An overview of protein moonlighting in bacterial infection

2014 ◽  
Vol 42 (6) ◽  
pp. 1720-1727 ◽  
Author(s):  
Brian Henderson
Keyword(s):  
Virulence Factors ◽  
Bacterial Infections ◽  
Active Sites ◽  
Pathogenic Bacteria ◽  
Glyoxylate Cycle ◽  
Bacterial Species ◽  
Tca Cycle ◽  
Bacterial Protein ◽  
Protein Families ◽  
Moonlighting Proteins

We are rapidly returning to a world in which bacterial infections are a major health issue. Pathogenic bacteria are able to colonize and cause pathology due to the possession of virulence factors such as adhesins, invasins, evasins and toxins. These are generally specifically evolved proteins with selective actions. It is, therefore, surprising that most human bacterial pathogens employ moonlighting proteins as virulence factors. Currently, >90 bacterial species employ one or more moonlighting protein families to aid colonization and induce disease. These organisms employ 90 moonlighting bacterial protein families and these include enzymes of the glycolytic pathway, tricarboxylic acid (TCA) cycle, hexosemonophosphate shunt, glyoxylate cycle and a range of other metabolic enzymes, proteases, transporters and, also, molecular chaperones and protein-folding catalysts. These proteins have homologues in eukaryotes and only a proportion of the moonlighting proteins employed are solely bacterial in origin. Bacterial moonlighting proteins can be divided into those with single moonlighting functions and those with multiple additional biological actions. These proteins contribute significantly to the population of virulence factors employed by bacteria and some are obvious therapeutic targets. Where examined, bacterial moonlighting proteins bind to target ligands with high affinity. A major puzzle is the evolutionary mechanism(s) responsible for bacterial protein moonlighting and a growing number of highly homologous bacterial moonlighting proteins exhibit widely different moonlighting actions, suggesting a lack in our understanding of the mechanism of evolution of protein active sites.

scholarly journals Potentiation of Tobramycin by Silver Nanoparticles against Pseudomonas aeruginosa Biofilms

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Marc B. Habash ◽  
Mara C. Goodyear ◽  
Amber J. Park ◽  
Matthew D. Surette ◽  
Emily C. Vis ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Silver Nanoparticles ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Acute Infection ◽  
Public Health Problem ◽  
Chronic Infections ◽  
Content Type

ABSTRACT Increasing antibiotic resistance among pathogenic bacterial species is a serious public health problem and has prompted research examining the antibacterial effects of alternative compounds and novel treatment strategies. Compounding this problem is the ability of many pathogenic bacteria to form biofilms during chronic infections. Importantly, these communities are often recalcitrant to antibiotic treatments that show effectiveness against acute infection. The antimicrobial properties of silver have been known for decades, but recently silver and silver-containing compounds have seen renewed interest as antimicrobial agents for treating bacterial infections. The goal of this study was to assess the ability of citrate-capped silver nanoparticles (AgNPs) of various sizes, alone and in combination with the aminoglycoside antibiotic tobramycin, to inhibit established Pseudomonas aeruginosa biofilms. Our results demonstrate that smaller 10-nm and 20-nm AgNPs were more effective at synergistically potentiating the activity of tobramycin. Visualization of biofilms treated with combinations of 10-nm AgNPs and tobramycin reveals that the synergistic bactericidal effect may be caused by disrupting cellular membranes. Minimum biofilm eradication concentration (MBEC) assays using clinical P. aeruginosa isolates shows that small AgNPs are more effective than larger AgNPs at inhibiting biofilms, but that the synergy effect is likely a strain-dependent phenomenon. These data suggest that small AgNPs synergistically potentiate the activity of tobramycin against P. aeruginosa in vitro and may reveal a potential role for AgNP/antibiotic combinations in treating patients with chronic infections in a strain-specific manner.

scholarly journals Computational evidence of a new allosteric communication pathway between active sites and putative regulatory sites in the alanine racemase ofMycobacterium tuberculosis

2018 ◽  
Author(s):  
Jayanthy Jyothikumar ◽  
Sushil Chandani ◽  
Tangirala Ramakrishna
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Discovery ◽  
Side Effects ◽  
Active Site ◽  
Bacterial Infections ◽  
Active Sites ◽  
Pyridoxal Phosphate ◽  
Bacterial Species ◽  
Alanine Racemase ◽  
Docking Simulations

