scholarly journals Type V Protein Secretion Pathway: the Autotransporter Story

2004 ◽  
Vol 68 (4) ◽  
pp. 692-744 ◽  
Author(s):  
Ian R. Henderson ◽  
Fernando Navarro-Garcia ◽  
Mickaël Desvaux ◽  
Rachel C. Fernandez ◽  
Dlawer Ala'Aldeen
Keyword(s):  
Protein Secretion ◽  
Bacterial Infections ◽  
Protein Translocation ◽  
Research Field ◽  
Secreted Proteins ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
V Protein ◽  
Secretion Pathway ◽  
Type V

SUMMARY Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function.

scholarly journals Flagellar Localization of a Helicobacter pylori Autotransporter Protein

mBio ◽  
2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Jana N. Radin ◽  
Jennifer A. Gaddy ◽  
Christian González-Rivera ◽  
John T. Loh ◽  
Holly M. Scott Algood ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Infections ◽  
Secreted Proteins ◽  
Wild Type ◽  
Gram Negative ◽  
Content Type ◽  
Ulcer Disease ◽  
H Pylori ◽  
Type V

ABSTRACTHelicobacter pyloricontains four genes that are predicted to encode proteins secreted by the autotransporter (type V) pathway. One of these, the pore-forming toxin VacA, has been studied in great detail, but thus far there has been very little investigation of three VacA-like proteins. We show here that all three VacA-like proteins are >250 kDa in mass and localized on the surface ofH. pylori. The expression of the threevacA-like genes is upregulated duringH. pyloricolonization of the mouse stomach compared toH. pylorigrowthin vitro, and a wild-typeH. pyloristrain outcompeted each of the three corresponding isogenic mutant strains in its ability to colonize the mouse stomach. One of the VacA-like proteins localizes to a sheath that overlies the flagellar filament and bulb, and therefore, we designate it FaaA (flagella-associated autotransporter A). In comparison to a wild-typeH. pyloristrain, an isogenicfaaAmutant strain exhibits decreased motility, decreased flagellar stability, and an increased proportion of flagella in a nonpolar site. The flagellar localization of FaaA differs markedly from the localization of other known autotransporters, and the current results reveal an important role of FaaA in flagellar localization and motility.IMPORTANCEThe pathogenesis of most bacterial infections is dependent on the actions of secreted proteins, and proteins secreted by the autotransporter pathway constitute the largest family of secreted proteins in pathogenic Gram-negative bacteria. In this study, we analyzed three autotransporter proteins (VacA-like proteins) produced byHelicobacter pylori, a Gram-negative bacterium that colonizes the human stomach and contributes to the pathogenesis of gastric cancer and peptic ulcer disease. We demonstrate that these three proteins each enhance the capacity ofH. pylorito colonize the stomach. Unexpectedly, one of these proteins (FaaA) is localized to a sheath that overliesH. pyloriflagella. The absence of FaaA results in decreasedH. pylorimotility as well as a reduction in flagellar stability and a change in flagellar localization. The atypical localization of FaaA reflects a specialized function of this autotransporter designed to optimizeH. pyloricolonization of the gastric niche.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals The antimicrobial potential of cannabidiol

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Angela M. Kavanagh ◽  
Alysha G. Elliott ◽  
Bing Zhang ◽  
Soumya Ramu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Modern Medicine ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
New Class ◽  
Clostridioides Difficile ◽  
Excellent Activity ◽  
Induce Resistance ◽  
First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

scholarly journals Protein Secretion by Gram-negative Bacteria

1989 ◽  
Vol 264 (29) ◽  
pp. 17462-17468
Author(s):  
C d'Enfert ◽  
I Reyss ◽  
C Wandersman ◽  
A P Pugsley
Keyword(s):  
Protein Secretion ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals An overview of carbapenem, its resistance and therapeutic options for infections caused by carbapenem resistant bacteria

2020 ◽  
Vol 9 (9) ◽  
pp. 1454
Author(s):  
Hari P. Nepal ◽  
Rama Paudel
Keyword(s):  
Bacterial Infections ◽  
Carbapenem Resistance ◽  
Therapeutic Options ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
Carbapenem Resistant ◽  
The World

Carbapenems are beta-lactam drugs that have broadest spectrum of activity. They are commonly used as the drugs of last resort to treat complicated bacterial infections. They bind to penicillin binding proteins (PBPs) and inhibit cell wall synthesis in bacteria. Important members that are in clinical use include doripenem, ertapenem, imipenem, and meropenem. Unlike other members, imipenem is hydrolyzed significantly by renal dehydropeptidase; therefore, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin. Carbapenems are usually administered intravenously due to their low oral bioavailability. Most common side effects of these drugs include nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Increasing resistance to these antibiotics is being reported throughout the world and is posing a threat to public health.  Primary mechanisms of carbapenem resistance include expulsion of drug and inactivation of the drug by production of carbapenemases which may not only hydrolyze carbapenem, but also cephalosporin, penicillin, and aztreonam. Resistance especially among Gram negative bacteria is of much concern since there are only limited therapeutic options available for infections caused by carbapenem resistant Gram-negative bacterial pathogens. Commonly used drugs to treat such infections include polymyxins, fosfomycin and tigecycline.

scholarly journals Bacteria causing ventriculoperitoneal shunt infections in a Kenyan population

2015 ◽  
Vol 15 (2) ◽  
pp. 150-155 ◽  
Author(s):  
Naomi Ochieng' ◽  
Humphrey Okechi ◽  
Susan Ferson ◽  
A. Leland Albright
Keyword(s):  
Ventriculoperitoneal Shunt ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Infectious Complications ◽  
Gram Negative Bacteria ◽  
Shunt Insertion ◽  
Gram Negative ◽  
Western Literature ◽  
Sub Saharan ◽  
Few Data

OBJECT Ventriculoperitoneal shunt (VPS) infections are a major cause of morbidity and mortality in patients with hydrocephalus. Most data about these infections come from the Western literature. Few data about infecting organisms in Africa are available, yet knowledge of these organisms is important for the prevention and treatment of infectious complications. The purpose of this study was to determine the organisms cultured from infected shunts in a rural Kenyan hospital. METHODS The authors conducted a retrospective study of patients with VPS infections recorded in the neurosurgical database of BethanyKids at Kijabe Hospital between September 2010 and July 2012. RESULTS Among 53 VPS infections confirmed by culture, 68% occurred in patients who were younger than 6 months. Seventy-nine percent of the infections occurred within 2 months after shunt insertion. Only 51% of infections were caused by Staphylococcus species (Staphylococcus aureus 25%, other Staphylococcus species 26%), whereas 40% were caused by gram-negative bacteria. All S. aureus infections and 79% of other Staphylococcus infections were sensitive to cefazolin, but only 1 of 21 gram-negative bacteria was sensitive to it. The majority of gram-negative bacterial infections were multidrug resistant, but 17 of the 20 gram-negative bacteria were sensitive to meropenem. Gram-negative bacterial infections were associated with worse outcomes. CONCLUSIONS The high proportion of gram-negative infections differs from data in the Western literature, in which Staphylococcus epidermidis is by far the most common organism. Once a patient is diagnosed with a VPS infection in Kenya, immediate treatment is recommended to cover both gram-positive and gram-negative bacterial infections. Data from other Sub-Saharan countries are needed to determine if those countries have the same increased frequency of gram-negative infections.

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