The research found that removing a bacterial enzyme (ltgA) in Neisseria gonorrhoeae makes the bacteria produce more cell‑wall building blocks and become more vulnerable to common antibiotics and the human antimicrobial peptide LL‑37. This shows LL‑37 can kill the bacteria more easily when its cell‑wall synthesis is disrupted.

Lytic transglycosylase A in Neisseria gonorrhoeae cleaves the β-1,4-glycosidic bond between peptidoglycan (PG) monomers to liberate 1,6-anhydro-PG fragments that are either recycled or released as cytotoxic fragments. To gain further insight into the effect of LtgA on cellular processes in Neisseria gonorrhoeae, we performed a proteomic analysis comparing wild-type and an isogenic ltgA null mutant strain. Proteins were separated by two-dimensional gel electrophoresis and identified by MALDI-TOF mass spectrometry, which revealed several proteins that were increased in their level of expression upon loss of LtgA. The most notable changes corresponded to enzymes related to aminosugar and pyrimidine metabolism. Quantitative real-time RT-PCR of mRNA from a ltgA null strain confirmed increased transcription of genes encoding enzymes involved in UDP-N-acetylglucosamine (UDP-GlcNAc) synthesis, a major precursor in PG and lipooligosaccharide (LOS) synthesis, during normal growth conditions and following exposure to penicillin. We also found that the ltgA mutant strains were more susceptible to β-lactam antibiotics, vancomycin, and the human-cathelicidin antibacterial peptide, LL-37, than their corresponding wild-type parental strains. Our results suggest that increased expression of enzymes responsible for production UDP-GlcNAc is an adaptive response due to inactivation of ltgA and/or exposure to penicillin.