Source: http://www.asmscience.org/content/concept/Entity/ASM/Microbiology/Bacteria_and_Archaea/Bacteria/Bacterial_Pathogenesis/Bacterial_Virulence_Factors
Timestamp: 2019-04-21 16:49:24+00:00

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Enterotoxigenic Escherichia coli (ETEC) is the most common cause of E. coli diarrhea in farm animals. ETEC are characterized by the ability to produce two types of virulence factors: adhesins that promote binding to specific enterocyte receptors for intestinal colonization and enterotoxins responsible for fluid secretion. The best-characterized adhesins are expressed in the context of fimbriae, such as the F4 (also designated K88), F5 (K99), F6 (987P), F17, and F18 fimbriae. Once established in the animal small intestine, ETEC produce enterotoxin(s) that lead to diarrhea. The enterotoxins belong to two major classes: heat-labile toxins that consist of one active and five binding subunits (LT), and heat-stable toxins that are small polypeptides (STa, STb, and EAST1). This review describes the disease and pathogenesis of animal ETEC, the corresponding virulence genes and protein products of these bacteria, their regulation and targets in animal hosts, as well as mechanisms of action. Furthermore, vaccines, inhibitors, probiotics, and the identification of potential new targets by genomics are presented in the context of animal ETEC.
Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because Escherichia coli represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in E. coli strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of E. coli causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain E. coli might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that E. coli needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to E. coli strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic E. coli may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain.
Phage predation can shape bacterial populations in patients and in other environments, reducing the virulence of particular bacterial pathogens, according to several researchers who spoke during the 2015 ICAAC, held in San Diego last September. They described phages that target bacterial virulence factors, forcing the selection of bacterial mutants that are highly attenuated and easily eradicated by the host. These findings may lead to phage-based public health strategies to prevent and control disease outbreaks, and to more effective treatments for individual patients with bacterial infections.
Enterohemorrhagic Escherichia coli (EHEC) is a highly pathogenic bacterial strain capable of causing watery or bloody diarrhea, the latter termed hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is defined as the simultaneous development of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The mechanism by which EHEC bacteria colonize and cause severe colitis, followed by renal failure with activated blood cells, as well as neurological symptoms, involves the interaction of bacterial virulence factors and specific pathogen-associated molecular patterns with host cells as well as the host response. The innate immune host response comprises the release of antimicrobial peptides as well as cytokines and chemokines in addition to activation and/or injury to leukocytes, platelets, and erythrocytes and activation of the complement system. Some of the bacterial interactions with the host may be protective in nature, but, when excessive, contribute to extensive tissue injury, inflammation, and thrombosis, effects that may worsen the clinical outcome of EHEC infection. This article describes aspects of the host response occurring during EHEC infection and their effects on specific organs.
Review of: Clinical Microbiology Made Ridiculously Simple, 5th ed.; Mark Gladwin and William Trattler; (2011). MedMaster Inc., Miami, FL. 400 pages.
Bioinformatics, the use of computer resources to understand biological information, is an important tool in research, and can be easily integrated into the curriculum of undergraduate courses. Such an example is provided in this series of four activities that introduces students to the field of bioinformatics as they design PCR based tests for pathogenic E. coli strains. A variety of computer tools are used including BLAST searches at NCBI, bacterial genome searches at the Integrated Microbial Genomes (IMG) database, protein analysis at Pfam and literature research at PubMed. In the process, students also learn about virulence factors, enzyme function and horizontal gene transfer. Some or all of the four activities can be incorporated into microbiology or general biology courses taken by students at a variety of levels, ranging from high school through college. The activities build on one another as they teach and reinforce knowledge and skills, promote critical thinking, and provide for student collaboration and presentation. The computer-based activities can be done either in class or outside of class, thus are appropriate for inclusion in online or blended learning formats. Assessment data showed that students learned general microbiology concepts related to pathogenesis and enzyme function, gained skills in using tools of bioinformatics and molecular biology, and successfully developed and tested a scientific hypothesis.
Human salmonellosis is generally associated with Salmonella enterica from subspecies enterica (subspecies I). Acute infections can present in one of four ways: enteric fever, gastroenteritis, bacteremia, or extraintestinal focal infection. As with other infectious diseases, the course and outcome of the infection depend on a variety of factors, including the infecting organism, the inoculating dose, and the immune status and genetic background of the host. For serovarsTyphi and Paratyphi A there is a clear association between the genetic background of the serovar and systemic infection in humans. For serovars Paratyphi B and Paratyphi C, a good clinical description of the host and detailed population genetics of the pathogen are necessary before more detailed genetic studies of novel virulence factors,or host factors,can be initiated. For the nontyphoidalserovars (NTS) the situation is less clear. Serovars Typhimurium and Enteritidis are the most common within the food chain, and so the large number of invasive infections associated with these serovars is most likely due to exposure rather than to increased virulence of the pathogen. In Africa, however, a closely related group of strains of serovar Typhimurium, associated with HIV infection, may have become host adapted tohumans, suggesting that not all isolates called "Typhimurium" should be considered as a single group. Here we review current knowledge of the salmonellae for which invasive disease in humans is an important aspect of their population biology.
