scholarly journals PathFams: statistical detection of pathogen-associated protein domains

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Briallen Lobb ◽  
Benjamin Jean-Marie Tremblay ◽  
Gabriel Moreno-Hagelsieb ◽  
Andrew C. Doxey

Abstract Background A substantial fraction of genes identified within bacterial genomes encode proteins of unknown function. Identifying which of these proteins represent potential virulence factors, and mapping their key virulence determinants, is a challenging but important goal. Results To facilitate virulence factor discovery, we performed a comprehensive analysis of 17,929 protein domain families within the Pfam database, and scored them based on their overrepresentation in pathogenic versus non-pathogenic species, taxonomic distribution, relative abundance in metagenomic datasets, and other factors. Conclusions We identify pathogen-associated domain families, candidate virulence factors in the human gut, and eukaryotic-like mimicry domains with likely roles in virulence. Furthermore, we provide an interactive database called PathFams to allow users to explore pathogen-associated domains as well as identify pathogen-associated domains and domain architectures in user-uploaded sequences of interest. PathFams is freely available at https://pathfams.uwaterloo.ca.

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Yu Pan ◽  
Jiaxiong Zeng ◽  
Liguan Li ◽  
Jintao Yang ◽  
Ziyun Tang ◽  
...  

ABSTRACT Widespread use of antibiotics has enhanced the evolution of highly resilient pathogens and poses a severe risk to human health via coselection of antibiotic resistance genes (ARGs) and virulence factors (VFs). In this study, we rigorously evaluate the abundance relationship and physical linkage between ARGs and VFs by performing a comprehensive analysis of 9,070 bacterial genomes isolated from multiple species and hosts. The coexistence of ARGs and VFs was observed in bacteria across distinct phyla, pathogenicities, and habitats, especially among human-associated pathogens. The coexistence patterns of gene elements in different habitats and pathogenicity groups were similar, presumably due to frequent gene transfer. A shorter intergenic distance between mobile genetic elements and ARGs/VFs was detected in human/animal-associated bacteria, indicating a higher transfer potential. Increased accumulation of exogenous ARGs/VFs in human pathogens highlights the importance of gene acquisition in the evolution of human commensal bacteria. Overall, the findings provide insights into the genic features of combinations of ARG-VF and expand our understanding of ARG-VF coexistence in bacteria. IMPORTANCE Antibiotic resistance has become a serious global health concern. Despite numerous case studies, a comprehensive analysis of ARG and VF coexistence in bacteria is lacking. In this study, we explore the coexistence profiles of ARGs and VFs in diverse categories of bacteria by using a high-resolution bioinformatics approach. We also provide compelling evidence of unique ARG-VF gene pairs coexisting in specific bacterial genomes and reveal the potential risk associated with the coexistence of ARGs and VFs in organisms in both clinical settings and environments.


2012 ◽  
Vol 6 (1) ◽  
pp. 14-17
Author(s):  
Jabin Akhter ◽  
Shaheda Anwar ◽  
Sharmeen Ahmed

Urinary tract infection caused by Enterococci has become frequent occurrences in health care settings. Currently they emerged with increasing resistance to multiple antibiotics.  Haemolysin, gelatinase and biofilm production are some markers that have been proposed as possible Enterococcal virulence factors. In view of the increasing importance of Enterococcal infection, the present study was designed to isolate and identify the Enterococci to the species level from urine of urinary tract infection patients and to investigate their possible virulence factors. Biofilm was detected on polystyrene microtitre plate to see the adherence of microorganism. Haemolysin production and gelatin hydrolysis detected by standard microbiological method. Fifty nine enterococcal isolates were speciated by conventional microbiological method and examined for their ability to form biofilm by microtitre plate assay. In this study, biofilm formations by Enterococci were found in 83.33% isolates from catheterized and 56.09% from non-catheterized patients. Aong them, E.faecalis & 50% E.faecium produced biofilm. About 43.63% E.faecalis & 10% E.faecium produced haemolysin and only one isolate were found to be gelatinase positive. Frequency of virulence factors (VFs) in combination was observed in this study. Two VFs (haemolysin and biofilm) were observed in 27.11% in combination and 3 VFs ( haemolysinm biofilm and gelatinase) were present in 1.69% isolates. These results suggest that although there may not be an absolute role for individual virulence determinants in infectivity, combinations of factors may play a role in allowing a biofilm infection to be more resistant to therapy.DOI: http://dx.doi.org/10.3329/bjmm.v6i1.19361 Bangladesh J Med Microbiol 2012; 06(01): 14-17


Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 712-723 ◽  
Author(s):  
Valérie Dekimpe ◽  
Eric Déziel