AbstractAlanine racemase, a popular drug target fromMycobacterium tuberculosis, catalyzes the biosynthesis of D-alanine, an essential component in bacterial cell walls. With the help of elastic network models of alanine racemase fromMycobacterium tuberculosis, we show that the mycobacterial enzyme fluctuates between two undiscovered states—a closed and an open state. A previous experimental screen identified several drug-like lead compounds against the mycobacterial alanine racemase, whose inhibitory mechanisms are not known. Docking simulations of the inhibitor leads onto the mycobacterial enzyme conformations obtained from the dynamics of the enzyme provide first clues to a putative regulatory role for two new pockets targeted by the leads. Further, our results implicate the movements of a short helix, behind the communication between the new pockets and the active site, indicating allosteric mechanisms for the inhibition. Based on our findings, we theorize that catalysis is feasible only in the open state. The putative regulatory pockets and the enzyme fluctuations are conserved across several alanine racemase homologs from diverse bacterial species, mostly pathogenic, pointing to a common regulatory mechanism important in drug discovery.Author summaryIn spite of the discovery of many inhibitors against the TB-causing pathogenMycobacterium tuberculosis, only a very few have reached the market as effective TB drugs. Most of the marketed TB drugs induce toxic side effects in patients, as they non-specifically target human cells in addition to pathogens. One such TB drug, D-cycloserine, targets pyridoxal phosphate moiety non-specifically regardless of whether it is present in the pathogen or the human host enzymes. D-cycloserine was developed to inactivate alanine racemase in TB causing pathogen. Alanine racemase is a bacterial enzyme essential in cell wall synthesis. Serious side effects caused by TB drugs like D-cycloserine, lead to patients’ non-compliance with treatment regimen, often causing fatal outcomes. Current drug discovery efforts focus on finding specific, non-toxic TB drugs. Through computational studies, we have identified new pockets on the mycobacterial alanine racemase and show that they can bind drug-like compounds. The location of these pockets away from the pyridoxal phosphate-containing active site, make them attractive target sites for novel, specific TB drugs. We demonstrate the presence of these pockets in alanine racemases from several pathogens and expect our findings to accelerate the discovery of non-toxic drugs against TB and other bacterial infections.

scholarly journals Evaluating the risk of bacterial infections associated with the most handled Iraqi notes in Kalar

2019 ◽  
Vol 4 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Hassan Mohammad Tawfeeq ◽  
Mohammed Hassan Fatah ◽  
Ahmed Mohammed Tofiq
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Coagulase Negative Staphylococcus ◽  
Fresh Sample ◽  
Mannitol Salt Agar ◽  
E Coli ◽  
Paper Currency ◽  
Currency Note ◽  
And Staphylococcus Aureus

Every day new sources of microbial and especially bacterial infections are reported, which are not taken into account, the fact that these sources have been implicated in the outbreaks of these infections. The goals of the current research focused on the exploration of the scope of microbial pollution of the widely traded paper currency notes of the Iraqi currencies (250, 1000 and 5000 Iraqi Dinars) in Kalar city. 300 banknotes (100 samples for each of the denominations under investigation) in circulation were gathered from different categories of Kalar population and one fresh sample for each of the three currencies (control negative). Each bill was rinsed in 5 ml D.W then cultured on Nutrient agar, Mannitol Salt agar and MacConkey agar, respectively, then incubated at 37 ºC for up to 48 hours. Results revealed the rate of microbial contamination, specifically bacterial ones as 94%, 68%, and 60%, respectively on the denominations of 250, 1000, and 5000 of Iraqi Dinars. In a descending order, and with regard to the prevalence rate, bacterial species contaminated 250, 1000 and 5000 Iraqi denominations respectively were as follows: 55.31%, 32.35% and 36.66% for Bacillus sp.; 14.89%, 38.23% and 20% for coagulase-negative Staphylococcus; 8.51%, 8.82% and 20% for E. coli; 2.12%, 11.76 and 20% for Pseudomonas sp.; 2.12% for each of Klebsiella sp., and Salmonella sp.; 10.63% and 4.25% for Enterobacter sp. and Staphylococcus aureus, respectively, and only on 250 denomination;  2.94% and 5.88% for each of Corynebacterium sp. and Serratia sp. only on 1000 currency note; lastly, 3.33% for Proteus sp. on 5000 IQD only. These outcomes suggest that bacterial contamination of Iraqi Dinars, specifically the 250 denomination is risky and could be regarded as the real source of infectious diseases with the most dangerous pathogenic bacteria.  

