rera et al, 2012).…”

“…1C). These stocks also often showed abdominal bloating at older ages pre-empting mortality (personal observation), similar to bloating seen in flies infected with Drosophila C virus (Chtarbanova et al, 2014), or after systemic infection with some strains of Acetobacter bacteria (Hanson et al, 2022b). We thus suspect nora virus contamination contributed greatly to the early mortality of our iso w 1118 flies in our first lifespan experiments (Fig.…”

“…The specific microbiome of a given research group could also change the impact of germ-free conditions. For instance, different Acetobacter strains have different virulence to the fly during systemic infection (Hanson et al, 2022b), which accompanies aging and intestinal barrier dysfunction (Clark et al, 2015;Rera et al, 2012). Indeed, use of ΔAMP14 flies revealed a key role of AMPs to control Acetobacter levels in the microbiome, and accordingly, ΔAMP14 flies have increased Acetobacter loads upon aging (Marra et al, 2021).…”

“…Drosophila AMPs also contribute downstream of the Toll pathway to combat fungi and to a lesser extent Gram-positive bacterial infection, although Bomanins play a more prominent role against these micro-organisms (Carboni et al, 2021; Clemmons et al, 2015; Hanson et al, 2019a). Use of fly lines carrying combinations of AMP mutations revealed that they can function either additively or synergistically against some microbes, but in some cases AMPs exhibit striking specificity, with one peptide contributing most of the AMP-dependent defence against a specific pathogen (Hanson et al, 2019a; Hanson et al, 2022a; Hanson et al, 2022b; Unckless et al, 2016). Drosophila AMPs are also important to control the fly microbiome downstream of the Imd pathway, particularly for their role in regulating Gram-negative bacteria like Acetobacter (Marra et al, 2021).…”

Antimicrobial peptides do not directly contribute to aging in Drosophila, but improve lifespan by preventing dysbiosis

“…Drosophila AMPs also contribute downstream of the Toll pathway to combat fungal and, to a lesser extent, Gram-positive bacterial infection, although Bomanins play a more prominent role against these micro-organisms ( Carboni et al, 2021 ; Clemmons et al, 2015 ; Hanson et al, 2019a ). Use of fly lines carrying combinations of AMP mutations revealed that they can function either additively or synergistically against some microbes, but, in some cases, AMPs exhibit striking specificity, with one peptide contributing most of the AMP-dependent defence against a specific pathogen ( Hanson et al, 2019a , 2022a , b ; Unckless et al, 2016 ). Drosophila AMPs are also important to control the fly microbiome downstream of the Imd pathway, particularly for their role in regulating Gram-negative bacteria like Acetobacter ( Marra et al, 2021 ).…”