scholarly journals Structural Basis for the Lipopolysaccharide Export Activity of the Bacterial Lipopolysaccharide Transport System

2018 ◽  
Vol 19 (9) ◽  
pp. 2680 ◽  
Author(s):  
Greg Hicks ◽  
Zongchao Jia
Keyword(s):  
Protein Complex ◽  
Structural Basis ◽  
Gram Negative Bacteria ◽  
The Novel ◽  
Membrane Stress ◽  
Gram Negative ◽  
Export Activity ◽  
System A ◽  
Continuous Stream ◽  
Dependent Mechanism

Gram-negative bacteria have a dense outer membrane (OM) coating of lipopolysaccharides, which is essential to their survival. This coating is assembled by the LPS (lipopolysaccharide) transport (Lpt) system, a coordinated seven-subunit protein complex that spans the cellular envelope. LPS transport is driven by an ATPase-dependent mechanism dubbed the “PEZ” model, whereby a continuous stream of LPS molecules is pushed from subunit to subunit. This review explores recent structural and functional findings that have elucidated the subunit-scale mechanisms of LPS transport, including the novel ABC-like mechanism of the LptB2FG subcomplex and the lateral insertion of LPS into the OM by LptD/E. New questions are also raised about the functional significance of LptA oligomerization and LptC. The tightly regulated interactions between these connected subcomplexes suggest a pathway that can react dynamically to membrane stress and may prove to be a valuable target for new antibiotic therapies for Gram-negative pathogens.

Structural basis for the recognition of lysozyme by MliC, a periplasmic lysozyme inhibitor in Gram-negative bacteria

2009 ◽  
Vol 378 (2) ◽  
pp. 244-248 ◽  
Author(s):  
Soohwan Yum ◽  
Moon Jong Kim ◽  
Yongbin Xu ◽  
Xiao Ling Jin ◽  
Hee Young Yoo ◽  
...  
Keyword(s):  
Structural Basis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Lysozyme Inhibitor

scholarly journals ComparativeIn VitroActivities of the Novel Antibacterial Finafloxacin against Selected Gram-Positive and Gram-Negative Bacteria Tested in Mueller-Hinton Broth and Synthetic Urine

2011 ◽  
Vol 55 (4) ◽  
pp. 1814-1818 ◽  
Author(s):  
Axel Dalhoff ◽  
Will Stubbings ◽  
Sabine Schubert
Keyword(s):  
Resistance Mechanisms ◽  
Low Ph ◽  
Gram Negative Bacteria ◽  
The Novel ◽  
Gram Negative ◽  
Ph Values ◽  
Synthetic Urine ◽  
Mueller Hinton ◽  
Artificial Urine ◽  
Mueller Hinton Broth

ABSTRACTKill kinetics and MICs of finafloxacin and ciprofloxacin against 34 strains with defined resistance mechanisms grown in cation-adjusted Mueller-Hinton broth (CAMHB) at pH values of 7.2 and 5.8 and in synthetic urine at pH 5.8 were determined. In general, finafloxacin gained activity at low pH values in CAMHB and remained almost unchanged in artificial urine. Ciprofloxacin MICs increased and bactericidal activity decreased strain dependently in acidic CAMHB and particularly in artificial urine.

scholarly journals Structural Basis of a Temporin 1b Analogue Antimicrobial Activity against Gram Negative Bacteria Determined by CD and NMR Techniques in Cellular Environment

2015 ◽  
Vol 10 (4) ◽  
pp. 965-969 ◽  
Author(s):  
Gaetano Malgieri ◽  
Concetta Avitabile ◽  
Maddalena Palmieri ◽  
Luca Domenico D’Andrea ◽  
Carla Isernia ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Structural Basis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Cellular Environment ◽  
Nmr Techniques

scholarly journals Phagocytosis of Gram-negative bacteria by a unique CD14-dependent mechanism

1997 ◽  
Vol 62 (6) ◽  
pp. 786-794 ◽  
Author(s):  
Deborah E. Schiff ◽  
Lois Kline ◽  
Katrin Soldau ◽  
J. D. Lee ◽  
Jerome Pugin ◽  
...  
Keyword(s):  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dependent Mechanism

scholarly journals Revisiting the Gram-Negative Lipoprotein Paradigm

2015 ◽  
Vol 197 (10) ◽  
pp. 1705-1715 ◽  
Author(s):  
Eric D. LoVullo ◽  
Lori F. Wright ◽  
Vincent Isabella ◽  
Jason F. Huntley ◽  
Martin S. Pavelka
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Francisella Tularensis ◽  
Live Vaccine Strain ◽  
Gram Negative Bacteria ◽  
The Novel ◽  
Gram Negative ◽  
Content Type ◽  
Sucrose Medium ◽  
Small Colony ◽  
Increased Susceptibility

ABSTRACTThe processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that thelntgene is not essential to the Gram-negative pathogenFrancisella tularensissubsp.tularensisstrain Schu or to the live vaccine strain LVS. An LVS Δlntmutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δlntmutant. We present a model in which the Lol sorting pathway ofFrancisellahas a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model usingNeisseria gonorrhoeae, which has the same Lol architecture as that ofFrancisella, and found that thelntgene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM.IMPORTANCEThis paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required byFrancisella tularensisorNeisseria gonorrhoeae. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria.