In-vitro evaluation of cisplatin nanoparticles encompass natural polymer

2020 ◽  
Vol 3 (1) ◽  
pp. 1-6
Author(s):  
Bhavani J ◽  
Sunil Kumar Prajapati ◽  
Ravichandran S
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Research Work ◽  
Dilution Method ◽  
Bacterial Strains ◽  
Active Components ◽  
Synthetic Drugs

Opportunistic bacterial infections are common in the various parts of human body. In recent years bacterial species have shown resistance against a number of synthetic drugs. This study measured the antibacterial activity of bacterial strains against five common pathogenic bacteria related strains. Cup plate method and two fold serial dilution method were used to evaluated by antibacterial activity by the help of different bacterial related strains. The results revealed that Cisplatin (CIP) using natural as a polymer showed a minimum inhibitory concentration (MIC) at 250 mg/ml to 500 mg/ml of the broth against all bacterial strains. CIP using natural as a polymer was prepared different doses1000 μg/ml and 2000 μg/ ml and measured zone of inhibition dose dementedly reduced when compared to standard. The CIP using natural as a polymer exhibited strong anti-bacterial activity against five different species of bacteria and this may be attributed to various active components. Our research work has been indicated Nanoparticles containing CIP using natural as a polymer formulated for the enhanced anti-cancer activity through antimicrobial mechanism. 

Phage-mediated dissemination of virulence factors in pathogenic bacteria facilitated by antibiotic growth promoters in animals: a perspective

2017 ◽  
Vol 18 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Migma Dorji Tamang ◽  
Hoon Sunwoo ◽  
Byeonghwa Jeon
Keyword(s):  
Antibiotic Resistance ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Growth Promotion ◽  
Bacterial Species ◽  
Agricultural Practice ◽  
Growth Promoters ◽  
Antibiotic Resistant ◽  
The World ◽  
Antibiotic Growth Promoters

AbstractAddition of sub-therapeutic antibiotics to the feed of food-producing animals for growth promotion and disease prevention has become a common agricultural practice in many countries. The emergence of antibiotic-resistant pathogens is a looming concern associated with the use of antibiotic growth promoters (AGPs) around the world. In addition, some studies have shown that AGPs may not only affect antibiotic resistance but may also stimulate the dissemination of virulence factors via bacteriophages. Although only a few studies are currently available in the literature regarding this topic, in this article we endeavor to provide a perspective about how AGPs would impact the transmission of virulence factors by horizontal gene transfer via phages in a few pathogenic bacterial species significant to livestock production.

scholarly journals Diversity And Antibiograms of Secondary Bacterial Isolates From Cutaneous Leishmaniasis Wounds

2021 ◽  
Author(s):  
Comfort Yeboaa ◽  
Vivian Etsiapa Boamah ◽  
Hayford Odoi ◽  
Rhoda Owusu-Ntim ◽  
Yaw Duah Boakye ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Healing Process ◽  
Diffusion Method ◽  
Beta Lactam ◽  
Providencia Rettgeri ◽  
Beta Lactam Antibiotics ◽  
Agar Disc

