Virulence factors of Helicobacter pylori

To date a number of virulence factors have been identified and characterised from the gastric pathogen Helicobacter pylori. The vacuolating toxin (VacA) is a major determinant of H. pylori-associated gastric disease. In non-polarised cells, VacA alters the endocytic pathway, resulting in the release of acid hydrolases and the reduction of both extracellular ligand degradation and antigen processing. The toxin forms trans-membrane anion-specific channels and reduces the transepithelial electrical resistance of polarized monolayers. Localization of the VacA channels in acidic intracellular compartments causes osmotic swelling which, together with membrane fusion, leads to vacuole formation. The neutrophil-activating protein of H. pylori (HP-NAP) induces the production of oxygen radicals in human neutrophils via a cascade of intracellular activation events which may contribute to the damage of the stomach mucosa. This protein has recently been shown to be an important antigen in the human immune response to H. pylori infection. In addition, mice vaccinated with recombinant HP-NAP were protected against H. pylori challenge. H. pylori strains that are associated with severe tissue damage and inflammation possess the cag pathogenicity island that contains several genes encoding factors involved in the induction of proinflammatory cytokines/chemokines and of a type IV secretion system involved in the delivery of a highly immunogenic protein, CagA, into eukaryotic cells. Recent advances in our understanding of the involvement of VacA, HP-NAP and the CagA/Type IV secretion system in the H. pylori-associated disease process are discussed in this review.     

Virulence factors of Haemophilus ducreyi

We investigated the susceptibility of virulent and avirulent strains of Haemophilus ducreyi to the bactericidal activity of normal human serum and to phagocytosis and killing by human polymorphonuclear leukocytes (PMNL). Strains were defined as virulent if intradermal inoculation into a rabbit produced a typical necrotic lesion. Nonvirulent strains produced no cutaneous lesions in rabbits. Virulent strains were resistant to the complement-mediated lethal action of normal human and rabbit sera, whereas avirulent strains were susceptible (greater than 95% kill, 60 min). Virulent strains were relatively resistant to phagocytosis and killing by human PMNL, in contrast to the avirulent strains. In past studies polymyxin resistance has been correlated with virulence in H. ducreyi. In our studies, polymyxin resistance could not be correlated with virulence, since polymyxin-sensitive mutants obtained from polymyxin-resistant parent strains remained virulent for rabbits and resistant to bactericidal action of normal serum and phagocytosis and killing by human PMNL. Similarly, polymyxin-resistant mutants obtained from polymyxin-sensitive parent strains remained avirulent for rabbits and susceptible to bactericidal action of normal serum and PMNL. The acquisition of polymyxin resistance was accompanied by the loss of a 47,000-molecular-weight protein. The association of serum resistance and resistance to phagocytosis and killing by human PMNL with virulent strains, as defined by the rabbit intradermal test, suggests that these factors may mediate the pathogenicity of H. ducreyi.     

Virulence factors in uropathogenic E. coli

Escherichia coli isolates from urinary tract infections often exhibit characters different from those isolated from normal faecal samples. Adherence to uroepithelial cells, nature of lipopolysaccharide O antigen and mannose resistant haemagglutination of human erythrocytes are some of the important virulence factors proposed in the pathogenesis of urinary tract infections caused by E. coli. In the present study a total of 100 strains of E. coli isolated from symptomatic cases of urinary tract infections (with significant bacteriuria) were studied for these properties. Faecal isolates of E. coli from adult healthy individuals were also studied as controls. As many as 58 uropathogenic strains showed high affinity for attachment to uroepithelial cells while 28 strains showed adherence at moderate degree. Agglutination of human erythrocytes was induced by as many as 70 uropathogenic strains while in 32 strains haemagglutination was not affected by D-mannose. In control group, adherence was observed in eight strains while 28 strains were haemagglutinating. Of these 28 strains, D-mannose resistant haemagglutination was observed in only one faecal strain. In uropathogenic group O4 was isolated with maximum frequency (12%) followed by O101, O135 and O6.     

Virulence factors in enterococcal infections of orthopedic devices

Enterococci are opportunistic pathogens which today represent one of the leading causes of nosocomial infections. We have examined a collection of 52 Enterococcus faecalis isolated from orthopedic infections to determine if they were characterized by a specific pattern of virulence factors. The isolates were evaluated for biofilm formation, presence of genes coding the enterococcal surface protein (esp) and gelatinase (gelE), as well as for gelatinase production. While the rate of esp-positive isolates was comparable to that found among strains from other clinical sources, we found a significantly higher rate of strong biofilm formers and gelatinase producers. Particularly high was the rate of gelE-carrying strains expressing the gene. Data suggest that these two factors in particular may play an important role in enterococcal infections associated with biomaterials.     

