scholarly journals Autotransporter secretion exploits the bacterial actin-homologue

2018 ◽  
Author(s):  
Mahmoud M. Ashawesh ◽  
Robert Markus ◽  
Christopher N. Penfold ◽  
Kim R. Hardie
Keyword(s):  
Bacterial Infection ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Super Resolution ◽  
Resistance Mechanisms ◽  
Dynamic Interaction ◽  
Bacterial Toxins ◽  
Gram Negative ◽  
Bacterial Cytoskeleton ◽  
Development Of Resistance

AbstractBacterial infection of humans, animals and plants relies heavily on secreted proteases that degrade host defences or activate bacterial toxins. The largest family of proteins secreted by Gram-negative pathogenic bacteria, the Autotransporters (ATs), includes key proteolytic virulence factors. There remains uncertainty about the mechanistic steps of the pathway ATs share to exit bacteria, and how it is energetically driven. This study set out to shed light on the AT secretion pathway with the ultimate aim of uncovering novel antimicrobial targets that would be unlikely to trigger the development of resistance mechanisms in bacteria. To do this, two AT virulence factors with distinct proteolytic functions, EspC (secreted from EnteropathogenicEscherichia coli) and AaaA (tethered to the extracellular surface ofPseudomonas aeruginosa) were chosen. EspC and AaaA were fluorescently labelled using two separate methods to establish the localization patterns of ATs as they are secreted from a bacterial cell. Super resolution microscopy revealed that localization of ATs occurs via a helical route along the bacterial cytoskeleton. In addition to requiring the conserved C-terminal β-barrel translocator domain of the AT, we present the first evidence that secretion is dependent on a dynamic interaction with a structure reliant upon the actin homologue MreB and the Sec translocon. These findings provide a step forward in the mechanistic understanding of the secretion of this widely distributed family of proteins that have pivotal roles in bacterial pathogenesis and conserved structural properties that could serve as novel broad-range antimicrobial targets.SignificanceSecreted bacterial proteases facilitate the infection of human, animal and plant hosts by degrading host defences or activating bacterial toxins. The autotransporter family is the largest family of proteins secreted from Gram-negative bacteria, and includes proteolytic virulence factors crucial to bacterial infection. Precisely how autotransporters migrate from the inside to the outside of the cell, and how this movement is energetically driven is a mystery. We demonstrate a spiral pathway of autotransporter secretion, presenting evidence that it involves a dynamic interaction with the actin homologue MreB that comprises the bacterial cytoskeleton. Our findings open the way to unravelling the mechanism of autotransporter secretion and offer the possibility to identify novel antimicrobial targets unlikely to trigger the development of antimicrobial resistance.

scholarly journals Current Update on Intrinsic and Acquired Colistin Resistance Mechanisms in Bacteria

2021 ◽  
Vol 8 ◽  
Author(s):  
Firdoos Ahmad Gogry ◽  
Mohammad Tahir Siddiqui ◽  
Insha Sultan ◽  
Qazi Mohd. Rizwanul Haq
Keyword(s):  
Pathogenic Bacteria ◽  
Lipid A ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Bacterial Surface ◽  
Resistance Determinants ◽  
Neisseria Meningitides

