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PubMedDate not supplied

Bacterial pathogens in rural water supplies in Southern Alberta, Canada.

Raw river and irrigation water in the Oldman River Basin in southern Alberta was tested for the presence of two bacterial pathogens, Escherichia coli O157:H7 and Salmonella spp., over the last 2 yr (2000-2001). The number of E. coli O157:H7 and Salmonella spp. isolated from raw water peaked during the summer months. While E. coli O157:H7 was only isolated from 11/802 (1.35%) of raw water samples over the entire sampling season in 2000 and from 16/806 (2.05%) of the samples in 2001, the pathogen was isolated one or more times from 10/35 (28.55%) sampling sites in 2000 and from 13/40 (32.55%) sampling sites in 2001. Salmonella was isolated from 44/802 (5.55%) of raw water samples in 2000 and from 122/822 (14.95%) of the samples in 2001; the pathogen was isolated one or more times from 25/35 (71.45%) sampling sites in 2000 and from 29/40 (72.55%) sampling sites in 2001. Certain sites had multiple pathogen isolations in the same year and from year to year. Salmonella Rublislaw was the most common Salmonella serovar isolated in both years, accounting for 52.45% of isolates.

Alberta↗
PubMed2000

Emerging pathogens.

The ever increasing numbers of immunosuppressed individuals has led to a significant increase in the incidence of opportunistic infections, particularly those caused by fungi. The epidemiology of infections caused by the common fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus has been well documented. However, in addition to these, a number of species which have previously been unrecognized (e.g., C. dubliniensis) or have previously been assumed to be non-pathogenic (e.g., Saccharomyces cerevisiae, Scedosporium spp. and Fusarium spp.) have emerged as agents of human disease. Since these species have only been identified recently as human pathogens, their role in disease is poorly understood. In most cases, identification of these species is problematic and therefore their epidemiology has yet to be elucidated adequately. In addition, several of these species fail to respond to conventional antifungal therapies. In this article, we describe the emergence of two separate yeast species (C. dubliniensis and S. cerevisiae) and two separate groups of moulds (Scedosporium prolificans and Fusarium spp.), as human pathogens. It is apparent from what we already know, that much work has yet to be performed before we have a clear understanding of how these species cause disease and most importantly how they can be controlled.

Candida↗
PubMed1959

The streptokinase-plasminogen system. I. Its effect on the pathogenicity of streptococci and other organisms for mice.

Human plasminogen, plasma, or serum increased the pathogenicity of six streptokinase-positive streptococcal strains for mice. Combinations of commercial streptokinase and plasminogen or streptokinase and plasma did not usually increase mouse mortality to a greater degree than did plasminogen or plasma alone, suggesting that the maximal effective amount of streptokinase was produced by the organisms. The pathogenicity of Salmonella paratyphi (fibrinolysin variable) and a Group D streptococcus (streptokinase-negative) was not increased by plasminogen, plasma, or streptokinase, whereas a combination of streptokinase and plasminogen, or streptokinase and plasma did significantly increase mouse mortality resulting from these organisms. Combinations of certain concentrations of streptokinase and plasminogen increased the pathogenicity of a fibrinolysin-negative staphylococcal strain for mice to a greater extent than did either substance alone. The observed results provide evidence that streptokinase, by an interaction with plasminogen, contributes to the pathogenicity of streptokinase-positive streptococci.

Animals↗
PubMed1999

High pathogenic potential of low-affinity autoantibodies in experimental autoimmune hemolytic anemia.

