Berichtigung: Muropeptides in <i>Pseudomonas aeruginosa</i> and their Role as Elicitors of β‐Lactam‐Antibiotic Resistance

Lee, Mijoon; Dhar, Supurna; Benedetti, Stefania De; Hesek, Dušan; Boggess, Bill; Blázquez, Blas; Mathee, Kalai; Mobashery, Shahriar

doi:10.1002/ange.201608482

Cited by 2 publications

(3 citation statements)

References 18 publications

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“…Conversely, when the d , d ‐carboxypeptidase activity of PBP4 is inactivated by the antibiotic the derepressor metabolite is dominant, leading to induction of expression of the ampC gene. Although the fundamental operation of this regulation was long surmised, it is nonetheless gratifying that our crystallographic studies of the effector‐binding domain of P. aeruginosa AmpR complement studies with the same domain of the Citrobacter freundii AmpR, and further match to our analysis of the structural fluctuation within the muropeptide pool in the absence and presence of β‐lactams …”

Section: Abetting the β‐Lactam Antibiotics Against Gram‐negative Bactsupporting

confidence: 65%

Constructing and deconstructing the bacterial cell wall

Fisher

Mobashery

2019

Protein Science

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The history of modern medicine cannot be written apart from the history of the antibiotics. Antibiotics are cytotoxic secondary metabolites that are isolated from Nature. The antibacterial antibiotics disproportionately target bacterial protein structure that is distinct from eukaryotic protein structure, notably within the ribosome and within the pathways for bacterial cell‐wall biosynthesis (for which there is not a eukaryotic counterpart). This review focuses on a pre‐eminent class of antibiotics—the β‐lactams, exemplified by the penicillins and cephalosporins—from the perspective of the evolving mechanisms for bacterial resistance. The mechanism of action of the β‐lactams is bacterial cell‐wall destruction. In the monoderm (single membrane, Gram‐positive staining) pathogen Staphylococcus aureus the dominant resistance mechanism is expression of a β‐lactam‐unreactive transpeptidase enzyme that functions in cell‐wall construction. In the diderm (dual membrane, Gram‐negative staining) pathogen Pseudomonas aeruginosa a dominant resistance mechanism (among several) is expression of a hydrolytic enzyme that destroys the critical β‐lactam ring of the antibiotic. The key sensing mechanism used by P. aeruginosa is monitoring the molecular difference between cell‐wall construction and cell‐wall deconstruction. In both bacteria, the resistance pathways are manifested only when the bacteria detect the presence of β‐lactams. This review summarizes how the β‐lactams are sensed and how the resistance mechanisms are manifested, with the expectation that preventing these processes will be critical to future chemotherapeutic control of multidrug resistant bacteria.

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Section: Abetting the β‐Lactam Antibiotics Against Gram‐negative Bactsupporting

confidence: 65%

Constructing and deconstructing the bacterial cell wall

Fisher

Mobashery

2019

Protein Science

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“…These muropeptides are transported to the cytoplasm by the inner-membrane protein AmpG (Johnson et al , 2013; Fisher & Mobashery, 2014). In the cytoplasm, pentapeptide-containing muropeptides derepress (in P. aeruginosa and many Enterobacteriaceae ) the AmpR transcription regulator so as to initiate β-lactamase expression (among other effects) as a key resistance mechanism (Wiedemann et al , 1998; Balcewich et al , 2010; Balasubramanian et al , 2015; Vadlamani et al , 2015; Lee et al , 2016a; Dik et al , 2017). The enabling function of LTs intimately links muropeptide recycling to antibiotic resistance (Figure 2).…”

Section: The Reaction Products Of Lts Initiate Both Offensive and Defmentioning

confidence: 99%

“…The value of this strategy for further extending the clinical life of β-lactams arises from the appreciation that LTs and PBPs cooperate during cell-wall biosynthesis, in a homeostatic balancing act between construction and demolition of the cell wall (Johnson et al , 2013). The inhibition of PBPs by β-lactams disturbs this equilibrium, and in many pathogenic Gram-negative bacteria the resulting change in the pool of the recycling cell-wall fragments triggers β-lactamase expression (Jacobs et al , 1994; Fisher & Mobashery, 2014; Vadlamani et al , 2015; Lee et al , 2016a; Dik et al , 2017) These observations raise two central questions with respect to LT inhibition. The first is whether an LT inhibitor might suppress the ability of these Gram-negative bacteria to induce β-lactamases.…”

Section: Lts As Targets For Antibiotic Developmentmentioning

confidence: 99%

Lytic transglycosylases: concinnity in concision of the bacterial cell wall

Dik

Marous

Fisher

et al. 2017

Critical Reviews in Biochemistry and Molecular Biology

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The lytic transglycosylases (LTs) are bacterial enzymes that catalyze the non-hydrolytic cleavage of the peptidoglycan structures of the bacterial cell wall. They are not catalysts of glycan synthesis as might be surmised from their name. Notwithstanding the seemingly mundane reaction catalyzed by the LTs, their lytic reactions serve bacteria for a series of astonishingly diverse purposes. These purposes include cell-wall synthesis, remodeling, and degradation; for the detection of cell-wall-acting antibiotics; for the expression of the mechanism of cell-wall-acting antibiotics; for the insertion of secretion systems and flagellar assemblies into the cell wall; as a virulence mechanism during infection by certain Gram-negative bacteria; and in the sporulation and germination of Gram-positive spores. Significant advances in the mechanistic understanding of each of these processes have coincided with the successive discovery of new LTs structures. In this review, we provide a systematic perspective on what is known on the structure-function correlations for the LTs, while simultaneously identifying numerous opportunities for the future study of these enigmatic enzymes.

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Berichtigung: Muropeptides in Pseudomonas aeruginosa and their Role as Elicitors of β‐Lactam‐Antibiotic Resistance

Cited by 2 publications

References 18 publications

Constructing and deconstructing the bacterial cell wall

Constructing and deconstructing the bacterial cell wall

Lytic transglycosylases: concinnity in concision of the bacterial cell wall

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