Virulence factors of medically important fungi.

Human fungal pathogens have become an increasingly important medical problem with the explosion in the number of immunocompromised patients as a result of cancer, steroid therapy, chemotherapy, and AIDS. Additionally, the globalization of travel and expansion of humankind into previously undisturbed habitats have led to the reemergence of old fungi and new exposure to previously undescribed fungi. Until recently, relatively little was known about virulence factors for the medically important fungi. With the advent of molecular genetics, rapid progress has now been made in understanding the basis of pathogenicity for organisms such as Aspergillus species and Cryptococcus neoformans. The twin technologies of genetic transformation and "knockout" deletion construction allowed for genetic tests of virulence factors in these organisms. Such knowledge will prove invaluable for the rational design of antifungal therapies. Putative virulence factors and attributes are reviewed for Aspergillus species, C. neoformans, the dimorphic fungal pathogens, and others, with a focus upon a molecular genetic approach. Candida species are excluded from coverage, having been the subject of numerous recent reviews. This growing body of knowledge about fungal pathogens and their virulence factors will significantly aid efforts to treat the serious diseases they cause.     

Virulence factors of clinical Aeromonas caviae isolates

Aeromonas caviae, an ubiquitous aquatic organism, has long been considered to be of low pathogenicity, and its virulence mechanisms are still not clearly understood. Twenty-eight A. caviae isolates of clinical origin, most often monomicrobic, were identified in our university hospital over a four year period. Patients, mostly immunocompromised, were: eight diarrhoeal infants, 13 diarrhoeal adults, seven bacteraemic adults. Adults were frequently suffering from underlying intestinal malignancy, hepatobiliary disease, gastrectomy. Virulence factors were investigated. Adherence, studied by use of tissue culture HEp-2 cells, and staining of characteristic lateral flagella, were observed in diarrhoeal strains. Extracellular hemolytic activity was tested on rabbit erythrocytes suspensions at 25 and 37 degrees C. One blood culture isolate showed an important hemolytic activity at 25 degrees C, but none at 37 degrees C. Treatment with furin activated the aerolysin precursor and resulted in significant hemolysis at 37 degrees C, and fluid accumulation in rabbit ileal loops similar to that of A. hydrophila as control. The presence of the hemolysin gene was confirmed in this strain by PCR. In conclusion, A. caviae was shown to be a pathogen isolated from diarrhoea and bacteraemia in immunocompromised patients with malignancies and low gastric acidity as favouring factors. Virulence including the ability to adhere to cells and the production of lateral flagella was observed in diarrhoeal strains. The expression and the production of extracellular hemolytic activity and enterotoxicity at 37 degrees C depended on the activation of the pore forming toxin aerolysin precursor by furin. In vivo the protoxin is probably processed to its mature form by host proteases.     

Virulence factors of septicemic Escherichia coli strains

Extraintestinal pathogenic Escherichia coli strains (ExPEC) are the cause of a diverse spectrum of invasive human and animal infections, often leading to septicemia. This review deals with the virulence genes of septicemic ExPEC strains. We discuss the meaning of a virulence gene and survey the genomic, genetic and physiological studies on these strains. Apparently, there are a few virulence factors, which are conserved in the septicemic strains, implying that they are essential for the infection. For the other virulence-related genes a high level of diversity is observed, demonstrating that all stages of the infection can be mediated by a number of alternative virulence factors. The variable profile of virulence genes in septicemic E. coli strains, as well as a prevalence of mobility-related sequences point out the existence of a "mix and match" combinatorial system.     

Virulence factors in Escherichia coli urinary tract infection.