Colistin regained global interest as a consequence of the rising prevalence of multidrug-resistant Gram-negative Enterobacteriaceae. In parallel, colistin-resistant bacteria emerged in response to the unregulated use of this antibiotic. However, some Gram-negative species are intrinsically resistant to colistin activity, such as Neisseria meningitides, Burkholderia species, and Proteus mirabilis. Most identified colistin resistance usually involves modulation of lipid A that decreases or removes early charge-based interaction with colistin through up-regulation of multistep capsular polysaccharide expression. The membrane modifications occur by the addition of cationic phosphoethanolamine (pEtN) or 4-amino-l-arabinose on lipid A that results in decrease in the negative charge on the bacterial surface. Therefore, electrostatic interaction between polycationic colistin and lipopolysaccharide (LPS) is halted. It has been reported that these modifications on the bacterial surface occur due to overexpression of chromosomally mediated two-component system genes (PmrAB and PhoPQ) and mutation in lipid A biosynthesis genes that result in loss of the ability to produce lipid A and consequently LPS chain, thereafter recently identified variants of plasmid-borne genes (mcr-1 to mcr-10). It was hypothesized that mcr genes derived from intrinsically resistant environmental bacteria that carried chromosomal pmrC gene, a part of the pmrCAB operon, code three proteins viz. pEtN response regulator PmrA, sensor kinase protein PmrAB, and phosphotransferase PmrC. These plasmid-borne mcr genes become a serious concern as they assist in the dissemination of colistin resistance to other pathogenic bacteria. This review presents the progress of multiple strategies of colistin resistance mechanisms in bacteria, mainly focusing on surface changes of the outer membrane LPS structure and other resistance genetic determinants. New handier and versatile methods have been discussed for rapid detection of colistin resistance determinants and the latest approaches to revert colistin resistance that include the use of new drugs, drug combinations and inhibitors. Indeed, more investigations are required to identify the exact role of different colistin resistance determinants that will aid in developing new less toxic and potent drugs to treat bacterial infections. Therefore, colistin resistance should be considered a severe medical issue requiring multisectoral research with proper surveillance and suitable monitoring systems to report the dissemination rate of these resistant genes.

scholarly journals Distinction between Antimicrobial Resistance and Putative Virulence Genes Characterization in Plesiomonas shigelloides Isolated from Different Sources

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 85
Author(s):  
Samy Selim ◽  
Mohammed S. Almuhayawi ◽  
Shadi Ahmed Zakai ◽  
Ahmed Attia Salama ◽  
Mona Warrad
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infection ◽  
Virulence Factors ◽  
Virulence Genes ◽  
Aquatic Habitats ◽  
Gram Negative ◽  
Plesiomonas Shigelloides ◽  
Wide Range ◽  
Different Sources ◽  
Human Stool

Plesiomonas shigelloides are gram-negative, thermotolerant, motile, and pleomorphic microorganisms that are only distantly related to those of the Enterobacteriaceae and Vibrionaceae families. One of the most common sources of P. shigelloides contamination is human stool, but it may also be found in a wide range of other animals, plants, and aquatic habitats. Antimicrobial resistance in P. shigelloides from seawater and shellfish was investigated, and pathogenicity involved genes were characterized as part of this study. Out of 384 samples of shellfish, 5.7% included P. shigelloides. The presence of P. shigelloides was also discovered in 5% of the seawater sampled. The antimicrobial resistance of 23 P. shigelloides isolates derived from those samples was investigated. All isolates were sensitive to nalidixic acid, carbenicillin, cephalothin, erythromycin, kanamycin, tetracycline, and ciprofloxacin in the study. Several strains isolated from diseased shellfish were tested for virulence in shellfish by intraperitoneal injections. The LD50 values ranged from 12 × 108 to 3 × 1012 cfu/shellfish. When looking for possible virulence factors that may play a significant role in bacterial infection in the current study, we found that all of these genes were present in these strains. These include genes such as elastase, lipase, flagellin, enterotoxin, and DNases. According to these findings, shellfish may serve as a reservoir for multi-resistant P. shigelloides and help spread virulence genes across the environment.

scholarly journals Fabrication of Zinc Oxide-Xanthan Gum Nanocomposite via Green Route: Attenuation of Quorum Sensing Regulated Virulence Functions and Mitigation of Biofilm in Gram-Negative Bacterial Pathogens

Coatings ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1190
Author(s):  
Fohad Mabood Husain ◽  
Imran Hasan ◽  
Faizan Abul Qais ◽  
Rais Ahmad Khan ◽  
Pravej Alam ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Xanthan Gum ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Cell Surface Hydrophobicity ◽  
Health Concern ◽  
Gram Negative ◽  
Slow Development

