A New Class of Cell Wall-Recycling l , d -Carboxypeptidase Determines β-Lactam Susceptibility and Morphogenesis in Acinetobacter baumannii

Abstract

To grow efficiently, resist antibiotics, and control the immune response, bacteria recycle parts of their cell wall. A key step in the typical recycling pathway is the reuse of cell wall peptides by an enzyme known as an l , d -carboxypeptidase (LDC). Acinetobacter baumannii , an “urgent-threat” pathogen causing drug-resistant sepsis in hospitals, was previously thought to lack this enzymatic activity due to absence of a known LDC homolog.

The l,d-Transpeptidase LdtAb from Acinetobacter baumannii Is Poorly Inhibited by Carbapenems and Has a Unique Structural Architecture

“…Growth curves for the wild-type parental strain and ΔLdt Ab and ΔLdt Ab +PBP1b­(S/A) mutants were very similar in the logarithmic phase of growth; however, in the stationary phase both mutants grew slightly slower (in the order: ΔLdt Ab +PBP1b­(S/A) slower than ΔLdt Ab ) and had lower CFU/mL than the parental strain (Figure ). In a recent publication, it was also shown that the ΔLdt Ab mutant of A. baumannii ATCC 17978 had a similar growth rate as the parental strain . In contrast, growth of the ΔLdt Ab +ΔPBP2 mutant of A. baumannii CIP 70.10 was affected more dramatically.…”

“…In a recent publication, it was also shown that the ΔLdt Ab mutant of A. baumannii ATCC 17978 had a similar growth rate as the parental strain. 37 In contrast, growth of the ΔLdt Ab +ΔPBP2 mutant of A. baumannii CIP 70.10 was affected more dramatically. We observed a significant (∼5fold) decrease in the number of viable cells during the first two hours of incubation.…”

“…Very recently, it was established that ElsL (also known as LdtK) is not an LDT but rather a cytoplasmic L,D-carboxypeptidase, a member of a previously unidentified class of cell wall recycling enzymes. 37 This study demonstrated that the A. baumannii genome encodes only a single LDT, which the authors renamed from LdtJ to Ldt Ab .…”

“…Analysis of the cell wall muropeptide composition of this A. baumannii triple mutant demonstrated that decrease in the amount of d,d -cross-linked muropeptide is compensated by a significant increase of the l,d -cross-linked species. Very recently, it was established that ElsL (also known as LdtK) is not an LDT but rather a cytoplasmic l,d -carboxypeptidase, a member of a previously unidentified class of cell wall recycling enzymes . This study demonstrated that the A. baumannii genome encodes only a single LDT, which the authors renamed from LdtJ to Ldt Ab .…”

Peptidoglycan Recycling Promotes Outer Membrane Integrity and Carbapenem Tolerance in Acinetobacter baumannii

“…While this study was in progress, two other groups reported a characterization of ElsL as a cytoplasmic ld -carboxypeptidase ( 67 , 68 ). Our results here support this conclusion.…”