scholarly journals Structure of the Potential Virulence Factor from Francisella tularensis Shows Unexpected Presence of the SHS2 Motif and Similarity to Other Bacterial Virulence Factors

2022 ◽  
Author(s):  
Janette Chammas ◽  
Mallika Iyer ◽  
George Minasov ◽  
Ludmilla Shuvalova ◽  
Wayne Anderson ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Francisella Tularensis ◽  
Virulence Factor ◽  
Pathogenic Bacteria ◽  
Large Family ◽  
Structural Motif ◽  
Dimensional Structure ◽  
Human Pathogens ◽  
Recognition Sequence ◽  
Potential Virulence Factor

Pathogenic bacteria attack their host by secreting virulence factors that in various ways interrupt host defenses and damage their cells. Functions of many virulence factors, even from well-studied pathogens, are still unknown. Francisella tularensis is a class A pathogen and a causative agent of tularemia, a disease that is lethal without proper treatment. Here we report the three-dimensional structure and preliminary analysis of the potential virulence factor identified by the transcriptomic analysis of the F. tularensis disease models that is encoded by the FTT_1539 gene. The structure of the FTT_1539 protein contains two sets of three stranded antiparallel beta sheets, with a helix placed between the first and the second beta strand in each sheet. This structural motif, previously seen in virulence factors from other pathogens, was named the SHS2 motif and identified to play a role in protein-protein interactions and small molecule recognition. Sequence and structure analysis identified FTT_1539 as a member of a large family of secreted proteins from a broad range of pathogenic bacteria, such as Helicobacter pylori and Mycobacterium tuberculosis. While the specific function of the proteins from this class is still unknown, their similarity to the H. pylori Tip-α protein that induces TNF-a and other chemokines through NF-kB activation suggests the existence of a common pathogen-host interference mechanism shared by multiple human pathogens.

scholarly journals The Secretion of Toxins and Other Exoproteins of Cronobacter: Role in Virulence, Adaption, and Persistence

2020 ◽  
Vol 8 (2) ◽  
pp. 229 ◽  
Author(s):  
Hyein Jang ◽  
Gopal R. Gopinath ◽  
Athmanya Eshwar ◽  
Shabarinath Srikumar ◽  
Scott Nguyen ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Human Disease ◽  
Pathogenic Bacteria ◽  
Eukaryotic Cell ◽  
Human Pathogens ◽  
Wide Range ◽  
Cell Processes ◽  
Cronobacter Species ◽  
Foodborne Pathogenic Bacteria ◽  
Species Specific

Cronobacter species are considered an opportunistic group of foodborne pathogenic bacteria capable of causing both intestinal and systemic human disease. This review describes common virulence themes shared among the seven Cronobacter species and describes multiple exoproteins secreted by Cronobacter, many of which are bacterial toxins that may play a role in human disease. The review will particularly concentrate on the virulence factors secreted by C. sakazakii, C. malonaticus, and C. turicensis, which are the primary human pathogens of interest. It has been discovered that various species-specific virulence factors adversely affect a wide range of eukaryotic cell processes including protein synthesis, cell division, and ion secretion. Many of these factors are toxins which have been shown to also modulate the host immune response. These factors are encoded on a variety of mobile genetic elements such as plasmids and transposons; this genomic plasticity implies ongoing re-assortment of virulence factor genes which has complicated our efforts to categorize Cronobacter into sharply defined genomic pathotypes.

scholarly journals A Metabolic Enzyme as a Primary Virulence Factor of Mycoplasma mycoides subsp. mycoides Small Colony

2005 ◽  
Vol 187 (19) ◽  
pp. 6824-6831 ◽  
Author(s):  
Paola Pilo ◽  
Edy M. Vilei ◽  
Ernst Peterhans ◽  
Laetitia Bonvin-Klotz ◽  
Michael H. Stoffel ◽  
...  
Keyword(s):  
Host Cell ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Pathogenic Bacteria ◽  
Cell Injury ◽  
Cell Damage ◽  
Metabolic Enzyme ◽  
Complex Interactions ◽  
Mycoplasma Mycoides ◽  
Small Colony

ABSTRACT During evolution, pathogenic bacteria have developed complex interactions with their hosts. This has frequently involved the acquisition of virulence factors on pathogenicity islands, plasmids, transposons, or prophages, allowing them to colonize, survive, and replicate within the host. In contrast, Mycoplasma species, the smallest self-replicating organisms, have regressively evolved from gram-positive bacteria by reduction of the genome to a minimal size, with the consequence that they have economized their genetic resources. Hence, pathogenic Mycoplasma species lack typical primary virulence factors such as toxins, cytolysins, and invasins. Consequently, little is known how pathogenic Mycoplasma species cause host cell damage, inflammation, and disease. Here we identify a novel primary virulence determinant in Mycoplasma mycoides subsp. mycoides Small Colony (SC), which causes host cell injury. This virulence factor, released in significant amounts in the presence of glycerol in the growth medium, consists of toxic by-products such as H2O2 formed by l-α-glycerophosphate oxidase (GlpO), a membrane-located enzyme that is involved in the metabolism of glycerol. When embryonic calf nasal epithelial cells are infected with M. mycoides subsp. mycoides SC in the presence of physiological amounts of glycerol, H2O2 is released inside the cells prior to cell death. This process can be inhibited with monospecific anti-GlpO antibodies.

