Resistance to host antimicrobial peptides mediates resilience of gut commensals during infection and aging inDrosophila

Abstract

Resilience to short-term perturbations, like inflammation, is a fundamental feature of microbiota, yet the underlying mechanisms of microbiota resilience are incompletely understood. Here we show that Lactiplantibacillus plantarum, a major Drosophila commensal, stably colonizes the fruit fly gut during infection and is resistant to Drosophila antimicrobial peptides (AMPs). By transposon screening, we identified L. plantarum mutants sensitive to AMPs. These mutants were impaired in peptidoglycan O-acetylation or teichoic acid D-alanylation, resulting in increased negative cell surface charge and higher affinity to cationic AMPs. AMP-sensitive mutants were cleared from the gut after infection and aging-induced gut inflammation in wild-type, but not in AMP-deficient flies, suggesting that resistance to host AMPs is essential for commensal resilience in an inflamed gut environment. Thus, our work reveals that in addition to the host immune tolerance to the microbiota, commensal-encoded resilience mechanisms are necessary to maintain the stable association between host and microbiota during inflammation.

When the microbiome shapes the host: immune evolution implications for infectious disease

“…For instance, Mycobacterium abscessus is combatted by certain types of phagocytes, with the caveat that phagocytosis of M. abscessus may even protect the bacteria from the host AMP response [27,28]. Indeed, many Gram-positive bacteria seemingly ignore host AMPs [23,29], which could also depend on their thick cell wall made of peptidoglycan and techoic acids [30]. As such, mechanisms of defence like ROS bursts or phagocytosis may be specifically useful against Gram-positive bacteria because alternatives like AMPs are ineffective for one reason or another.…”

“…This work has been particularly surprising for a number of reasons. First, when the seven classic fly AMP gene families are deleted, there is almost no effect seen upon infections by many Gram-positive bacteria (including S. aureus, Staphylococcus pneumoniae, Enterococcus faecalis, Listeria monocytogenes, Bacillus subtilis, M. abscessus and Lactiplantibacillus plantarum) [23,27,29,30].…”