Structure of a short-chain dehydrogenase/reductase (SDR) within a genomic island from a clinical strain of<i>Acinetobacter baumannii</i>

Shah, Bhumika S.; Tetu, Sasha G.; Harrop, S.J.; Paulsen, Ian T.; Mabbutt, Bridget C.

doi:10.1107/s2053230x14019785

Cited by 6 publications

(4 citation statements)

References 33 publications

(34 reference statements)

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“…Because SDR proteins show such a diverse range of functions whilst maintaining structural features, it can be difficult to assign biological function from sequence or structural information alone. Structures for classical and extended SDRs from A. baumannii have been reported previously 16 , 55 , 56 .…”

Section: Introductionmentioning

confidence: 84%

Insights into Acinetobacter baumannii fatty acid synthesis 3-oxoacyl-ACP reductases

Cross

Adams

Waters

et al. 2021

Sci Rep

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Treatments for ‘superbug’ infections are the focus for innovative research, as drug resistance threatens human health and medical practices globally. In particular, Acinetobacter baumannii (Ab) infections are repeatedly reported as difficult to treat due to increasing antibiotic resistance. Therefore, there is increasing need to identify novel targets in the development of different antimicrobials. Of particular interest is fatty acid synthesis, vital for the formation of phospholipids, lipopolysaccharides/lipooligosaccharides, and lipoproteins of Gram-negative envelopes. The bacterial type II fatty acid synthesis (FASII) pathway is an attractive target for the development of inhibitors and is particularly favourable due to the differences from mammalian type I fatty acid synthesis. Discrete enzymes in this pathway include two reductase enzymes: 3-oxoacyl-acyl carrier protein (ACP) reductase (FabG) and enoyl-ACP reductase (FabI). Here, we investigate annotated FabG homologs, finding a low-molecular weight 3-oxoacyl-ACP reductase, as the most likely FASII FabG candidate, and high-molecular weight 3-oxoacyl-ACP reductase (HMwFabG), showing differences in structure and coenzyme preference. To date, this is the second bacterial high-molecular weight FabG structurally characterized, following FabG4 from Mycobacterium. We show that ΔAbHMwfabG is impaired for growth in nutrient rich media and pellicle formation. We also modelled a third 3-oxoacyl-ACP reductase, which we annotated as AbSDR. Despite containing residues for catalysis and the ACP coordinating motif, biochemical analyses showed limited activity against an acetoacetyl-CoA substrate in vitro. Inhibitors designed to target FabG proteins and thus prevent fatty acid synthesis may provide a platform for use against multidrug-resistant pathogens including A. baumannii.

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Section: Introductionmentioning

confidence: 84%

Insights into Acinetobacter baumannii fatty acid synthesis 3-oxoacyl-ACP reductases

Cross

Adams

Waters

et al. 2021

Sci Rep

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“…Here we selected an A . baumannii SDR enzyme with no known structure, and for which the closest sequence identity to any known protein structure in the Protein Data Bank is ~37% to expand the repertoire of previously determined SDR proteins from this important bacterium [ 25 , 35 , 36 ]. The protein structure was determined by X-ray crystallography and compared with related SDRs to provide a platform for further studies.…”

Section: Resultsmentioning

confidence: 99%

Crystallographic structure determination and analysis of a potential short-chain dehydrogenase/reductase (SDR) from multi-drug resistant Acinetobacter baumannii

Ghafoori,

Abdollahpour,

Shirmast

et al. 2023

PLoS ONE

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Bacterial antibiotic resistance remains an ever-increasing worldwide problem, requiring new approaches and enzyme targets. Acinetobacter baumannii is recognised as one of the most significant antibiotic-resistant bacteria, capable of carrying up to 45 different resistance genes, and new drug discovery targets for this organism is an urgent priority. Short-chain dehydrogenase/reductase enzymes are a large protein family with >60,000 members involved in numerous biosynthesis pathways. Here, we determined the structure of an SDR protein from A. baumannii and assessed the putative co-factor comparisons with previously co-crystalised enzymes and cofactors. This study provides a basis for future studies to examine these potential co-factors in vitro.

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“…Upregulated in U was a short-chain dehydrogenase family protein (3.9-fold vs. MiG). Its structure has been described from a genomic island of a clinical strain of A. baumannii [ 88 ]. Additionally, abundant in U was the pyruvate dehydrogenase E1 component (3.1-fold > NGM).…”

Section: Resultsmentioning

confidence: 99%

Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer

et al. 2022

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(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance.

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Structure of a short-chain dehydrogenase/reductase (SDR) within a genomic island from a clinical strain ofAcinetobacter baumannii

Cited by 6 publications

References 33 publications

Insights into Acinetobacter baumannii fatty acid synthesis 3-oxoacyl-ACP reductases

Insights into Acinetobacter baumannii fatty acid synthesis 3-oxoacyl-ACP reductases

Crystallographic structure determination and analysis of a potential short-chain dehydrogenase/reductase (SDR) from multi-drug resistant Acinetobacter baumannii

Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer

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