Uropathogenic strains of Escherichia coli are characterized by the expression of distinctive bacterial properties, products, or structures referred to as virulence factors because they help the organism overcome host defenses and colonize or invade the urinary tract. Virulence factors of recognized importance in the pathogenesis of urinary tract infection (UTI) include adhesins (P fimbriae, certain other mannose-resistant adhesins, and type 1 fimbriae), the aerobactin system, hemolysin, K capsule, and resistance to serum killing. This review summarizes the virtual explosion of information regarding the epidemiology, biochemistry, mechanisms of action, and genetic basis of these urovirulence factors that has occurred in the past decade and identifies areas in need of further study. Virulence factor expression is more common among certain genetically related groups of E. coli which constitute virulent clones within the larger E. coli population. In general, the more virulence factors a strain expresses, the more severe an infection it is able to cause. Certain virulence factors specifically favor the development of pyelonephritis, others favor cystitis, and others favor asymptomatic bacteriuria. The currently defined virulence factors clearly contribute to the virulence of wild-type strains but are usually insufficient in themselves to transform an avirulent organism into a pathogen, demonstrating that other as-yet-undefined virulence properties await discovery. Virulence factor testing is a useful epidemiological and research tool but as yet has no defined clinical role. Immunological and biochemical anti-virulence factor interventions are effective in animal models of UTI and hold promise for the prevention of UTI in humans.     

Virulence factors and bacteriocins in faecal enterococci of wild boars

The production of antimicrobial, haemolytic and gelatinase activities was tested in 67 enterococci (39 E. faecium, 24 E. hirae, 2 E. faecalis, and 2 Enterococcus spp.), recovered from faecal samples of wild boars. In addition, the presence of genes encoding bacteriocin and virulence factors was also analysed by PCR and sequencing. Production of antimicrobial activity was checked in all enterococci against 9 indicator bacteria and it was detected in 11 E. faecium isolates (16.5%); eight and two of them harboured the genes encoding enterocin A + enterocin B and enterocin L50A/B, respectively. Sixty-seven per cent of our enterococci harboured different combinations of genes of the cyl operon, but none of them contained the complete cyl L(L)L(S)ABM operon, necessary for cytolysin expression. The presence of gel E gene, associated with the fsr ABC locus, was identified in 4 E. faecium and two E. faecalis isolates, exhibiting all of them gelatinase activity. beta -hemolytic activity was not found in our isolates. Both cpd and ace genes, encoding respectively the accessory colonisation factor and pheromone, were detected in two E. faecalis isolates, and the hyl gene, encoding hyalorunidase, in two E. faecium isolates, one of them gelatinase-positive. Genes encoding bacteriocins and virulence factors are widely disseminated among faecal enterococci of wild boars and more studies should be carried out to know the global distribution of these determinants in enterococci of different ecosystems.     

Virulence factors and drug resistance in Escherichia coli isolated from extraintestinal infections

PURPOSE: To determine the virulence factors produced by Escherichia coli isolated from extraintestinal infections, to study the drug resistance pattern in E. coli with special reference to extended spectrum beta -lactamase (ESBL) and to evaluate screening methods for ESBL. METHODS: A total of 152 isolates of E. coli from various extraintestinal infections were screened for virulence factors such as haemolysin, surface hydrophobicity, serum resistance and protease. All the isolates were also studied for antibiotic susceptibility pattern using modified Kirby Bauer disk diffusion method. ESBL production was screened by standard disk diffusion method and confirmed using phenotypic confirmatory method. RESULTS: Among 152 isolates, 36 (23.7%) were haemolytic, 42 (27.6%) were hydrophobic, 132 (86.8%) were serum resistant and only four were positive for protease. Multiple virulence factor were observed in 67 (44%) of isolates. Seventy-nine (51.4%) isolates produced ESBL. ESBL producing isolates showed multidrug resistance. There was a significant association ( P E. coli . CONCLUSIONS: The present study shows the expression of virulence factors and multidrug resistance in E. coli isolated from various extraintestinal infections. The study also shows that appropriate methods of detecting drug resistance and ESBL production are required for the judicious use of antibiotics in managing these infections.     

Virulence factors, pathogenesis and vaccine protection in cholera and ETEC diarrhea

Recent work has provided new insights into the pathogenesis of the potentially life-threatening diarrheas caused by Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC): a new mechanism (post-translational degradation), which is involved in the control of cholera toxin expression, has been discovered. Recent evidence also suggests that vibrios upregulate cholera toxin expression in response to intestinal fluid components, and enterotoxin-carrying bacterial outer membrane vesicles might have a function in ETEC pathogenesis. An important role of the environment is supported by the correlation between cholera incidence and elevated sea surface temperature, which supports the notion that the zooplankton is a V. cholerae reservoir. Additionally, environmental lytic cholera phages could influence cholera seasonality by 'terminating' the seasonal epidemic. Finally, the strong herd immunity elicited by an oral cholera vaccine indicates that cholera vaccination could have a significant public health impact.     