The unabated abuse of antibiotics has created a selection pressure that has resulted in the development of antimicrobial resistance (AMR) among pathogenic bacteria. AMR has become a global health concern in recent times and is responsible for a high number of mortalities occurring across the globe. Owing to the slow development of antibiotics, new chemotherapeutic antimicrobials with a novel mode of action is required urgently. Therefore, in the current investigation, we green synthesized a nanocomposite comprising zinc oxide nanoparticles functionalized with extracellular polysaccharide xanthan gum (ZnO@XG). Synthesized nanomaterial was characterized by structurally and morphologically using UV-visible spectroscopy, XRD, FTIR, BET, SEM and TEM. Subinhibitory concentrations of ZnO@XG were used to determine quorum sensing inhibitory activity against Gram-negative pathogens, Chromobacterium violaceum, and Serratia marcescens. ZnO@XG reduced quorum sensing (QS) regulated virulence factors such as violacein (61%), chitinase (70%) in C. violaceum and prodigiosin (71%) and protease (72%) in S. marcescens at 128 µg/mL concentration. Significant (p ≤ 0.05) inhibition of biofilm formation as well as preformed mature biofilms was also recorded along with the impaired production of EPS, swarming motility and cell surface hydrophobicity in both the test pathogens. The findings of this study clearly highlight the potency of ZnO@XG against the QS controlled virulence factors of drug-resistant pathogens that may be developed as effective inhibitors of QS and biofilms to mitigate the threat of multidrug resistance (MDR). ZnO@XG may be used alone or in combination with antimicrobial drugs against MDR bacterial pathogens. Further, it can be utilized in the food industry to counter the menace of contamination and spoilage caused by the formation of biofilms.

Disarming the enemy: targeting bacterial toxins with small molecules

2017 ◽  
Vol 1 (1) ◽  
pp. 31-39
Author(s):  
Alejandro Huerta-Uribe ◽  
Andrew J. Roe
Keyword(s):  
Small Molecules ◽  
Pathogenic Bacteria ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Bacterial Toxin ◽  
Bacterial Strains ◽  
Development Of Resistance ◽  
Enterohaemorrhagic Escherichia Coli ◽  
Life Threatening ◽  
Conventional Antibiotics

The rapid emergence of antibiotic-resistant bacterial strains has prompted efforts to find new and more efficacious treatment strategies. Targeting virulence factors produced by pathogenic bacteria has gained particular attention in the last few years. One of the inherent advantages of this approach is that it provides less selective pressure for the development of resistance mechanisms. In addition, antivirulence drugs could potentially be the answer for diseases in which the use of conventional antibiotics is counterproductive. That is the case for bacterial toxin-mediated diseases, in which the severity of the symptoms is a consequence of the exotoxins produced by the pathogen. Examples of these are haemolytic-uraemic syndrome produced by Shiga toxins, the profuse and dangerous dehydration caused by Cholera toxin or the life-threatening colitis occasioned by clostridial toxins. This review focuses on the recent advances on the development of small molecules with antitoxin activity against Enterohaemorrhagic Escherichia coli, Vibrio cholerae and Clostridium difficile given their epidemiological importance. The present work includes studies of small molecules with antitoxin properties that act directly on the toxin (direct inhibitors) or that act by preventing expression of the toxin (indirect inhibitors).

scholarly journals Candida glabrata: Pathogenicity and Resistance Mechanisms for Adaptation and Survival

2021 ◽  
Vol 7 (8) ◽  
pp. 667
Author(s):  
Yahaya Hassan ◽  
Shu Yih Chew ◽  
Leslie Thian Lung Than
Keyword(s):  
Virulence Factors ◽  
Candida Glabrata ◽  
High Stress ◽  
Hydrolytic Enzymes ◽  
The Elderly ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Diabetic Patients ◽  
Susceptible Host ◽  
Development Of Resistance

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetic patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. This work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to susceptible host surfaces, evading host defences, replicative ageing, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, resistance to neutrophil killings, and development of resistance to antifungal drugs, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

scholarly journals Quorum sensing and Bacterial Pathogenicity: From Molecules to Disease

