The apolipoprotein N-acyl transferase Lnt is dispensable for growth in Acinetobacter species

Gwin, Celena M.; Prakash, Natalia; Belisario, J Christian; Haider, Lubaina; Rosen, Marlene L.; Martinez, Luis R.; Rigel, Nathan W.

doi:10.1099/mic.0.000726

Cited by 21 publications

(21 citation statements)

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“…For some time, lgt , lspA , lnt and lol have been considered to be essential genes in all Gram-negative bacteria and thus have attracted attention as potential new targets for antibiotherapy [13–15]. However, a recent study showed that lnt is dispensable in Francisella tularensis , Neisseria gonorrhoeae , Acinetobacter baylyi and Acinetobacter baumannii and that its absence does not preclude targeting to the outer membrane [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Role of the unique, non-essential phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt) in Corynebacterium glutamicum

et al. 2020

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Bacterial lipoproteins are secreted proteins that are post-translationally lipidated. Following synthesis, preprolipoproteins are transported through the cytoplasmic membrane via the Sec or Tat translocon. As they exit the transport machinery, they are recognized by a phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt), which converts them to prolipoproteins by adding a diacylglyceryl group to the sulfhydryl side chain of the invariant Cys+1 residue. Lipoprotein signal peptidase (LspA or signal peptidase II) subsequently cleaves the signal peptide, liberating the α-amino group of Cys+1, which can eventually be further modified. Here, we identified the lgt and lspA genes from Corynebacterium glutamicum and found that they are unique but not essential. We found that Lgt is necessary for the acylation and membrane anchoring of two model lipoproteins expressed in this species: MusE, a C. glutamicum maltose-binding lipoprotein, and LppX, a Mycobacterium tuberculosis lipoprotein. However, Lgt is not required for these proteins’ signal peptide cleavage, or for LppX glycosylation. Taken together, these data show that in C. glutamicum the association of some lipoproteins with membranes through the covalent attachment of a lipid moiety is not essential for further post-translational modification.

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Section: Introductionmentioning

confidence: 99%

Role of the unique, non-essential phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt) in Corynebacterium glutamicum

et al. 2020

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“…This high homology of the fusion protein and subsequent pathway probing identified this protein as LolF, a distinct protein among certain gram-negative bacteria namely Neisseria, Francisella, and Acinetobacter (42,47). LolF was shown to accept di-acylated lipoproteins as compared to the rejection of di-acylated lipoproteins by LolCDE (41).…”

Section: Synthesis Of Lipoproteins Begins In the Cytoplasmmentioning

confidence: 95%

“…If destined for the OM the periplasmic chaperone LolA then shuttles the lipoproteins to the OM receptor LolB for inclusion into the OM (38,(44)(45)(46). In Francisella spp., a fusion protein resembling E. coli LolC/LolE exists that shares high homology among functional domains of the transport system (41). This high homology of the fusion protein and subsequent pathway probing identified this protein as LolF, a distinct protein among certain gram-negative bacteria namely Neisseria, Francisella, and Acinetobacter (42,47).…”

Section: Synthesis Of Lipoproteins Begins In the Cytoplasmmentioning

confidence: 99%

“…Classically it was thought that Lnt-mediated tri-acylation was an essential requirement for recognition by the Lol system and subsequent lipoprotein trafficking. However, Lnt was found to be nonessential in some Gram-negative bacteria including Francisella, Neisseria, and Acinetobacter (40,41). The loss of Lnt is not without detriment, as the absence of a third acylation interrupts lipoprotein trafficking resulting in visible growth defects such as increased OM permeability in Acinetobacter spp.…”

Section: Synthesis Of Lipoproteins Begins In the Cytoplasmmentioning

confidence: 99%

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Biogenesis of Lipoproteins in Gram-Negative Bacteria: 50 Years of Progress

et al. 2021

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The outer membrane is the defining characteristic of Gram-negative bacteria and is crucial for the maintenance of cellular integrity. Lipoproteins are an essential component of this outer membrane and regulate broad cellular functions ranging from efflux, cellular physiology, antibiotic resistance, and pathogenicity. In the canonical model of lipoprotein biogenesis, lipoprotein precursors are first synthesized in the cytoplasm prior to extensive modifications by the consecutive action of three key enzymes: diacylglyceryl transferase (Lgt), lipoprotein signal peptidase A (LspA), and apolipoprotein N-acyltransferase (Lnt). This enzymatic process modifies lipoprotein precursors for subsequent trafficking by the Lol pathway. The function of these three enzymes were originally thought to be essential, however, in some Gram-negative bacteria, namely Acinetobacter baylyi, the third enzyme Lnt is dispensable. Here we review the function and significance of Lgt, LspA, and Lnt in outer membrane biogenesis and how non-canonical models of lipoprotein processing in Acinetobacter spp. can enhance our understanding of lipoprotein modifications and trafficking.

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“…The essential nature of Lnt is not completely conserved in proteobacteria. Recent studies demonstrate that Francisella tularensis , Neisseria gonorrhoeae (LoVullo et al, 2015), Neisseria meningitidis (da Silva et al, 2017), Acinetobacter spp (Gwin et al, 2018), and Helicobacter pylori (McClain et al, 2020) are viable under laboratory conditions in the absence of Lnt. This phenomenon is possibly related to noncanonical Lol machinery in which LolF functions as LolCE in the translocation of OM lipoproteins, however, the basis and extent of this is not fully understood (see below).…”

Section: Becoming Maturementioning

confidence: 99%

Mode of action of lipoprotein modification enzymes—Novel antibacterial targets

Legood

Boneca

Buddelmeijer

2020

Molecular Microbiology

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Volkmar Braun first discovered bacterial lipoproteins in 1973 through the identification of a fatty-acid modification of Lpp, or Braun's lipoprotein, in E. coli (Hantke and Braun, 1973). Through early biochemical and genetics studies and more recent structural analysis, the lipoprotein modification pathway is increasingly well understood. A general consensus exists regarding the well-studied tripartite stages of the lipoprotein modification pathway. Upon insertion into the cytoplasmic membrane, a diacylglyceryl group is added to the lipoprotein, the membrane-spanning signal peptide is cleaved and the protein stays membrane anchored by its diacylglyceryl moiety. Finally, N-acylation results in the formation of mature triacylated lipoprotein (Figure 1). In diderm bacteria, including proteobacteria and some high GC content Gram-positive bacteria, including Streptomyces, Corynebacteria, and Mycobacteria, lipoproteins are triacylated following this classical pathway, although in some instances Lnt and/or Lsp are not essential components for cell viability (discussed below). In monoderm bacteria it was long thought that only diacylated lipoproteins existed; however, recent studies illustrate that alternative lipid modifications occur in firmicutes and mollicutes, but not all enzymes catalyzing these reactions have been

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The apolipoprotein N-acyl transferase Lnt is dispensable for growth in Acinetobacter species

Cited by 21 publications

References 50 publications

Role of the unique, non-essential phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt) in Corynebacterium glutamicum

Role of the unique, non-essential phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt) in Corynebacterium glutamicum

Biogenesis of Lipoproteins in Gram-Negative Bacteria: 50 Years of Progress

Mode of action of lipoprotein modification enzymes—Novel antibacterial targets

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