To assess the potency of low-affinity anti-red blood cell (RBC) autoantibodies in the induction of anemia, we generated an immunoglobulin (Ig)G2a class-switch variant of a 4C8 IgM anti-mouse RBC autoantibody, and compared its pathogenic potential with that of its IgM isotype and a high-affinity 34-3C IgG2a autoantibody. The RBC-binding activity of the 4C8 IgG2a variant was barely detectable, at least 1,000 times lower than that of its IgM isotype, having a high-binding avidity, and that of the 34-3C IgG2a monoclonal antibody (mAb). This low-affinity feature of the 4C8 mAb was consistent with the lack of detection of opsonized RBCs in the circulating blood from the 4C8 IgG2a-injected mice. However, the 4C8 IgG2a variant was highly pathogenic, as potent as its IgM isotype and the 34-3C IgG2a mAb, due to its capacity to interact with Fc receptors involved in erythrophagocytosis. In addition, our results indicated that the pentameric form of the low-affinity IgM isotype, by promoting the binding and agglutination of RBCs, is critical for its pathogenic activity. Demonstration of the remarkably high pathogenic potency of low-affinity autoantibodies, if combined with appropriate heavy chain effector functions, highlights the critical role of the Ig heavy chain constant regions, but the relatively minor role of autoantigen-binding affinities, in autoimmune hemolytic anemia.

Anemia, Hemolytic, Autoimmune↗
PubMed2002

Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis.

Antigen-specific T helper type 1 (Th1) cells mediate protective immunity against a range of infectious diseases, including that caused by Bordetella pertussis. Distinct T cell subtypes that secrete interleukin (IL)-10 or tumor growth factor (TGF)-beta are considered to play a role in the maintenance of self-tolerance. However, the antigens recognized by these regulatory T cells in vivo have not been defined. Here we provide the first demonstration of pathogen-specific T regulatory type 1 (Tr1) cells at the clonal level and demonstrate that these cells are induced at a mucosal surface during an infection where local Th1 responses are suppressed. Tr1 clones specific for filamentous hemagglutinin (FHA) and pertactin were generated from the lungs of mice during acute infection with B. pertussis. The Tr1 clones expressed T1/ST2 and CC chemokine receptor 5, secreted high levels of IL-10, but not IL-4 or interferon (IFN)-gamma, and suppressed Th1 responses against B. pertussis or an unrelated pathogen. Furthermore, FHA inhibited IL-12 and stimulated IL-10 production by dendritic cells (DCs), and these DCs directed naive T cells into the regulatory subtype. The induction of Tr1 cells after interaction of a pathogen-derived molecule with cells of the innate immune system represents a novel strategy exploited by an infectious pathogen to subvert protective immune responses in vivo.

Adhesins, Bacterial↗
PubMed2003

Vaccine immunity to pathogenic fungi overcomes the requirement for CD4 help in exogenous antigen presentation to CD8+ T cells: implications for vaccine development in immune-deficient hosts.

Systemic fungal infections with primary and opportunistic pathogens have become increasingly common and represent a growing health menace in patients with AIDS and other immune deficiencies. T lymphocyte immunity, in particular the CD4+ Th 1 cells, is considered the main defense against these pathogens, and their absence is associated with increased susceptibility. It would seem illogical then to propose vaccinating these vulnerable patients against fungal infections. We report here that CD4+ T cells are dispensable for vaccine-induced resistance against experimental fungal pulmonary infections with two agents, Blastomyces dermatitidis an extracellular pathogen, and Histoplasma capsulatum a facultative intracellular pathogen. In the absence of T helper cells, exogenous fungal antigens activated memory CD8+ cells in a major histocompatibility complex class I-restricted manner and CD8+ T cell-derived cytokines tumor necrosis factor alpha, interferon gamma, and granulocyte/macrophage colony-stimulating factor-mediated durable vaccine immunity. CD8+ T cells could also rely on alternate mechanisms for robust vaccine immunity, in the absence of some of these factors. Our results demonstrate an unexpected plasticity of immunity in compromised hosts at both the cellular and molecular level and point to the feasibility of developing vaccines against invasive fungal infections in patients with severe immune deficiencies, including those with few or no CD4+ T cells.

Animals↗
PubMed2004

Pathogenic profiles and molecular signatures of antinuclear autoantibodies rescued from NZM2410 lupus mice.