2011 ◽  
Vol 3 (01) ◽  
pp. 004-011 ◽  
Author(s):  
Antariksh Deep ◽  
Uma Chaudhary ◽  
Varsha Gupta
Keyword(s):  
Quorum Sensing ◽  
Virulence Factors ◽  
Defense Mechanisms ◽  
Pathogenic Bacteria ◽  
Critical Concentration ◽  
Bacterial Species ◽  
Signal Molecules ◽  
Gram Negative ◽  
Host Immune Responses ◽  
Novel Target

ABSTRACT Quorum sensing in prokaryotic biology refers to the ability of a bacterium to sense information from other cells in the population when they reach a critical concentration (i.e. a Quorum) and communicate with them. The "language" used for this intercellular communication is based on small, self-generated signal molecules called as autoinducers. Quorum sensing is thought to afford pathogenic bacteria a mechanism to minimize host immune responses by delaying the production of tissue-damaging virulence factors until sufficient bacteria have amassed and are prepared to overwhelm host defense mechanisms and establish infection. Quorum sensing systems are studied in a large number of gram-negative bacterial species belonging to α, β, and γ subclasses of proteobacteria. Among the pathogenic bacteria, Pseudomonas aeruginosa is perhaps the best understood in terms of the virulence factors regulated and the role the Quorum sensing plays in pathogenicity. Presently, Quorum sensing is considered as a potential novel target for antimicrobial therapy to control multi/all drug-resistant infections. This paper reviews Quorum sensing in gram positive and gram negative bacteria and its role in biofilm formation.

Antibiotics Application Strategies to Control Biofilm Formation in Pathogenic Bacteria

2020 ◽  
Vol 21 (4) ◽  
pp. 270-286 ◽  
Author(s):  
Fazlurrahman Khan ◽  
Dung T.N. Pham ◽  
Sandra F. Oloketuyi ◽  
Young-Mog Kim
Keyword(s):  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Extracellular Polymeric Substances ◽  
Quorum Quenching ◽  
Resistance Mechanisms ◽  
Bacterial Biofilm ◽  
Bacterial Cells ◽  
High Concentration ◽  
Biofilm Inhibition ◽  
Abiotic Surfaces

Background: The establishment of a biofilm by most pathogenic bacteria has been known as one of the resistance mechanisms against antibiotics. A biofilm is a structural component where the bacterial community adheres to the biotic or abiotic surfaces by the help of Extracellular Polymeric Substances (EPS) produced by bacterial cells. The biofilm matrix possesses the ability to resist several adverse environmental factors, including the effect of antibiotics. Therefore, the resistance of bacterial biofilm-forming cells could be increased up to 1000 times than the planktonic cells, hence requiring a significantly high concentration of antibiotics for treatment. Methods: Up to the present, several methodologies employing antibiotics as an anti-biofilm, antivirulence or quorum quenching agent have been developed for biofilm inhibition and eradication of a pre-formed mature biofilm. Results: Among the anti-biofilm strategies being tested, the sub-minimal inhibitory concentration of several antibiotics either alone or in combination has been shown to inhibit biofilm formation and down-regulate the production of virulence factors. The combinatorial strategies include (1) combination of multiple antibiotics, (2) combination of antibiotics with non-antibiotic agents and (3) loading of antibiotics onto a carrier. Conclusion: The present review paper describes the role of several antibiotics as biofilm inhibitors and also the alternative strategies adopted for applications in eradicating and inhibiting the formation of biofilm by pathogenic bacteria.

Antimicrobial properties of actively purified secondary metabolites isolated from different marine organisms

2020 ◽  
Vol 21 ◽  
Author(s):  
Nilushi Indika Bamunu Arachchige ◽  
Fazlurrahman Khan ◽  
Young-Mog Kim
Keyword(s):  
Secondary Metabolites ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Antimicrobial Properties ◽  
Antimicrobial Effect ◽  
Cost Effective ◽  
Resistance Mechanisms ◽  
Marine Organisms ◽  
Antimicrobial Compounds

