Imbalance of peptidoglycan biosynthesis alters the cell surface charge of .

The bacterial cell wall is composed of a thick layer of peptidoglycan and cell wall polymers, which are either embedded in the membrane or linked to the peptidoglycan backbone and referred to as lipoteichoic acid (LTA) and wall teichoic acid (WTA), respectively. Modifications of the peptidoglycan or WTA backbone can alter the susceptibility of the bacterial cell towards cationic antimicrobials and lysozyme. The human pathogen is intrinsically resistant towards lysozyme, mainly due to deacetylation and -acetylation of the peptidoglycan backbone via PgdA and OatA. Recent studies identified additional factors, which contribute to the lysozyme resistance of this pathogen. One of these is the predicted ABC transporter, EslABC. An mutant is hyper-sensitive towards lysozyme, likely due to the production of thinner and less -acetylated peptidoglycan. Using a suppressor screen, we show here that suppression of phenotypes could be achieved by enhancing peptidoglycan biosynthesis, reducing peptidoglycan hydrolysis or alterations in WTA biosynthesis and modification. The lack of EslB also leads to a higher negative surface charge, which likely stimulates the activity of peptidoglycan hydrolases and lysozyme. Based on our results, we hypothesize that the portion of cell surface exposed WTA is increased in the mutant due to the thinner peptidoglycan layer and that latter one could be caused by an impairment in UDP--acetylglucosamine (UDP-GlcAc) production or distribution.