Bacillus licheniformis escapes from Myxococcus xanthus predation by deactivating myxovirescin A through enzymatic glucosylation

Abstract

Summary Myxococcus xanthus kills susceptible bacteria using myxovirescin A (TA) during predation. However, whether prey cells in nature can escape M. xanthus by developing resistance to TA is unknown. We observed that many field‐isolated Bacillus licheniformis strains could survive encounters with M. xanthus, which was correlated to their TA resistance. A TA glycoside was identified in the broth of predation‐resistant B. licheniformis J32 co‐cultured with M. xanthus, and a glycosyltransferase gene (yjiC) was up‐regulated in J32 after the addition of TA. Hetero‐expressed YjiC‐modified TA to a TA glucoside (TA‐Gluc) by conjugating a glucose moiety to the C‐21 hydroxyl group, and the resulting compound was identical to the TA glycoside present in the co‐culture broth. TA‐Gluc exhibited diminished bactericidal activity due to its weaker binding with LspA, as suggested by in silico docking data. Heterologous expression of the yjiC gene conferred both TA and M. xanthus‐predation resistance to the host Escherichia coli cells. Furthermore, under predatory pressure, B. licheniformis Y071 rapidly developed predation resistance by acquiring TA resistance through the overexpression of yjiC and lspA genes. These results suggest that M. xanthus predation resistance in B. licheniformis is due to the TA deactivation by glucosylation, which is induced in a predator‐mediated manner.

The Predation Strategy of Myxococcus xanthus

“…Streptomyces coelicolor produces an antibiotic, actinorhodin, upon co-cultivation with M. xanthus, which however does not confer a survival advantage (Pérez et al, 2011). Recently, an enzyme released by Bacillus licheniformis was found to glycosylate myxovirescin A, which inactivates the antibiotic and renders the producing strain less susceptible to predation by M. xanthus (Wang et al, 2019).…”

Predatory selection of mucoid, antibiotic resistantPseudomonas putidaphenotype by myxobacteriumCystobacter ferrugineus

“…Building upon previously reported resistance strategies to avoid predatory myxobacteria discovered from predator-prey experiments (11,(17)(18)(19)(20)(21)(22), predation experiments including aeruginosa antibiotic resistance were up-regulated in the survivor phenotype (38,39).…”

“…Compared to features associated with bacterial strategies to avoid protozoan predators, prey avoidance of predatory myxobacteria remains underexplored (Weitere et al, 2005;Justice et al, 2008;Erken et al, 2013;Seiler et al, 2017;Sun et al, 2018). Examples of prey responses correlated with resistance to myxobacterial predation include Escherichia coli biofilm formation (DePas et al, 2014), Bacillus subtilis sporulation and production of bacillaene (Muller et al, 2014;Muller et al, 2015), Bacillus licheniformus glycosylation of the predation-associated metabolite myxovirescin A (Wang et al, 2019), galactoglucan exopolysaccharide production and { PAGE } increased melanin production by Sinorhizobium meliloti (Perez et al, 2014;Contreras-Moreno et al, 2020), and formaldehyde secretion by Pseudomonas aeruginosa (Sutton et al, 2019). All of these features were discovered from predator-prey experiments utilizing the model myxobacterium M. xanthus.…”

The antibiotic crisis: How bacterial predators can help

“…But interspecies cross talk can also trigger the production by prey of specific bioactive compounds for defensive purposes and other resistance mechanisms to counterattack such as biofilm formation [166] , spore differentiation, or induction of new ARGs [167] ( Fig. 3 ).…”