Vibrio vulnificus, a gram-negative marine bacterium, has been recognized as an important pathogen of both humans and eels for decades. V. vulnificus infection is characterized by the rapid spread of this organism from intestine or skin into deeper tissue and even the bloodstream to result in septicemia and/or necrotic skin lesions. One of gene regions, region XII, was found to be associated with one of the two lineages of V. vulnificus divided based on the multilocus sequence typing (MLST) data of six housekeeping genes. The superintegron is unique to each Vibrio species, containing different kinds of gene cassettes. The functions of gene cassettes and open reading frames (ORFs) in superintegrons remain largely unknown. The publication of nucleotide sequences of two BT1 V. vulnificus genomes and the BT2 virulence plasmid has opened up opportunities for mining new virulence genes for mice and eels as well as developing new diagnostic methods. Moreover, the complete genome information can be applied to epidemiology study and food safety monitoring. Because of the high mortality rate of systemic infection with V. vulnificus, an effective vaccine against this organism is desired, particularly for individuals at high risk. Contaminated bivalve molluscan shellfish, including oysters, clams, and mussels, are major sources of per os infection by V. vulnificus. The vast information generated from the genomes of major representative Vibrio species has enabled comparative analysis and provided an opportunity to investigate the biology of this group of marine bacteria.
It is expected that the increasing genetic information on Bacillus cereus in genome databases will pave the way for investigating its evolution, ecology, and virulence, and, finally, will contribute to the development of new strategies to control and prevent foodborne diseases caused by B. cereus. This chapter talks about toxins and population structure of the B.cereus group. Many bacterial genome sequences, including B. cereus strains, are available in draft versions only and are missing a few percent of the sequence. The chapter deals with only complete genome sequences, and illustrates that species definition in the B. cereus group remains an open question and it may well be that the discussion will gain momentum with daily growing genome information, especially of "borderline strains". It focuses on pan genome, core genome, accessory genome, and mobilome of the B. cereus group. B. cereus geomics suggest that the mobilome of this species group is important not only to model its evolution, but also to differentiate and detect the different pathotypes. It is clearly visible that the high number of B. anthracis and B. cereus strains already known is improving research tools to study pathogenicity, ecology, and host and environmental adaptation.
The autotransporter and two-partner secretion (TPS) pathways are used by E. coli and many other Gram-negative bacteria to delivervirulence factors into the extracellular milieu.Autotransporters arecomprised of an N-terminal extracellular ("passenger") domain and a C-terminal β barrel domain ("β domain") that anchors the protein to the outer membrane and facilitates passenger domain secretion. In the TPS pathway, a secreted polypeptide ("exoprotein") is coordinately expressed with an outer membrane protein that serves as a dedicated transporter. Bothpathways are often grouped together under the heading "type V secretion" because they have many features in common and are used for the secretion of structurally related polypeptides, but it is likely that theyhave distinct evolutionary origins. Although it was proposed many years ago that autotransporterpassenger domains are transported across the outer membrane through a channel formed by the covalently linked β domain, there is increasing evidence that additional factors are involved in the translocation reaction. Furthermore, details of the mechanism of protein secretion through the TPS pathway are only beginning to emerge. In this chapter I discussour current understanding ofboth early and late steps in the biogenesis of polypeptides secreted through type V pathways and current modelsofthe mechanism of secretion.
This chapter presents an overview of the interaction of Campylobacter jejuni with intestinal host cells and focuses on bacterial adherence and invasion into the intestinal epithelium, transcytosis across the epithelial mucosa, and ensuing damage to host cells. Campylobacter invasion into the epithelial mucosa appears to be an essential process leading to colitis. Although many researchers would agree with this general summary of Campylobacter invasion events, there still remains considerable confusion regarding how Campylobacter enter and cross the intestinal mucosa. In fact, researchers concluded, after treating T-84 cells with EGTA, that CadF-dependent invasion of epithelial cells occurs preferentially at the basolateral surface, which normally interacts with fibronectin. In the above study, the number of internalized C. jejuni F38011 increased approximately threefold after EGTA treatment and was then reduced ~80% by treating with anti-fibronectin antibody. A common theme among pathogenic invasive microorganisms is their ability to usurp the eukaryotic cell signaling systems both to allow for invasion and to trigger disease pathogenesis. The current data on signal transduction events involved in C. jejuni invasion suggest that host cell ‘’invasion receptors’’ reside in filipin III-sensitive membrane microdomains (i.e., lipid rafts). Clinical infections, experimental infections in humans and animals, and in vitro analyses in cultured human cells have now clearly demonstrated that cell adherence and invasiveness are necessary steps in Campylobacter-induced inflammatory diarrhea. Much progress has been made in the past 10 years in the understanding of the cell biology of these events.