Two outstanding questions concerning antinuclear antibodies (ANAs) in lupus involve their pathogenic potential and their molecular signatures. To address these questions, a panel of 56 antinuclear and 47 nonnuclear binding monoclonal antibodies was rescued from four seropositive NZM2410 lupus mice. The monoclonals varied in their reactivity to nucleosomes, ssDNA, dsDNA, and glomerular substrate. A large fraction of the antibodies demonstrated apparent polyreactivity (to DNA, histones, and glomerular antigens) due to bound, DNase-1 sensitive nuclear antigenic bridges. Although nephrophilic immunoglobulin (Ig) M and IgG antibodies were the most pathogenic, the dsDNA-binding antibodies were modestly so; in contrast, antinucleosome antibodies were clearly not pathogenic. Compared with the nonnuclear antigen-binding monoclonal antibodies rescued from the same mice, ANAs exhibited increased utilization of VH5/7183 genes and highly cationic heavy chain (HC) CDR3 regions. Most intriguingly, the CDR3 regions of the ANAs exhibited alternating arginine/lysine peaks at H96, H98, and H100, with neutral troughs at H95, H97, and H99. To summarize, glomerular-binding anti-dsDNA antibodies appear to be the most pathogenic variety of lupus autoantibodies. The presence of an alternating charge pattern in their HC CDR3 regions appears to be a prominent hallmark of ANAs.

Amino Acid Sequence↗
PubMed1993

Menstruation as a defense against pathogens transported by sperm.

Sperm are vectors of disease. During mammalian insemination bacteria from the male and female genitalia regularly cling to sperm tails and are transported to the uterus. I propose that menstruation functions to protect the uterus and oviducts from colonization by pathogens. Menstrual blood exerts mechanical pressure on uterine tissue, forcing it to shed, and delivers large numbers of immune cells throughout the uterine cavity, directly combating pathogens. The mechanisms of menstruation show evidence of adaptive design. Spiral arteries that open to the lining of the uterus trigger menstruation by abruptly constricting, which deprives the local tissue of blood, and then abruptly dilating, which causes blood to force loose the necrotic tissue. Menstrual blood flows easily, unlike blood at most wound sites, because it lacks the normal level of clotting factors. Overt (externally visible) or covert (not externally visible) menstruation has been documented in many species of primate, including Old World monkeys and apes, New World monkeys, and prosimians, as well as in various species of bat and insectivore. The antipathogen hypothesis predicts that: (1) menstruation (overt or covert) is either universal or nearly so among mammalian species; (2) if the latter, then the existence of menstruation among species varies inversely with the probability of becoming pregnant per estrous cycle (menstruation would be especially adaptive in species with significantly less than 100% probability of becoming pregnant per estrous cycle); (3) among menstruating species, the average degree of menstrual bleeding for a given species is a function of the factors affecting menstruation's costs and benefits--in particular, the degree of bleeding is positively correlated with the average body size and sexually transmitted pathogen load of that species (profuse bleeding would be especially adaptive in large-bodied species with either promiscuous breeding systems or continuous sexual receptivity); and (4) other forms of normal uterine bleeding--proestrous, periovulatory, implantation, and postpartum--also have an antipathogen function. The hypothesis presented in this article has implications for the diagnosis, treatment and prevention of uterine infection and, therefore, for the prevention of pathogen-induced infertility. The uterus appears to be designed to increase its bleeding if it detects infection: Human uteri that become infected (or otherwise inflamed) bleed more profusely, bleed on more days per cycle, and often bleed intermittently throughout the cycle. Thus artificially curtailing infection-induced uterine bleeding may be contraindicated.

Animals↗
PubMed2004

Pathogen-specific early mortality in very low birth weight infants with late-onset sepsis: a national survey.

