Peptidoglycan editing provides immunity to Acinetobacter baumannii during bacterial warfare

Abstract

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacterium Acinetobacter baumannii strain ATCC 17978 produces, secretes, and incorporates the noncanonical d-amino acid d-lysine into its PG during stationary phase. We show that PG editing increases the competitiveness of A. baumannii during bacterial warfare by providing immunity against peptidoglycan-targeting T6SS effectors from various bacterial competitors. In contrast, we found that d-Lys production is detrimental to pathogenesis due, at least in part, to the activity of the human enzyme d-amino acid oxidase (DAO), which degrades d-Lys producing H2O2 toxic to bacteria. Phylogenetic analyses indicate that the last common ancestor of A. baumannii had the ability to produce d-Lys. However, this trait was independently lost multiple times, likely reflecting the evolution of A. baumannii as a human pathogen.

Activity, delivery, and diversity of Type VI secretion effectors

“…Effectors can also be encoded without adjacent immunity genes when they are active against targets not found in the effector‐producing bacterium, for instance, targets only found in eukaryotes (Zhang et al, 2012). Importantly, some bacteria can be intrinsically resistant to the anti‐bacterial toxins due to the absence or difference of the target or due to specific responses (Hersch et al, 2020; Kamal et al, 2020; Le et al, 2020). Most immunity proteins are small single‐domain proteins that typically engage in highly specific interactions with their cognate toxins and occlude their active sites (Ding et al, 2012; Dong et al, 2013a; Robb et al, 2016; Wang et al, 2013; Whitney et al, 2013; Zhang et al, 2012; Zhang et al, 2013a; Zhang et al, 2013b), or lock them in a dysfunctional conformation (Lu et al, 2014).…”

Role of Recipient Susceptibility Factors During Contact-Dependent Interbacterial Competition

“…Besides RS factors, recent studies have revealed the presence of immunity-independent resistance in recipient cell that were nicely reviewed by Robitaille et al (2020). These recipient defense factors or mechanisms include physical barriers such as exopolysaccharide (Toska et al, 2018), envelope stress responses (Hersch et al, 2020), or peptidoglycan editing (Le et al, 2020). Growing evidence of the involvement of recipient factors in either enhancing T6SS toxicity or defense against T6SS indicates an evolutionary arms race during interbacterial competition, which may play roles in shaping microbiome.…”

Multidrug Resistant Acinetobacter Isolates Release Resistance Determinants Through Contact-Dependent Killing and Bacteriophage Lysis

“…When using the A. baumannii 17978 strain and its isogenic hcp mutant, we observed minimal killing of A. johnsonii, while A. radioresistens and A. lwoffii were extensively killed and the T6SS could only account for part of this reduction. This killing could be due to an undescribed CDI system that does not resemble known CDI systems in that strain or other combat mechanisms expressed by the 17978 strain (Le et al, 2020). These recent findings are particularly relevant to consider in environments that are under constant selective pressure, such as the poultry gut (Singer and Hofacre, 2006).…”