Background: The treatment of infection caused by pathogenic bacteria becomes one of the serious concerns globally. The failure in the treatment was found due to the exhibition of multiple resistance mechanisms against the antimicrobial agents. Emergence of resistant bacterial species has also been observed due to prolong treatment using conventional antibiotics. To combat these problems, several alternative strategies have been employed using biological and chemically synthesized compounds as antibacterial agents. Marine organisms considered as one of the potential sources for the isolation of bioactive compounds due to the easily available, cost-effective, and eco-friendly. Methods: The online search methodology was adapted for the collection of information related to the antimicrobial properties of marine-derived compounds. These compound has been isolated and purified by different purification techniques, and their structure also characterized. Furthermore, the antibacterial activities have been reported by using broth microdilution as well as disc diffusion assays. Results: The present review paper describes the antimicrobial effect of diverse secondary metabolites which are isolated and purified from the different marine organisms. The structural elucidation of each secondary metabolite has also been done in the present paper, which will help for the in silico designing of the novel and potent antimicrobial compounds. Conclusion: A thorough literature search has been made and summarizes the list of antimicrobial compounds that are isolated from both prokaryotic and eukaryotic marine organisms. The information obtained from the present paper will be helpful for the application of marine compounds as antimicrobial agents against different antibiotic-resistant human pathogenic bacteria.

scholarly journals Healthcare-Associated Laboratory-Confirmed Bloodstream Infections—Species Diversity and Resistance Mechanisms, a Four-Year Retrospective Laboratory-Based Study in the South of Poland

2021 ◽  
Vol 18 (5) ◽  
pp. 2785
Author(s):  
Agnieszka Chmielarczyk ◽  
Monika Pomorska-Wesołowska ◽  
Dorota Romaniszyn ◽  
Jadwiga Wójkowska-Mach
Keyword(s):  
Bloodstream Infections ◽  
Diagnostic Techniques ◽  
Resistance Mechanisms ◽  
Infection Prevention And Control ◽  
The South ◽  
Coagulase Negative Staphylococci ◽  
Aminoglycoside Resistance ◽  
Gram Negative ◽  
Maldi Tof ◽  
Carbapenem Resistant

Introduction: Regardless of the country, advancements in medical care and infection prevention and control of bloodstream infections (BSIs) are an enormous burden of modern medicine. Objectives: The aim of our study was to describe the epidemiology and drug-resistance of laboratory-confirmed BSI (LC-BSIs) among adult patients of 16 hospitals in the south of Poland. Patients and methods: Data on 4218 LC-BSIs were collected between 2016–2019. The identification of the strains was performed using MALDI-TOF. Resistance mechanisms were investigated according to European Committee on Antimicrobial Susceptibility Testing, EUCAST recommendations. Results: Blood cultures were collected from 8899 patients, and LC-BSIs were confirmed in 47.4%. The prevalence of Gram-positive bacteria was 70.9%, Gram-negative 27.8% and yeast 1.4%. The most frequently isolated genus was Staphylococcus (50% of all LC-BSIs), with a domination of coagulase-negative staphylococci, while Escherichia coli (13.7%) was the most frequent Gram-negative bacterium. Over 4 years, 108 (2.6%) bacteria were isolated only once, including species from the human microbiota as well as environmental and zoonotic microorganisms. The highest methicillin resistant Staphylococcus aureus (MRSA) prevalence was in intensive care units (ICUs) (55.6%) but S. aureus with resistance to macrolides, lincosamides and streptogramins B (MLSB) in surgery was 66.7%. The highest prevalence of E. faecalis with a high-level aminoglycoside resistance (HLAR) mechanism was in ICUs, (84.6%), while E. faecium-HLAR in surgery was 83.3%. All cocci were fully glycopeptide-sensitive. Carbapenem-resistant Gram-negative bacilli were detected only in non-fermentative bacilli group, with prevalence 70% and more. Conclusions: The BSI microbiology in Polish hospitals was similar to those reported in other studies, but the prevalence of MRSA and enterococci-HLAR was higher than expected, as was the prevalence of carbapenem-resistant non-fermentative bacilli. Modern diagnostic techniques, such as MALDI-TOF, guarantee reliable diagnosis.

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