scholarly journals Virulence Factor Genes Incidence among Enterococci from Sewage Sludge in Eastern Slovakia following Safety Aspect

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Andrea Lauková ◽  
Viola Strompfová ◽  
Jana Ščerbová ◽  
Monika Pogány Simonová
Keyword(s):  
Species Identification ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Pathogenic Bacteria ◽  
Health Hazard ◽  
Potential Health ◽  
Safety Aspect ◽  
Potential Health Hazard ◽  
Genus Identification ◽  
Virulence Factor Genes

The sewage sludges represent a potential health hazard because of the quantity of different microbiota detected in sewages. Among microbiota detected in sewages, also belong representatives of the phylum Firmicutes. In the past, environmental enterococci in addition to coliforms were widely used as indicators of faecal contamination. Regarding the enterococcal strains as potential pathogenic bacteria, their pathogenicity is mainly caused by production of virulence factors. Therefore, the aim of the study was to analyse incidence of virulence factors in enterococci from cows' dung water. Species identification of 24 enterococci using MALDI-TOF MS system allotted 23 strains to the species Enterococcus faecium with highly probable species identification and E. faecalis EEV20 with a score value meaning secure genus identification/probable species identification. Enterococci were absent of cytolysin A gene, hyaluronidase gene, and element IS gene. It can be concluded that they are not invasive which is very important from safety aspect. The most frequently detected gene was adhesin E. faecium (efaAfm, in 22 E. faecium strains and in one E. faecalis). Adhesin efaAfs gene was detected in E. faecalis EEV20 and in two E. faecium. GelE gene was present in three strains. E. faecium EF/EC31 was absent of virulence factor genes.

Virulence factors associated with organisms causing asymptomatic bacteriuria in pregnant females attending a tertiary care hospital

2017 ◽  
Vol 6 (05) ◽  
pp. 5373
Author(s):  
Prabha Ponnusamy* ◽  
Radhika Katragadda ◽  
Thyagarajan Ravinder
Keyword(s):  
Virulence Factors ◽  
Host Defense ◽  
Virulence Factor ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Asymptomatic Bacteriuria ◽  
Phenotypic Expression ◽  
Care Hospital ◽  
Cross Sectional ◽  
Pregnant Females

Asymptomatic bacteriuria (ASB), most common during pregnancy is endangering as it may lead to maternal and fetal complications. Various organisms causing ASB combats the host defense mechanisms through virulence factors exhibited by them. In order to understand the pathogenesis and sequelae of infections, virulence factors like hemolysin production, gelatinase production, haemagglutination, biofilm production and many more should be identified. Hence, we aimed at studying the distribution of virulence factors among each organism causing asymptomatic bacteriuria in pregnant females attending a tertiary care hospital. Materials and Methods: This cross-sectional study was conducted in Department of Microbiology over a period of one year and six months (January 2014 to June 2015) at a tertiary care teaching hospital. A total of 1000 urine samples were included in study taken from pregnant women with asymptomatic bacteriuria. Isolation, identification of organisms was done according to standard microbiological techniques and virulence factors for individual organisms by phenotypic method were tested. Results: Out of 1000 samples screened for ASB, organisms were isolated in following frequency distribution: Escherichia coli, the commonest 54/118 (45.76%), Klebsiella pneumoniae 21/118 (17.80%), Staphylococcus aureus 19/118 (16.10%), Staphylococcus saprophyticus 10/118 (8.45%), Enterococcus faecalis 9/118 (7.63%), Pseudomonas aeruginosa 3/118 (2.54%) and Proteus mirabilis 2/118 (1.69%). Virulence factors for individual organisms and biofilm detection for all organisms were done. Conclusion: Multifactorial mechanisms determine the pathogenicity of an organism and it needs to be explored by analyzing each virulence factor and mechanism of invasion in combating the host defense systems. Hence analyzing the phenotypic expression of each virulence factor helps in better understanding about the complications of ASB.

scholarly journals Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins

1993 ◽  
Vol 2 (3) ◽  
pp. 366-382 ◽  
Author(s):  
Miroslaw Cygler ◽  
Joseph D. Schrag ◽  
Joel L. Sussman ◽  
Michal Harel ◽  
Israel Silman ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Large Family ◽  
Sequence Conservation ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Related Proteins

scholarly journals TO STUDY THE ANTIBACTERIAL ACTIVITY OF VARIOUS EXTRACTS OF CLAUSENA DENTATA (WILLD.) ROEM.