BACKGROUND: Late-onset sepsis (LOS) is an important cause of mortality among very low birth weight (VLBW) infants, and deaths occurring within 3 days after the onset of sepsis can probably be ascribed to sepsis. We examined the association of sepsis due to specific pathogens with the risk for early mortality after the onset of LOS, adjusted for perinatal and neonatal risk factors. METHODS: From 1995 through 2001, information about 10,215 infants was gathered and deposited in the Israel National VLBW Infant Database. The study population was composed of 2644 infants, of which each had >or=1 events of LOS (totalling 3462 events). Logistic regression models were used to calculate the crude and adjusted risk for early mortality. RESULTS: Early mortality was associated with 179 LOS events (5.2% of 3,462); the range of pathogens associated with these events included coagulase-negative staphylococci (CoNS), which were the cause of 1.8% of LOS events associated with early mortality, and Pseudomonas species, which were the cause of 22.6% of such events. Early mortality after LOS, adjusted for neonatal risk factors, was significantly associated with sepsis due to certain pathogens: Pseudomonas species (odds ratio [OR], 12.3); Klebsiella species (OR, 6.3); Serratia species (OR, 6.2); Escherichia species (OR, 4.3); Enterobacter species (OR, 4.1); and Candida species (OR, 3.2), compared with sepsis due to CoNS . In addition, lower gestational age, lower chronological age, small size for gestational age, and grade 3-4 intraventricular hemorrhage, each had an independent association with early mortality. CONCLUSIONS: Klebsiella sepsis and Pseudomonas sepsis were associated with a 6.3-fold and 12.3-fold increased risk of early mortality, respectively, and accounted for 41.9% of all early deaths associated with LOS. Considering the aggressive nature of sepsis caused by these pathogens, empiric antibiotic therapy active against these organisms is worth consideration for VLBW infants with presumed LOS.

Age of Onset↗
PubMed2000

Antimicrobial activity of home disinfectants and natural products against potential human pathogens.

OBJECTIVE: To assess the efficacy of both natural products (vinegar, baking soda) and common commercial disinfectants (Vesphene IIse, TBQ, Clorox, Lysol Disinfectant Spray, Lysol Antibacterial Kitchen Cleaner, Mr. Clean Ultra, ethanol) designed for home or institutional use against potential human pathogens, including selected antibiotic-resistant bacteria. DESIGN: A quantitative suspension test was used to assess the efficacy of selected disinfectants following exposure times of 30 seconds and 5 minutes. Activity was assessed against Staphylococcus aureus, Salmonella choleraesuis, Escherichia coli O157:H7, and Pseudomonas aeruginosa. Selected disinfectants were also tested against poliovirus, vancomycin-susceptible and -resistant Enterococcus species, and methicillin-susceptible and -resistant S. aureus. RESULTS: The following compounds demonstrated excellent antimicrobial activity (>5.6-8.2 log10 reduction) at both exposure times: TBQ, Vesphene, Clorox, ethanol, and Lysol Antibacterial Kitchen Cleaner. Mr. Clean eliminated 4 to >6 logs10 and Lysol Disinfectant approximately 4 logs10 of pathogenic microorganisms at both exposure times. Vinegar eliminated <3 logs10 of S. aureus and E. coli, and baking soda <3 logs10 of all test pathogens. All tested chemical disinfectants completely inactivated both antibiotic-resistant and -susceptible bacteria at both exposure times. Only two disinfectants, Clorox and Lysol, demonstrated excellent activity (>3 log10 reduction) against poliovirus. CONCLUSIONS: A variety of commercial household disinfectants were highly effective against potential bacterial pathogens. The natural products were less effective than commercial household disinfectants. Only Clorox and Lysol disinfectant were effective against poliovirus.

Disinfectants↗
PubMed2006

Pathogen relatedness affects the prevalence of within-host competition.