Analysis of factors affecting anaerobic threshold in healthy subjects]

The anaerobic threshold (AT) is used to determine the exercise capacity in patients with heart failure and healthy subjects. To determine the factors affecting AT, we determined the AT in healthy subjects, and examined the factors that determine AT in healthy subjects. One hundred and sixteen healthy subjects (79 men and 37 women) performed on a bicycle a stepwise increasing submaximal exercise. During the work test the parameters usually used in the detection of AT (Vo2, Vco2, VE), blood pressure, heart rate and oxygen saturation were recorded by a computerized system every minute. AT was determined from changes in ventilation and gas-exchange. The fat index was calculated from height and body weight measured at the beginning of the ventilatory function test. A significant correlation was obtained between AT and age, AT and fat index, AT and %VC, AT and maximum heart rate during exercise, AT and recovery rate of heart rate after exercise, and AT and Vo2 at rest. In addition, we examined the relationship among the parameters in 4 groups according to sex and age (30-49; younger, 50-69; older), because sex and age affected most parameters. We found a significant correlation between AT and fat index (older men and women), AT and %VC (younger and older women), AT and Vo2 at rest (younger and older men). We considered that the main factors that determined AT in healthy subjects were age, sex, fat index, %VC and Vo2 at rest.     

Virulence factors in strains of Escherichia coli isolated in urinary tract infections]

In 21 strains of E. coli isolated from patients with cystitis and asymptomatic bacteriuria the authors assessed the group, mannososensitive and mannoresistant agglutination of human, bovine, chick, guinea pig, sheep and pig erythrocytes, the production of haemolysis, colicins, aerobactin, the capacity of strains to induce oedema on mouse paws, the lethal effect in mice, the resistance to tetracycline, streptomycin, chloramphenicol, kanamycin, ampicillin and sulfamethoxidine, the transmission of resistance and sensitivity of strains to the action of fresh human serum. In ten strains the authors recorded also the production of haemolysin and the lethality for mice, in four strains the production of colicin V. production of aerobactin and serum resistance. In three strains the aerobactin production was recorded concurrently with the haemolysin production. In none of the samples P. fimbriae were found.     

Virulence factors in Escherichia coli strains isolated from Swedish piglets with diarrhea.

Parenteral vaccination of sows against Escherichia coli diarrhea in their newborn piglets has become more common during the last decade in Sweden, and the vaccination has generally had positive effects. For more than 20 years we have investigated E. coli strains isolated from piglets and weaned pigs with enteric disorders, noting the presence of O groups, enterotoxins, and adhesins. There has been a continuous change in the frequency of these virulence factors. The present study was performed during 1983 and 1984 to follow this change, since such information is essential for the proper choice of vaccines. A total of 856 E. coli strains were obtained from 683 herds divided into three age groups: 1 to 6 days old, 1 to 6 weeks old, and weaned pigs. O group 149 still dominated in the last two age groups, while O group 101 was, for the first time, the most frequent O group in neonatal piglets. All but four O149 strains carried the K88 antigen, which was found in only one other strain (O group 8). K99 antigen was most often found in O groups 101 and 64, and among all the K99 strains ST mouse was the most common (44 of 57), followed by ST mouse-ST pig strains (12 of 57). The 987P antigen was demonstrated in 26 strains belonging to O groups 141 and OX46 and nontypable strains. Two strains belonging to O group 101 were positive for F41 antigen; one of them also carried the K99 antigen. Among all non-O149 strains, ST mouse was the most common type of enterotoxigenic E. coli ( n = 88), followed in decreasing order by ST mouse-ST pig strains ( n = 69) and ST pig strains ( n = 33). In 114 strains producing enterotoxins no adhesive factor was found. Thus, vaccination of the Swedish sow population for more than 5 years with vaccines containing O149 and K88 antigens has apparently changed the pattern of enterotoxigenic E. coli in neonatal diarrhea. The frequency of O149:K88 strains has been reduced, and O101:K99:ST mouse strains now dominate. However, O149 strains remain the dominant O group in piglets older than 1 week. In spite of all our diagnostic efforts, no virulence factors were detected in about one third of the piglets and weaned pigs with enteric disorders.