scholarly journals Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin

2015 ◽  
Vol 112 (7) ◽  
pp. 2210-2215 ◽  
Author(s):  
Harry A. Dailey ◽  
Svetlana Gerdes ◽  
Tamara A. Dailey ◽  
Joseph S. Burch ◽  
John D. Phillips
Keyword(s):  
Antimicrobial Resistance ◽  
Ferrous Iron ◽  
Chlorophyll Synthesis ◽  
Significant Shift ◽  
Biosynthesis Pathway ◽  
Metabolic Intermediates ◽  
Gram Positive Bacteria ◽  
Tetrapyrrole Synthesis ◽  
Prokaryotic Genomes ◽  
Pharmacological Target

It has been generally accepted that biosynthesis of protoheme (heme) uses a common set of core metabolic intermediates that includes protoporphyrin. Herein, we show that the Actinobacteria and Firmicutes (high-GC and low-GC Gram-positive bacteria) are unable to synthesize protoporphyrin. Instead, they oxidize coproporphyrinogen to coproporphyrin, insert ferrous iron to make Fe-coproporphyrin (coproheme), and then decarboxylate coproheme to generate protoheme. This pathway is specified by three genes namedhemY,hemH, andhemQ. The analysis of 982 representative prokaryotic genomes is consistent with this pathway being the most ancient heme synthesis pathway in the Eubacteria. Our results identifying a previously unknown branch of tetrapyrrole synthesis support a significant shift from current models for the evolution of bacterial heme and chlorophyll synthesis. Because some organisms that possess this coproporphyrin-dependent branch are major causes of human disease, HemQ is a novel pharmacological target of significant therapeutic relevance, particularly given high rates of antimicrobial resistance among these pathogens.

Measurement of ferrochelatase activity using a novel assay suggests that plastids are the major site of haem biosynthesis in both photosynthetic and non-photosynthetic cells of pea (Pisum sativum L.)

2002 ◽  
Vol 362 (2) ◽  
pp. 423-432 ◽  
Author(s):  
Johanna E. CORNAH ◽  
Jennifer M. ROPER ◽  
Davinder Pal SINGH ◽  
Alison G. SMITH
Keyword(s):  
Ferrous Iron ◽  
Specific Activity ◽  
Higher Plants ◽  
Protoporphyrin Ix ◽  
Chlorophyll Synthesis ◽  
Marker Enzyme ◽  
Hexane Extraction ◽  
Higher Plant ◽  
Major Site ◽  
Haem Biosynthesis

Ferrochelatase is the terminal enzyme of haem biosynthesis, catalysing the insertion of ferrous iron into the macrocycle of protoporphyrin IX, the last common intermediate of haem and chlorophyll synthesis. Its activity has been reported in both plastids and mitochondria of higher plants, but the relative amounts of the enzyme in the two organelles are unknown. Ferrochelatase is difficult to assay since ferrous iron requires strict anaerobic conditions to prevent oxidation, and in photosynthetic tissues chlorophyll interferes with the quantification of the product. Accordingly, we developed a sensitive fluorimetric assay for ferrochelatase that employs Co2+ and deuteroporphyrin in place of the natural substrates, and measures the decrease in deuteroporphyrin fluorescence. A hexane-extraction step to remove chlorophyll is included for green tissue. The assay is linear over a range of chloroplast protein concentrations, with an average specific activity of 0.68nmol·min−1·mg of protein−1, the highest yet reported. The corresponding value for mitochondria is 0.19nmol·min−1·mg of protein−1. The enzyme is inhibited by N-methylprotoporphyrin, with an estimated IC50 value of ≈ 1nM. Using this assay we have quantified ferrochelatase activity in plastids and mitochondria from green pea leaves, etiolated pea leaves and pea roots to determine the relative amounts in the two organelles. We found that, in all three tissues, greater than 90% of the activity was associated with plastids, but ferrochelatase was reproducibly detected in mitochondria, at levels greater than the contaminating plastid marker enzyme, and was latent. Our results indicate that plastids are the major site of haem biosynthesis in higher plant cells, but that mitochondria also have the capacity for haem production.

scholarly journals Biosynthesis of the Unique Wall Teichoic Acid of Staphylococcus aureus Lineage ST395

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Volker Winstel ◽  
Patricia Sanchez-Carballo ◽  
Otto Holst ◽  
Guoqing Xia ◽  
Andreas Peschel
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Biosynthesis Pathway ◽  
Glycerol Phosphate ◽  
Coagulase Negative Staphylococci ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Wall Teichoic Acids