Pseudomonas aeruginosa uses the two major quorum-sensing (QS) regulatory systems las and rhl to modulate the expression of many of its virulence factors. The las system is considered to stand at the top of the QS hierarchy. However, some virulence factors such as pyocyanin have been reported to still be produced in lasR mutants under certain conditions. Interestingly, such mutants arise spontaneously under various conditions, including in the airways of cystic fibrosis patients. Using transcriptional lacZ reporters, LC/MS quantification and phenotypic assays, we have investigated the regulation of QS-controlled factors by the las system. Our results show that activity of the rhl system is only delayed in a lasR mutant, thus allowing the expression of multiple virulence determinants such as pyocyanin, rhamnolipids and C4-homoserine lactone (HSL) during the late stationary phase. Moreover, at this stage, RhlR is able to overcome the absence of the las system by activating specific LasR-controlled functions, including production of 3-oxo-C12-HSL and Pseudomonas quinolone signal (PQS). P. aeruginosa is thus able to circumvent the deficiency of one of its QS systems by allowing the other to take over. This work demonstrates that the QS hierarchy is more complex than the model simply presenting the las system above the rhl system.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jasmine Martinez ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Robert Courville ◽  
Camila Pimentel ◽  
...  

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.


2006 ◽  
Vol 188 (8) ◽  
pp. 3088-3098 ◽  
Author(s):  
Balakrishnan Venkatesh ◽  
Lavanya Babujee ◽  
Hui Liu ◽  
Pete Hedley ◽  
Takashi Fujikawa ◽  
...  

ABSTRACT The PhoPQ two-component system regulates virulence factors in Erwinia chrysanthemi, a pectinolytic enterobacterium that causes soft rot in several plant species. We characterized the effect of a mutation in phoQ, the gene encoding the sensor kinase PhoQ of the PhoPQ two-component regulatory system, on the global transcriptional profile of E. chrysanthemi using cDNA microarrays and further confirmed our results by quantitative reverse transcription-PCR analysis. Our results indicate that a mutation in phoQ affects transcription of at least 40 genes, even in the absence of inducing conditions. Enhanced expression of several genes involved in iron metabolism was observed in the mutant, including that of the acs operon that is involved in achromobactin biosynthesis and transport. This siderophore is required for full virulence of E. chrysanthemi, and its expression is governed by the global repressor protein Fur. Changes in gene expression were also observed for membrane transporters, stress-related genes, toxins, and transcriptional regulators. Our results indicate that the PhoPQ system governs the expression of several additional virulence factors and may also be involved in interactions with other regulatory systems.


2011 ◽  
Vol 56 (No. 7) ◽  
pp. 352-357 ◽  
Author(s):  
K. Trivedi ◽  
S. Cupakova ◽  
R. Karpiskova

A collection of 250 enterococci isolated from various food-stuffs were used to investigate seven virulence determinants and the microbial susceptibility of eight antibiotics. Species-specific PCR revealed the presence of E. faecalis (127 isolates), E. faecium (77 isolates), E. casseliflavus (21 isolates), E. mundtii (19 isolates) and E. durans (six isolates). Multiplex PCR for virulence factors showed that from a total 250 isolates, 221 (88.4%) carried one or more virulence-encoding genes. β-Haemolytic activity was also evident in enterococcal species other than E. faecalis and E. faecium. Species other than E. faecalis and E. faecium isolated from food are also seen to harbour the potential for virulence. Antimicrobial susceptibility testing using the disk diffusion method showed that of the total 250 isolates, 114 (46%) were resistant to cephalothin and 94 (38%) to ofloxacin. Lower antibiotic resistance was seen with ampicillin, chloramphenicol, gentamicin and teicoplanin. None of the isolates was found to be resistant to vancomycin. The results of this study show that food can play an important role in the spread of enterococci with virulence potential through the food chain to the human population.


2019 ◽  
Vol 47 (1) ◽  
pp. 389-398 ◽  
Author(s):  
Kira S. Makarova ◽  
Yuri I. Wolf ◽  
Eugene V. Koonin

Abstract A substantial fraction of archaeal genes, from ∼30% to as much as 80%, encode ‘hypothetical' proteins or genomic ‘dark matter'. Archaeal genomes typically contain a higher fraction of dark matter compared with bacterial genomes, primarily, because isolation and cultivation of most archaea in the laboratory, and accordingly, experimental characterization of archaeal genes, are difficult. In the present study, we present quantitative characteristics of the archaeal genomic dark matter and discuss comparative genomic approaches for functional prediction for ‘hypothetical' proteins. We propose a list of top priority candidates for experimental characterization with a broad distribution among archaea and those that are characteristic of poorly studied major archaeal groups such as Thaumarchaea, DPANN (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota and Nanohaloarchaeota) and Asgard.


2008 ◽  
Vol 57 (4) ◽  
pp. 403-410 ◽  
Author(s):  
P. Sauer ◽  
J. Síla ◽  
T. Štosová ◽  
R. Večeřová ◽  
P. Hejnar ◽  
...  