A clear etiological link has been established between infection with several gram-negative enteric pathogens, including Salmonella spp., and the incidence of reactive arthritis (ReA), an autoimmune disease that largely affects the joints. ReA is sometimes referred to as Reiter&apos;s syndrome, particularly when accompanied by uveitis and urethritis. This review reviews the evidence etiologically linking Salmonella infection with autoimmune disease and addresses the roles that bacterial and host elements play in controlling disease outcome. ReA is an autoimmune disease that largely consists of painful joint inflammation but also can include inflammation of the eye, gastrointestinal tract, and skin. ReA is a member of a broad spectrum of chronic inflammatory disorders termed the seronegative spondyloarthropathies (SNSpAs) that includes ankylosing spondylitis (AS), psoriatic arthritis, and enteropathic arthritis. Salmonella species, as well as other enteric pathogens associated with postgastroenteritis ReA, are facultative intracellular gram-negative bacteria. Many studies have analyzed the association of the HLA class I molecule, HLA-B27, with SNSpAs. Whereas B27 has been shown to be present in 90 to 95% of cases of AS, the association of the B27 haplotype with other SNSpAs is more tenuous. The clear association between ReA and infection with Salmonella or other gram-negative enteric pathogens has led to the suggestion that the adaptive immune response to infection has an autoimmune component. In addition to various Salmonella species, other gram-negative enteric pathogens have been linked to the development of ReA. Given their close relationship to Salmonella, this review considers the involvement of Shigella species in ReA.
An interesting facet of Streptococcus pyogenes and Staphylococcus aureus, is their double role as commensals and pathogens. In this context, certain aspects of bacterial pathogenicity can be interpreted as a recall of antipredation strategies that bacteria evolved against phagocytosis by protozoan grazers. Many bacteria contain multiple genomes of bacterial viruses in their chromosomes. Prophage DNA can constitute a sizable part of the total bacterial DNA. When genomes from closely related bacteria were compared in a dot plot analysis, prophage sequences frequently accounted for a substantial, if not major, part of the differences between the genomes. Prophages can be present in many different forms, ranging from inducible prophages via prophages showing deletions, insertion, and rearrangements, to prophage remnants that lost most of the phage genome. In prophages from gram-negative bacteria, “extra” genes were identified near both prophage DNA ends. Prophages seem to be only transient passengers on the bacterial chromosomes, at least when seen on an evolutionary timescale. In an appealing model, the emergence of new, unusually virulent subclones of M3 strains is explained by the sequential acquisition of prophages, suggesting bacterial pathogenicity evolution in the fast lane. The virulence genes have certainly not evolved in phages but are the result of close bacterial interaction with the eukaryotic cell. Phages are perhaps only the handy gene carriers efficiently shuttling genes around in the bacterial world.
In the developing world, Streptococcus pneumoniae is a major cause of pneumonia in young children, and the total worldwide mortality due to pneumococcal infections is approximately 1 to 2 million per year. The capsule is an integral part of the pneumococcal cell surface. The S. pneumoniae type 3 polysaccharide, as discussed, is not linked to the peptidoglycan but remains cell associated via a membrane lipid linkage or interactions with a membrane protein involved in its synthesis. The synthesis of all polysaccharides begins with the synthesis of nucleotide precursor sugars in the cytoplasm. Global control pathways affecting carbon metabolism may also be involved in the regulation of capsule synthesis. In particular, catabolite control protein A (CcpA) is an important regulator of the phosphoenolpyruvate-dependent phosphotransferase system that is the major system for sugar uptake in many bacteria. A mechanism for cleaving the chain has not been demonstrated but is predicted to be enzymatic based on the inability to introduce mechanical breaks without using sonication. The release of capsular polysaccharide may be important in pathogenesis, and the identification of an enzyme involved in this process will be an important step in understanding this role. Analyses of the genetics and biosynthesis of capsule production have yielded many important insights into one of the most important bacterial virulence factors. Understanding the regulatory mechanisms involved in capsule synthesis and release, and their integration with the synthesis of other surface structures, will thus be an important step in understanding the overall metabolism and virulence of the cell.