ABSTRACT The major clonal lineages of the human pathogen Staphylococcus aureus produce cell wall-anchored anionic poly-ribitol-phosphate (RboP) wall teichoic acids (WTA) substituted with d-Alanine and N-acetyl-d-glucosamine. The phylogenetically isolated S. aureus ST395 lineage has recently been found to produce a unique poly-glycerol-phosphate (GroP) WTA glycosylated with N-acetyl-d-galactosamine (GalNAc). ST395 clones bear putative WTA biosynthesis genes on a novel genetic element probably acquired from coagulase-negative staphylococci (CoNS). We elucidated the ST395 WTA biosynthesis pathway and identified three novel WTA biosynthetic genes, including those encoding an α-O-GalNAc transferase TagN, a nucleotide sugar epimerase TagV probably required for generation of the activated sugar donor substrate for TagN, and an unusually short GroP WTA polymerase TagF. By using a panel of mutants derived from ST395, the GalNAc residues carried by GroP WTA were found to be required for infection by the ST395-specific bacteriophage Φ187 and to play a crucial role in horizontal gene transfer of S. aureus pathogenicity islands (SaPIs). Notably, ectopic expression of ST395 WTA biosynthesis genes rendered normal S. aureus susceptible to Φ187 and enabled Φ187-mediated SaPI transfer from ST395 to regular S. aureus. We provide evidence that exchange of WTA genes and their combination in variable, mosaic-like gene clusters have shaped the evolution of staphylococci and their capacities to undergo horizontal gene transfer events. IMPORTANCE The structural highly diverse wall teichoic acids (WTA) are cell wall-anchored glycopolymers produced by most Gram-positive bacteria. While most of the dominant Staphylococcus aureus lineages produce poly-ribitol-phosphate WTA, the recently described ST395 lineage produces a distinct poly-glycerol-phosphate WTA type resembling the WTA backbone of coagulase-negative staphylococci (CoNS). Here, we analyzed the ST395 WTA biosynthesis pathway and found new types of WTA biosynthesis genes along with an evolutionary link between ST395 and CoNS, from which the ST395 WTA genes probably originate. The elucidation of ST395 WTA biosynthesis will help to understand how Gram-positive bacteria produce highly variable WTA types and elucidate functional consequences of WTA variation.

scholarly journals Re-thinking antimicrobial resistance transmission dynamics: a meta-analysis of cross-sectional studies at referral hospitals in Uganda

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 878
Author(s):  
Gerald Mboowa ◽  
Ivan Sserwadda ◽  
Dickson Aruhomukama
Keyword(s):  
Antimicrobial Resistance ◽  
Transmission Dynamics ◽  
Gram Positive ◽  
Cross Sectional ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Extended Spectrum ◽  
Hospital Environments ◽  
Referral Hospitals ◽  
Cross Sectional Studies

Background: Antimicrobial resistance threatens the achievements of modern medicine as well as the sustainability of effective global public health responses to the threat posed by infectious diseases. Extended-spectrum β-lactamase production in bacteria provides the main mechanism of resistance in gram-negative bacteria, particularly those belonging to the Enterobacteriaceae family as well as gram-positive bacteria. This study hence aimed at providing insights into the potential role of in-patients, their immediate hospital environments, out-patients, and their communities in the transmission of antimicrobial resistance via identifying gram-negative and gram-positive bacteria commonly isolated in samples collected from each of these patients/sites as well as their antimicrobial susceptibility profiles using extended-spectrum β-lactamase production in the same as the basis. Methods: Our study reviewed four cross-sectional studies conducted at national and regional referral hospitals in Uganda. Data on bacterial aetiology and antimicrobial susceptibility testing retrieved from the studies was imported into Microsoft Excel, cleaned, sand then exported to IBM SPSS statistics (version 16) for statistical analysis. The databases used were PubMed and Embase.  Results: We report that; Escherichia coli and Klebsiella pneumoniae are the most prevalent Enterobacteriaceae species in the samples that were collected in the studies reviewed; these species account for the highest proportions of extended-spectrum β-lactamase producers; Staphylococcus aureus is the most prevalent of the gram-positive bacteria isolated from the same samples, and accounts for the highest proportions of extended-spectrum β-lactamase producers in the gram-positive bacteria isolated, and similar Enterobacteriaceae species and gram-positive bacteria, are predominant in samples from in-patients, their immediate hospital environments, and out-patients. Conclusion: The insights provided indicate antimicrobial resistance transmission dynamics be re-thought and more comprehensive studies aimed at investigating the same be done to ascertain the source and transmission routes of antimicrobial-resistant bacteria in clinical settings.

scholarly journals Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

An alpha/beta chimeric peptide molecular brush for eradicating MRSA biofilms and persister cells to mitigate antimicrobial resistance

2020 ◽  
Vol 8 (24) ◽  
pp. 6883-6889 ◽  
Author(s):  
Ximian Xiao ◽  
Si Zhang ◽  
Sheng Chen ◽  
Yuxin Qian ◽  
Jiayang Xie ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Resistant ◽  
Excellent Performance ◽  
Persister Cells ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Chimeric Peptide ◽  
Alpha Beta ◽  
Chimeric Polypeptide

An α/β chimeric polypeptide molecular brush shows excellent performance in eradicating established biofilms, persister cells, and clinically isolated multi-drug resistant Gram-positive bacteria.

Multifunctional BODIPY for effective inactivation of Gram-positive bacteria and promotion of wound healing

2021 ◽  
Author(s):  
Chaonan Li ◽  
Yite Li ◽  
Qihang Wu ◽  
Tingting Sun ◽  
Zhigang Xie
Keyword(s):  
Wound Healing ◽  
Photodynamic Therapy ◽  
Antimicrobial Resistance ◽  
Infectious Diseases ◽  
Human Health ◽  
Bacterial Infections ◽  
Alternative Therapies ◽  
Gram Positive ◽  
Gram Positive Bacteria

Bacterial infectious diseases and antimicrobial resistance seriously endanger human health, so alternative therapies for bacterial infections are urgently needed. Recently, photodynamic therapy against bacteria has shown great potential because of...

scholarly journals Antimicrobial resistance rates in gram-positive bacteria do not drive glycopeptides use

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181358 ◽  
Author(s):  
Beryl Primrose Gladstone ◽  
Andrea Cona ◽  
Parichehr Shamsrizi ◽  
Tuba Vilken ◽  
Winfred V. Kern ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Resistance Rates
Sign in / Sign up

Export Citation Format

Share Document