Although the evolutionary consequences of within-host competition among pathogens have been examined extensively, there exists a critical gap in our understanding of factors determining the prevalence of multiple infections. Here we examine the effects of relatedness among strains of the anther-smut pathogen Microbotryum violaceum on the probability of multiple infection in its host, Silene latifolia, after sequential inoculations. We found a significantly higher probability of multiple infection when interacting strains were more closely related, suggesting mechanisms of competitive exclusion that are conditional on genotypic characteristics of the strains involved. Pathogen relatedness therefore determines the prevalence of multiple infection in addition to its outcome, with important consequences for our understanding of virulence evolution and pathogen population structure and diversity.

Basidiomycota↗
PubMed2006

A gravity model for the spread of a pollinator-borne plant pathogen.

Many pathogens of plants are transmitted by arthropod vectors whose movement between individual hosts is influenced by foraging behavior. Insect foraging has been shown to depend on both the quality of hosts and the distances between hosts. Given the spatial distribution of host plants and individual variation in quality, vector foraging patterns may therefore produce predictable variation in exposure to pathogens. We develop a "gravity" model to describe the spatial spread of a vector-borne plant pathogen from underlying models of insect foraging in response to host quality using the pollinator-borne smut fungus Microbotryum violaceum as a case study. We fit the model to spatially explicit time series of M. violaceum transmission in replicate experimental plots of the white campion Silene latifolia. The gravity model provides a better fit than a mean field model or a model with only distance-dependent transmission. The results highlight the importance of active vector foraging in generating spatial patterns of disease incidence and for pathogen-mediated selection for floral traits.

Animals↗
PubMed1998

Staphylococcus aureus: a well-armed pathogen.

Staphylococcus aureus is a virulent pathogen that is currently the most common cause of infections in hospitalized patients. S. aureus infection can involve any organ system. The success of S. aureus as a pathogen and its ability to cause such a wide range of infections are the result of its extensive virulence factors. The increase in the resistance of this virulent pathogen to antibacterial agents, coupled with its increasing prevalence as a nosocomial pathogen, is of major concern. The core resistance phenotype that seems to be most associated with the persistence of S. aureus in the hospital is methicillin resistance. Methicillin resistance in nosocomial S. aureus isolates has been increasing dramatically in United States hospitals and is also associated with resistance to other useful antistaphylococcal compounds. Possible ways to decrease the incidence of nosocomial S. aureus infections include instituting more effective infection control, decreasing nasal colonization, developing vaccines, and developing new or improved antimicrobials.

Cross Infection↗
PubMed2005

Multiple sample flow through immunomagnetic separator for concentrating pathogenic bacteria.

The standard method of immunomagnetic separation for isolating pathogenic bacteria from food and environmental matrices processes 1 ml volumes. Pathogens present at low levels (<0.5 pathogenic bacteria/g) will not be consistently detected by this method. Here a multiple sample flow through immunomagnetic separator has been designed and tested to process large volume samples (50 to 250 ml). Preliminary results show >97% recovery of polydisperse magnetic particles (diameter range 1 to 8 microm) containing 29-33% w/w Fe3O4 content. Between 70 and 130 times more of the pathogenic bacteria Escherichia coli O157 is recovered from PBS compared with the standard 1 ml method. Also, the recovery of E. coli O157 from beef mince homogenates, after a 4 h incubation at 42 degrees C, is between 80 and 180 times higher than the standard 1 ml method.

Bacteria↗
PubMed2004

Envelope glycoprotein determinants of increased entry in a pathogenic simian-human immunodeficiency virus (SHIV-HXBc2P 3.2) passaged in monkeys.

