Aerial Exposure to the Bacterial Volatile Compound Trimethylamine Modifies Antibiotic Resistance of Physically Separated Bacteria by Raising Culture Medium pH

Abstract

Bacteria release a wide diversity of small bioactive molecules that often correspond to secondary metabolites. Among them, volatile molecules produced under various growth conditions were shown to mediate cross-kingdom interactions with plants, nematodes, and fungi. Although the role of volatile compounds in bacterial biology is not well understood, recent reports indicated that they could play a role in airborne interactions between bacteria and influence antibiotic resistance, biofilm formation, and virulence. In this study, we investigated long-distance effects of 14 previously described Escherichia coli volatile compounds upon the bacteria E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis. We show that several of these molecules constitute chemical cues influencing growth, adhesion, and motility in exposed bacteria. Moreover, we show that aerial exposure to trimethylamine (TMA), a volatile compound produced in animal intestines and tissues upon biogenic reduction of trimethylamine oxide (TMAO), modifies the antibiotic resistance profiles of all tested Gram-positive and Gram-negative bacteria. We demonstrate that the TMA mode of action is distinct from that previously described for ammonia and results from nonspecific transient alteration of antibiotic uptake due to pH increase in the environment of bacteria aerially exposed to TMA. Our study therefore presents a new way by which volatile compounds can affect community behavior and structure in physically separated bacteria. It further demonstrates that bacterial gases and volatile compounds mediate chemical interactions, triggering functional responses that play an important role in the development of bacterial communities.

Volatile affairs in microbial interactions

“…For example, exposure of E. coli to volatiles emitted by Burkholderia ambifaria increased its resistance to gentamycin and kanamycin by yet unknown mechanisms (Groenhagen et al, 2013). Exposure to the volatile compound trimethylamine was shown to modify the antibiotic resistance profiles of several Gram-positive and Gram-negative bacteria (Létoffé et al, 2014). In addition, indole, a volatile that has been proposed to act as signalling molecule, can also affect antibiotic resistance.…”

The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants

“…Microbially produced ammonia and amines can mediate long-range intercellular interactions and influence antibiotic resistance [41 -46]. Gaseous ammonia, from bacterial supernatant, and trimethylamine, can decrease resistance to the aminoglycoside antibiotics kanamycin and spectinomycin [45,46].…”

Possible odour-mediated attraction of flies to Bacillus subtilis NRS-762 stationary phase culture

“…Besides the diffusible molecules that partake in signaling processes in liquid and solid medium culture, bacteria also release a variety of volatile compounds [4], where antimicrobial activity is the most direct observable effect. For example, biogenic gaseous ammonia modulates antibiotic resistance in a range of Gram-negative and Gram-positive bacteria [5,6]. Additionally, volatile compounds have also been shown to exert antimicrobial activity towards a broad range of fungi [7][8][9].…”

“…For instance, diffusible small molecules serve as communication agents for coordinating diverse activities between various bacteria in the root rhizosphere. Characterization of the long-range effects of 14 gaseous volatile compounds secreted by Escherichia coli also reveal their myriad effects on biofilm formation, motility pattern and antibiotic resistance in E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis [5].…”