Summary
A bioRxiv preprint reports that the bacterial enzyme LysM can kill several Gram-negative hospital pathogens and disrupt their biofilms, particularly when combined with EDTA. Tests included laboratory experiments and a human airway organoid model, not treatment in patients.
A bioRxiv preprint reports that LysM, an enzyme encoded in bacterial genomes, can kill several Gram-negative hospital pathogens and disrupt their biofilms. The researchers found its strongest activity against Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacter cloacae, especially when LysM was combined with EDTA. The work includes laboratory tests and a human airway organoid infection model, rather than patient treatment.
How LysM attacks bacteria
LysM is a glycoside hydrolase: an enzyme that breaks bonds in sugar-containing molecules. The researchers used structural modelling and targeted mutations to identify it as a peptidoglycan-specific hydrolase. Peptidoglycan is the mesh-like material that helps give bacterial cells their shape and structural strength.
For many Gram-negative bacteria, an outer membrane shields the peptidoglycan from substances outside the cell. EDTA can weaken this barrier by binding metal ions that help stabilise it. In the preprint’s experiments, adding EDTA allowed externally supplied LysM to trigger rapid cell lysis and kill bacteria.
The team reports that the LysM–EDTA combination acted against multiple Gram-negative pathogens in the ESKAPE group, with the greatest activity against P. aeruginosa, A. baumannii and E. cloacae. The authors note that these three pathogens also carry LysM homologues in their genomes. LysM supplied without EDTA also inhibited the growth of several pathogens, according to the abstract.
Biofilm results and combinations
Biofilms are communities of bacteria attached to a surface and embedded in a protective matrix. The researchers report that LysM, EDTA and PslG—a glycosidase that degrades part of the biofilm matrix—had potent activity against P. aeruginosa biofilms. This included drug-resistant clinical isolates in laboratory experiments and a human airway organoid biofilm-infection model.
In single-cell tracking experiments, LysM prevented P. aeruginosa biofilm formation, alongside reduced attachment to surfaces and longer bacterial doubling times. The preprint also reports that LysM increased the activity of antibiotics from several major classes, including colistin, tobramycin, ciprofloxacin and tetracycline.
The findings point to a possible strategy that combines damage to the bacterial cell wall with disruption of the outer membrane or biofilm matrix. The authors also suggest that LysM-like enzymes found in other bacterial and phage genomes could be investigated for antimicrobial use.
Evidence stage
The report is a preprint and has not been peer reviewed. Its evidence, as described in the abstract, comes from mechanistic laboratory work, bacterial growth and biofilm experiments, and an organoid model. The authors report little toxicity to human cells, but these findings do not amount to evidence of safety or effectiveness in patients. LysM is a research candidate, not an established treatment.