Abstract Background: Leishmaniasis is a vector borne disease caused by an intracellular protozoan parasite. The presence of secondary bacterial infections in cutaneous leishmaniasis wounds exacerbate lesion development and could lead to delay in the healing process. Little is also known about the different bacteria species co-infecting leishmaniasis wounds and their sensitivity patterns in Ghana. This study sought to determine the resistance patterns of bacteria co-infecting cutaneous leishmaniasis wounds from selected communities in the Nkwanta district.Methods: Various bacteria were isolated and characterized from exudates obtained from wound swabs collected with sterile cotton tipped applicators. Confirmation of bacterial identity was done using the analytical profile index and the matrix-assisted laser desorption/ionization time of flight mass spectrometry. Antibiotic susceptibility tests were performed using agar disc diffusion method according to the Clinical and Laboratory Standards Institute breakpoint values.Results: A total of 42 secondary bacteria were isolated from the wounds among which S. aureus was the most predominant (31%). Other pathogenic bacteria that colonized the wounds included Bacillus subtilis (23.8%), Pantoea spp(11.9%), Klebsiella pneumoniea (7.1%), Enterobacter cloacae (7.1%), Aeromonas spp (4.8%), Serratia marcescens (4.8%),Serratia liquefacien (2.4%), Serratia plymutheca (2.4%), Providencia rettgeri (2.4%) and Cronobacter spp (2.4%). Majority of the isolates were obtained from Agoufie (21.4%), Baasare (19%), and Gekrong (16.7%). Most of the isolates were resistant to beta-lactam antibiotics and the third generation cephalosporin. Notably, 84.6% of the S. aureus isolates were methicillin and ciprofloxacin resistant whilst 92.3% were resistant to ampicllin. About sixty-nine percent (69.2%) showed intermediate susceptibility to Erythromycin. Additionally, S. plymutheca was resistant to all the test antibiotics. All the K. pneumoniae and E. cloacae isolates showed resistance to ampicillin, cefotaxime, ceftriaxone, ciprofloxacin, amikacin, aztreonam and meropenem but only 66.7% of these isolates were resistant to piperacillin. All isolates of Providencia rettgeri, Cronobacter spp, S. marcescen, S. liquefacien were resistant to all the beta-lactam antibiotics.Conclusion: This study suggests colonization of cutaneous leishmaniasis wounds with varied bacterial species that are mostly resistant to beta-lactam group of antibiotics.

scholarly journals CLIQ-BID: A method to quantify bacteria-induced damage to eukaryotic cells by automated live-imaging of bright nuclei

2017 ◽  
Author(s):  
Yann Wallez ◽  
Stéphanie Bouillot ◽  
Emmanuelle Soleilhac ◽  
Philippe Huber ◽  
Ina Attrée ◽  
...  
Keyword(s):  
High Throughput ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Ex Vivo ◽  
Morphological Changes ◽  
Cell Damage ◽  
Bacterial Species ◽  
Eukaryotic Cell ◽  
Live Imaging ◽  
Quantitative Detection

ABSTRACTPathogenic bacteria induce eukaryotic cell damage which range from discrete modifications of signalling pathways, to morphological alterations and even to cell death. Accurate quantitative detection of these events is necessary for studying host-pathogen interactions and for developing strategies to protect host organisms from bacterial infections. Investigation of morphological changes is cumbersome and not adapted to high-throughput and kinetics measurements. Here, we describe a simple and cost-effective method based on automated analysis of live cells with stained nuclei, which allows real-time quantification of bacteria-induced eukaryotic cell damage at single-cell resolution. We demonstrate that this automated high-throughput microscopy approach permits screening of libraries composed of interference-RNA, bacterial strains, antibodies and chemical compounds in ex vivo infection settings. The use of fluorescently-labelled bacteria enables the concomitant detection of changes in bacterial growth. Using this method named CLIQ-BID (Cell Live Imaging Quantification of Bacteria Induced Damage), we were able to distinguish the virulence profiles of different pathogenic bacterial species and clinical strains.

Genome-Wide Analysis of the Response of Brucella melitensis NI to Polymyxin B

2020 ◽  
Vol 21 ◽  
Author(s):  
Zhen Wang ◽  
Jiawei Wang ◽  
Jie Cheng ◽  
Xiaowen Yang ◽  
Hai Jiang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Target Genes ◽  
Brucella Melitensis ◽  
Polymyxin B ◽  
Differentially Expressed ◽  
Cold Shock Protein ◽  
Genes Encoding