A rather fast and complicated progression of an infection caused by some strains of Staphylococcus aureus could be associated with the expression and co-action of virulence factor complexes in these strains. This study screened the antibiotic susceptibility and prevalence of virulence markers in isolates of meticillin-resistant S. aureus (MRSA) obtained from patients hospitalized at the University Hospital in Olomouc, Czech Republic. A total of 100 isolates was screened for 13 genes encoding extracellular virulence determinants (tst, pvl, eta, etb, sea, seb, sec, sed, see, seg, seh, sei and sej) and for their distribution in sample types. Eighty-nine isolates were positive for at least one of the genes. Genes for etb, pvl, see and seh were not detected in any of the MRSA isolates. No statistically significant differences in the occurrence of the determinants studied among sample types were found.


mSystems ◽  
2016 ◽  
Vol 1 (6) ◽  
Author(s):  
Aaron Weimann ◽  
Kyra Mooren ◽  
Jeremy Frank ◽  
Phillip B. Pope ◽  
Andreas Bremges ◽  
...  

ABSTRACT Bacteria are ubiquitous in our ecosystem and have a major impact on human health, e.g., by supporting digestion in the human gut. Bacterial communities can also aid in biotechnological processes such as wastewater treatment or decontamination of polluted soils. Diverse bacteria contribute with their unique capabilities to the functioning of such ecosystems, but lab experiments to investigate those capabilities are labor-intensive. Major advances in sequencing techniques open up the opportunity to study bacteria by their genome sequences. For this purpose, we have developed Traitar, software that predicts traits of bacteria on the basis of their genomes. It is applicable to studies with tens or hundreds of bacterial genomes. Traitar may help researchers in microbiology to pinpoint the traits of interest, reducing the amount of wet lab work required. The number of sequenced genomes is growing exponentially, profoundly shifting the bottleneck from data generation to genome interpretation. Traits are often used to characterize and distinguish bacteria and are likely a driving factor in microbial community composition, yet little is known about the traits of most microbes. We describe Traitar, the microbial trait analyzer, which is a fully automated software package for deriving phenotypes from a genome sequence. Traitar provides phenotype classifiers to predict 67 traits related to the use of various substrates as carbon and energy sources, oxygen requirement, morphology, antibiotic susceptibility, proteolysis, and enzymatic activities. Furthermore, it suggests protein families associated with the presence of particular phenotypes. Our method uses L1-regularized L2-loss support vector machines for phenotype assignments based on phyletic patterns of protein families and their evolutionary histories across a diverse set of microbial species. We demonstrate reliable phenotype assignment for Traitar to bacterial genomes from 572 species of eight phyla, also based on incomplete single-cell genomes and simulated draft genomes. We also showcase its application in metagenomics by verifying and complementing a manual metabolic reconstruction of two novel Clostridiales species based on draft genomes recovered from commercial biogas reactors. Traitar is available at https://github.com/hzi-bifo/traitar . IMPORTANCE Bacteria are ubiquitous in our ecosystem and have a major impact on human health, e.g., by supporting digestion in the human gut. Bacterial communities can also aid in biotechnological processes such as wastewater treatment or decontamination of polluted soils. Diverse bacteria contribute with their unique capabilities to the functioning of such ecosystems, but lab experiments to investigate those capabilities are labor-intensive. Major advances in sequencing techniques open up the opportunity to study bacteria by their genome sequences. For this purpose, we have developed Traitar, software that predicts traits of bacteria on the basis of their genomes. It is applicable to studies with tens or hundreds of bacterial genomes. Traitar may help researchers in microbiology to pinpoint the traits of interest, reducing the amount of wet lab work required.


2017 ◽  
Vol 61 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Joanna Kołsut ◽  
Paulina Borówka ◽  
Błażej Marciniak ◽  
Ewelina Wójcik ◽  
Arkadiusz Wojtasik ◽  
...  

AbstractIntroduction: Colibacillosis – the most common disease of poultry, is caused mainly by avian pathogenic Escherichia coli (APEC). However, thus far, no pattern to the molecular basis of the pathogenicity of these bacteria has been established beyond dispute. In this study, genomes of APEC were investigated to ascribe importance and explore the distribution of 16 genes recognised as their virulence factors.Material and Methods: A total of 14 pathogenic for poultry E. coli strains were isolated, and their DNA was sequenced, assembled de novo, and annotated. Amino acid sequences from these bacteria and an additional 16 freely available APEC amino acid sequences were analysed with the DIFFIND tool to define their virulence factors.Results: The DIFFIND tool enabled quick, reliable, and convenient assessment of the differences between compared amino acid sequences from bacterial genomes. The presence of 16 protein sequences indicated as pathogenicity factors in poultry resulted in the generation of a heatmap which categorises genomes in terms of the existence and similarity of the analysed protein sequences.Conclusion: The proposed method of detection of virulence factors using the capabilities of the DIFFIND tool may be useful in the analysis of similarities of E. coli and other sequences deriving from bacteria. Phylogenetic analysis resulted in reliable segregation of 30 APEC strains into five main clusters containing various virulence associated genes (VAGs).


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