2019 ◽  
pp. 69-73
Author(s):  
ANNAMALAI MADURAM ◽  
RAJU KAMARAJ
Keyword(s):  
Antibacterial Activity ◽  
Tamil Nadu ◽  
Pathogenic Bacteria ◽  
Volatile Oil ◽  
Stem Bark ◽  
Salmonella Typhi ◽  
Chloroform Extract ◽  
Klebsiella Pneumonia ◽  
Human Pathogens ◽  
Human Pathogenic Bacteria

Objectives: The objectives of the study were to study the antibacterial activity for the various extracts of Clausena dentata against human pathogens. Clausena (Rutaceae) is a genus of about 23 species of unarmed trees and shrubs. The stem bark of C. dentata is used in veterinary medicine for the treatment of wounds and sprains. Even though C. dentata has a lot of potential medical uses, the study of microbiological properties is very scarce. Methods: The plant C. dentata was collected from Kadagaman, near Tiruvannamalai, Tamil Nadu, India, and authenticated by Centre for Advanced Study in Botany, University of Madras, Chennai. The dry powder of stem bark was extracted with hexane, chloroform, and methanol. The extracts were subjected to qualitative phytochemical screening and antibacterial activity against human pathogenic bacteria such as Escherichia coli, Salmonella Typhi, Klebsiella pneumonia, Vibrio cholerae, and Staphylococcus aureus and compared with ciprofloxacin. Results: Qualitative chemical tests revealed the presence of various phytochemicals such as alkaloids, glycosides, carbohydrate, proteins and amino acids, phytosterols, and volatile oil. The antibacterial activity result reveals that all the extracts were are more active against V. cholerae. The activity against Pseudomonas aeruginosa was mild. Conclusion: The activity against V. cholerae was comparable with that of 5 μg/mL ciprofloxacin at the concentration of C. dentata 40 μg/mL. The orders of antibacterial activity against human pathogenic bacteria are hexane, methanol, and chloroform extract of C. dentata.

scholarly journals Antimicrobial Activities of Marine Sponge-Associated Bacteria

2021 ◽  
Vol 9 (1) ◽  
pp. 171
Author(s):  
Yitayal S. Anteneh ◽  
Qi Yang ◽  
Melissa H. Brown ◽  
Christopher M. M. Franco
Keyword(s):  
Pathogenic Bacteria ◽  
South Australia ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Marine Sponges ◽  
Bioactive Metabolites ◽  
Human Pathogens ◽  
Sponge Associated Bacteria ◽  
Microbial Symbionts ◽  
Bacteria And Fungi

The misuse and overuse of antibiotics have led to the emergence of multidrug-resistant microorganisms, which decreases the chance of treating those infected with existing antibiotics. This resistance calls for the search of new antimicrobials from prolific producers of novel natural products including marine sponges. Many of the novel active compounds reported from sponges have originated from their microbial symbionts. Therefore, this study aims to screen for bioactive metabolites from bacteria isolated from sponges. Twelve sponge samples were collected from South Australian marine environments and grown on seven isolation media under four incubation conditions; a total of 1234 bacterial isolates were obtained. Of these, 169 bacteria were tested in media optimized for production of antimicrobial metabolites and screened against eleven human pathogens. Seventy bacteria were found to be active against at least one test bacterial or fungal pathogen, while 37% of the tested bacteria showed activity against Staphylococcus aureus including methicillin-resistant strains and antifungal activity was produced by 21% the isolates. A potential novel active compound was purified possessing inhibitory activity against S. aureus. Using 16S rRNA, the strain was identified as Streptomyces sp. Our study highlights that the marine sponges of South Australia are a rich source of abundant and diverse bacteria producing metabolites with antimicrobial activities against human pathogenic bacteria and fungi.

scholarly journals Discovery of uncompetitive inhibitors of SapM that compromise intracellular survival of Mycobacterium tuberculosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulina Fernández-Soto ◽  
Joshua Casulli ◽  
Danilo Solano-Castro ◽  
Pablo Rodríguez-Fernández ◽  
Thomas A. Jowitt ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Francisella Tularensis ◽  
Virulence Factor ◽  
Chemical Properties ◽  
Full Potential ◽  
Mechanism Of Inhibition ◽  
Physico Chemical ◽  
Microbial Infections ◽  
Mechanism Of Catalysis ◽  
Antivirulence Agents

AbstractSapM is a secreted virulence factor from Mycobacterium tuberculosis critical for pathogen survival and persistence inside the host. Its full potential as a target for tuberculosis treatment has not yet been exploited because of the lack of potent inhibitors available. By screening over 1500 small molecules, we have identified new potent and selective inhibitors of SapM with an uncompetitive mechanism of inhibition. The best inhibitors share a trihydroxy-benzene moiety essential for activity. Importantly, the inhibitors significantly reduce mycobacterial burden in infected human macrophages at 1 µM, and they are selective with respect to other mycobacterial and human phosphatases. The best inhibitor also reduces intracellular burden of Francisella tularensis, which secretes the virulence factor AcpA, a homologue of SapM, with the same mechanism of catalysis and inhibition. Our findings demonstrate that inhibition of SapM with small molecule inhibitors is efficient in reducing intracellular mycobacterial survival in host macrophages and confirm SapM as a potential therapeutic target. These initial compounds have favourable physico-chemical properties and provide a basis for exploration towards the development of new tuberculosis treatments. The efficacy of a SapM inhibitor in reducing Francisella tularensis intracellular burden suggests the potential for developing broad-spectrum antivirulence agents to treat microbial infections.

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