Background: The ability of pathogenic bacteria to survive antimicrobial peptides (AMPs) in various host niches may contribute to their virulence. Polymyxin B is a cationic AMP, and polymyxin drugs are considered to be the "last line of defense" in the clinical treatment of bacterial infections. Objective: The objectives of this study were to comprehensively study the response of Brucella melitensis strain NI to polymyxin B treatment and to identify the target genes in Brucella induced by polymyxin B stimulation. Methods: Following treatment with polymyxin B, differentially expressed genes in Brucella were detected using RNA-seq and validated using qRT-PCR. Results: In total, 874 differentially expressed genes were identified, including 560 up-regulated and 314 down-regulated genes. Functional annotation and KEGG pathway analysis revealed that many of these genes are involved in metabolism, two-component systems, transcriptional regulation, transport/membrane proteins, and virulence factors. Expression of genes involved in T4SS and flagellar biosynthesis and assembly, which are important virulence factors in Brucella, were upregulated by polymyxin B treatment. Discussion: Additionally, genes encoding the ABC transporters YejABEF and the cold-shock protein CspA were also upregulated. These genes confer resistance to AMPs and contribute to the virulence of Brucella. The NI∆sufC, NI∆sufD, NI∆ompW, NI∆exbB, NI∆tetR, and NI∆cspA mutants were also more sensitive than B. melitensis NI to polymyxin B. Conclusion: The results of this study provide important insights into the comprehensive response of Brucella in response to polymyxin B stimulation.

Diversity of Bacteria and Bacterial Products as Antibiofilm and Antiquorum Sensing Drugs Against Pathogenic Bacteria

2019 ◽  
Vol 20 (11) ◽  
pp. 1156-1179 ◽  
Author(s):  
Fazlurrahman Khan ◽  
Sandra Folarin Oloketuyi ◽  
Young-Mog Kim
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Extracellular Polymeric Substances ◽  
Bacterial Species ◽  
Cell Communication ◽  
Signaling Molecules ◽  
Extracellular Dna ◽  
Therapeutic Approaches ◽  
Metabolic Products ◽  
Biofilm Architecture

The increase in antibiotic resistance of pathogenic bacteria has led to the development of new therapeutic approaches to inhibit biofilm formation as well as interfere quorum sensing (QS) signaling systems. The QS system is a phenomenon in which pathogenic bacteria produce signaling molecules that are involved in cell to cell communication, production of virulence factors, biofilm maturation, and several other functions. In the natural environment, several non-pathogenic bacteria are present as mixed population along with pathogenic bacteria and they control the behavior of microbial community by producing secondary metabolites. Similarly, non-pathogenic bacteria also take advantages of the QS signaling molecule as a sole carbon source for their growth through catabolism with enzymes. Several enzymes are produced by bacteria which disrupt the biofilm architecture by degrading the composition of extracellular polymeric substances (EPS) such as exopolysaccharide, extracellular- DNA and protein. Thus, the interference of QS system by bacterial metabolic products and enzymatic catalysis, modification of the QS signaling molecules as well as enzymatic disruption of biofilm architecture have been considered as the alternative therapeutic approaches. This review article elaborates on the diversity of different bacterial species with respect to their metabolic products as well as enzymes and their molecular modes of action. The bacterial enzymes and metabolic products will open new and promising perspectives for the development of strategies against the pathogenic bacterial infections.

scholarly journals The family of bacterial ADP-ribosylating exotoxins.

1995 ◽  
Vol 8 (1) ◽  
pp. 34-47 ◽  
Author(s):  
K M Krueger ◽  
J T Barbieri
Keyword(s):  
Virulence Factors ◽  
Active Sites ◽  
Pathogenic Bacteria ◽  
Binding Proteins ◽  
Quaternary Structure ◽  
Amino Acid Homology ◽  
Gtp Binding Proteins ◽  
Gtp Binding ◽  
The Family ◽  
Primary Amino

Pathogenic bacteria utilize a variety of virulence factors that contribute to the clinical manifestation of their pathogenesis. Bacterial ADP-ribosylating exotoxins (bAREs) represent one family of virulence factors that exert their toxic effects by transferring the ADP-ribose moiety of NAD onto specific eucaryotic target proteins. The observations that some bAREs ADP-ribosylate eucaryotic proteins that regulate signal transduction, like the heterotrimeric GTP-binding proteins and the low-molecular-weight GTP-binding proteins, has extended interest in bAREs beyond the bacteriology laboratory. Molecular studies have shown that bAREs possess little primary amino acid homology and have diverse quaternary structure-function organization. Underlying this apparent diversity, biochemical and crystallographic studies have shown that several bAREs have conserved active-site structures and possess a conserved glutamic acid within their active sites.

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