The prevailing paradigm of bacterial evolution is clonal descent with periodic modification, punctuated with discrete occurrences of horizontal genetic transmission. This latter phenomenon, termed "mosaicism," is reported with increasing frequency among bacterial toxins. Toxins are generally thought to execute one of two principal pathogenic functions: host avoidance and host damage. However, a prominent theme of bacterial toxin research in the last decade is the identification of multiple patho-genetic functions for bacterial toxins. In terms of evolution, it may be most efficient to adopt virulence factors from another pathogenic organism or to embue an existing one with additional functions. It should be noted that, of the extant STa molecules, none is clearly primative in the evolutionary sense, yet it is interesting to note that, like guanylin, EAST-1 contains four cysteine residues, rather than the six present in STaH and STaP. The typical RTX toxin is encoded by a four-gene operon comprising, in order, the modifying enzyme, the toxin structural gene, and the two components of the secretion system. The accessory genes are highly conserved among the RTX toxins, whereas there is substantial diversity among the toxin structural genes. The fundamental mechanisms of bacterial evolution operate on toxin genes as they do on all genetic loci.
Vibriosis is one of the most prevalent fish diseases caused by bacteria belonging to the genus Vibrio. Vibriosis caused by Vibrio anguillarum has been particularly devastating in the marine culture of salmonid fish. The correlation between serotype and virulence may reflect the ability of the bacterial surface antigens to interact with the host tissues. The ferric-anguibactin receptor FatA is an 86-kDa protein that is essential for anguibactin transport. The FatA amino acid sequence is similar to other receptors involved in iron transport, e.g., FhuA and FepA of Escherichia coli, and a TonB box can be identified at its amino-terminal end. V. ordalii causes vibriosis in wild and cultured marine salmonids in the Pacific Northwest of the United States and Japan. The determination and analysis of the complete nucleotide sequence could provide information about the role of pMJ101 in the pathobiology of this fish pathogen. Juvenile salmon exposed to V. ordalii by parenteral challenge developed a systemic infection, and the bacterium was recovered from liver, kidneys, spleen, and blood immediately after the infection. However, the number of bacteria in the liver declined after 1 h and then increased 22 h after infection; bacterial numbers were high in all the organs, and 100% mortality occurred 6 days after infection. The latter observations demonstrate that artificial infection of juvenile salmon is a valid experimental model to study the mechanisms and the bacterial virulence factors involved in the pathogenesis of the infections caused by V. ordalii.
The first described adhesive antigen of Escherichia coli strains isolated from animals was the K88 antigen, expressed by strains from diarrheic pigs. The K88 antigen was visible by electron microscopy as a surface-exposed filament that was thin and flexible and had hemagglutinating properties. Many different fimbriae have been identified in animal enterotoxigenic E. coli (ETEC) and have been discussed in this article. The role of these fimbriae in the pathogenesis of ETEC has been best studied with K88, K99, 987P, and F41. Each fimbrial type carries at least one adhesive moiety that is specific for a certain host receptor, determining host species, age, and tissue specificities. ETEC are the most frequently diagnosed pathogens among neonatal and post-weaning piglets that die of diarrhea. Immune electron microscopy of animal ETEC fimbriae usually shows that the minor subunits are located at the fimbrial tips and at discrete sites along the fimbrial threads. Since fimbriae most frequently act like lectins by binding to the carbohydrate moieties of glycoproteins or glycolipids, fimbrial receptors have frequently been studied with red blood cells of various animal species. Identification and characterization of the binding moieties of ETEC fimbrial adhesins should be useful for the design of new prophylactic or therapeutic strategies. Some studies describing potential receptor or adhesin analogues that interfere with fimbria-mediated colonization have been described in the article.
Bacteriophages have long been recognized to harbor genes that encode various classes of virulence factors, including protein toxins. Some classic examples of phage conversion of grampositive hosts to toxinogenesis are the production of diphtheria toxin (DT) in Corynebacterium diphtheriae and the production of botulinum neurotoxins (BoNTs) in types C and D of Clostridium botulinum. DT has generally been considered mainly responsible for the gross symptoms of diphtheria, and the lack of genetic systems for C. diphtheriae has prevented the identification of other virulence factors associated with its pathogenicity. The association of DT with phages provides a classic example of lysogenic conversion, whereby the bacterial cell acquires traits as a consequence of phage infection. C. botulinum has attracted much interest in recent years, largely due to advances in the study of the structure, function, and genetics of the neurotoxins it encodes and in the therapeutic applications of these toxins for the treatment of several neurologic disorders. BoNTs and tetanus neurotoxin (TeNT) act by selectively blocking the neurotransmission of presynaptic nerve terminals in the peripheral and central nervous systems. The characterization of genes for BoNT and associated proteins of the toxin complexes indicated that these genes are located on the chromosome, on pseudolysogenic bacteriophages, or on plasmids, depending on the serotype. Converting and nonconverting phages from C. botulinum types C and D have been isolated and partially characterized.

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