scholarly journals Ab initio Designed Antimicrobial Peptides Against Gram-Negative Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Shravani S. Bobde ◽  
Fahad M. Alsaab ◽  
Guangshuan Wang ◽  
Monique L. Van Hoek
Keyword(s):  
Antibacterial Activity ◽  
Immune System ◽  
Ab Initio ◽  
Gram Negative Bacteria ◽  
The Novel ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Positional Analysis ◽  
Low Salt ◽  
Database Filtering

Antimicrobial peptides (AMPs) are ubiquitous amongst living organisms and are part of the innate immune system with the ability to kill pathogens directly or indirectly by modulating the immune system. AMPs have potential as a novel therapeutic against bacteria due to their quick-acting mechanism of action that prevents bacteria from developing resistance. Additionally, there is a dire need for therapeutics with activity specifically against Gram-negative bacterial infections that are intrinsically difficult to treat, with or without acquired drug resistance. Development of new antibiotics has slowed in recent years and novel therapeutics (like AMPs) with a focus against Gram-negative bacteria are needed. We designed eight novel AMPs, termed PHNX peptides, using ab initio computational design (database filtering technology combined with the novel positional analysis on APD3 dataset of AMPs with activity against Gram-negative bacteria) and assessed their theoretical function using published machine learning algorithms, and finally, validated their activity in our laboratory. These AMPs were tested to establish their minimum inhibitory concentration (MIC) and half-maximal effective concentration (EC50) under CLSI methodology against antibiotic resistant and antibiotic susceptible Escherichia coli and Staphylococcus aureus. Laboratory-based experimental results were compared to computationally predicted activities for each of the peptides to ascertain the accuracy of the computational tools used. PHNX-1 demonstrated antibacterial activity (under high and low-salt conditions) against antibiotic resistant and susceptible strains of Gram-positive and Gram-negative bacteria and PHNX-4 to -8 demonstrated low-salt antibacterial activity only. The AMPs were then evaluated for cytotoxicity using hemolysis against human red blood cells and demonstrated some hemolysis which needs to be further evaluated. In this study, we successfully developed a design methodology to create synthetic AMPs with a narrow spectrum of activity where the PHNX AMPs demonstrated higher antibacterial activity against Gram-negative bacteria compared to Gram-positive bacteria. Thus, these peptides present novel synthetic peptides with a potential for therapeutic use. Based on our findings, we propose upfront selection of the peptide dataset for analysis, an additional step of positional analysis to add to the ab initio database filtering technology (DFT) method, and we present laboratory data on the novel, synthetically designed AMPs to validate the results of the computational approach. We aim to conduct future in vivo studies which could establish these AMPs for clinical use.

scholarly journals Structural basis of cell-surface signaling by a conserved sigma regulator in Gram-negative bacteria

2020 ◽  
Vol 295 (17) ◽  
pp. 5795-5806 ◽  
Author(s):  
Jaime L. Jensen ◽  
Beau D. Jernberg ◽  
Sangita C. Sinha ◽  
Christopher L. Colbert
Keyword(s):  
Cell Surface ◽  
Conformational Changes ◽  
Cd Spectroscopy ◽  
Structural Basis ◽  
Titration Calorimetry ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Regulatory Pathways ◽  
Surface Signaling ◽  
Cell Surface Signaling

Cell-surface signaling (CSS) in Gram-negative bacteria involves highly conserved regulatory pathways that optimize gene expression by transducing extracellular environmental signals to the cytoplasm via inner-membrane sigma regulators. The molecular details of ferric siderophore-mediated activation of the iron import machinery through a sigma regulator are unclear. Here, we present the 1.56 Å resolution structure of the periplasmic complex of the C-terminal CSS domain (CCSSD) of PupR, the sigma regulator in the Pseudomonas capeferrum pseudobactin BN7/8 transport system, and the N-terminal signaling domain (NTSD) of PupB, an outer-membrane TonB-dependent transducer. The structure revealed that the CCSSD consists of two subdomains: a juxta-membrane subdomain, which has a novel all-β-fold, followed by a secretin/TonB, short N-terminal subdomain at the C terminus of the CCSSD, a previously unobserved topological arrangement of this domain. Using affinity pulldown assays, isothermal titration calorimetry, and thermal denaturation CD spectroscopy, we show that both subdomains are required for binding the NTSD with micromolar affinity and that NTSD binding improves CCSSD stability. Our findings prompt us to present a revised model of CSS wherein the CCSSD:NTSD complex forms prior to ferric-siderophore binding. Upon siderophore binding, conformational changes in the CCSSD enable regulated intramembrane proteolysis of the sigma regulator, ultimately resulting in transcriptional regulation.

Structural Basis of Sequential Allosteric Transitions in Tetramericd-Lactate Dehydrogenases from Three Gram-Negative Bacteria

Biochemistry ◽  
2018 ◽  
Vol 57 (37) ◽  
pp. 5388-5406
Author(s):  
Nayuta Furukawa ◽  
Akimasa Miyanaga ◽  
Masahiro Nakajima ◽  
Hayao Taguchi
Keyword(s):  
Structural Basis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Allosteric Transitions ◽  
Lactate Dehydrogenases
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