Passage of a nonpathogenic simian-human immunodeficiency virus (SHIV-HXBc2) in monkeys resulted in changes in the viral envelope glycoproteins that are responsible for a dramatic increase in replication and pathogenicity in vivo. Here, we show that the envelope glycoproteins of the pathogenic SHIV-HXBc2P 3.2 mediate virus entry into rhesus monkey peripheral blood mononuclear cells (PBMC) more efficiently than the parental SHIV-HXBc2 envelope glycoproteins, and study the basis for this increase. Both parental and pathogenic SHIVs exclusively use CXCR4 as a coreceptor. The determinants of the increased entry associated with the SHIV-HXBc2P 3.2 envelope glycoproteins are located in both the gp120 and gp41 subunits. Changes in the gp120 V3 variable loop specify a decreased sensitivity to SDF-1, consistent with an increase in the affinity of the HXBc2P 3.2 gp120 glycoprotein for CXCR4. Thus, multiple changes in the gp120 variable loops and the gp41 ectodomain of a pathogenic SHIV cooperate to allow enhanced replicative capacity, which in part results from increased chemokine receptor binding.

Animals↗
PubMed2006

Pathogens and host DNA in Ixodes ricinus nymphal ticks from a German forest.

Unfed nymphs of Ixodes ricinus were collected from vegetation in a forest on the outskirts of Berlin, Germany and were analyzed for host and pathogen DNA. Pathogens were detected in 47% of the ticks. Borrelia afzelii was the commonest pathogen detected, followed by Rickettsia helvetica. Other pathogens included B. valaisiana, B. garinii, B. burgdorferi sensu stricto, Anaplasma phagocytophilum, and a relapsing fever-like Borrelia. Most of the host DNA detected was of rodent origin and was associated with infection by B. afzelii, R. helvetica, and A. phagocytophilum. Bird DNA was associated with B. valaisiana and B. garinii, and ruminant DNA with A. phagocytophilum. B. afzelii was also found in two ticks that contained bird DNA.

Anaplasma phagocytophilum↗
PubMed2006

Rapid accumulation of trihydroxy oxylipins and resistance to the bean rust pathogen Uromyces fabae following wounding in Vicia faba.

BACKGROUND AND AIMS: Insect damage to plants leads to wound-activated responses directed to healing of damaged tissues, as well as activation of defences to prevent further insect damage. Negative cross-talk exists between the jasmonic acid-based signalling system that is activated upon insect attack and the salicylic acid-based system frequently activated following pathogen infection. Thus, insect attack may compromise the ability of the plant to defend itself against pathogens and vice versa. However, insect herbivory and mechanical wounding have been shown to reduce fungal infections on some plants, although the underlying mechanisms remain to be defined. This work examines the effects of mechanical wounding on rust infection both locally and systemically in the broad bean, Vicia faba and follows changes in oxylipins in wounded leaves and unwounded leaves on wounded plants. METHODS: The lamina of first leaves was wounded by crushing with forceps, and first and second leaves were then inoculated, separately, with the rust Uromyces fabae at various times over a 24 h period. Wounded first leaves and unwounded second leaves were harvested at intervals over a 24 h period and used for analysis of oxylipin profiles. KEY RESULTS Mechanical wounding of first leaves of broad bean led to significantly reduced rust infection in the wounded first leaf as well as the unwounded second leaf. Increased resistance to infection was induced in plants inoculated with rust just 1 h after wounding and was accompanied by rapid and significant accumulation of jasmonic acid and two trihydroxy oxylipins in both wounded first leaves and unwounded second leaves. The two trihydroxy oxylipins were found to possess antifungal properties, reducing germination of rust spores. CONCLUSIONS: These results demonstrate the rapidity with which resistance to pathogen infection can be induced following wounding and provides a possible mechanism by which pathogen infection might be halted.

Animals↗
PubMed2026

Whole-genome prediction of bacterial pathogenic capacity on novel bacteria using protein language models with PathogenFinder2.

MOTIVATION: Infectious diseases continue to be a leading cause of mortality and pose a significant global health threat. Thus, the development of tools for surveillance and early detection of emerging pathogens is needed. RESULTS: We introduce PathogenFinder2, a novel, alignment-free, taxonomy-agnostic model for predicting bacterial pathogenic capacity in humans using protein language models. It outperforms previous methods, particularly for novel taxa, and provides interpretable outputs by highlighting proteins most relevant to pathogenic potential. These insights aid the identification of virulence factors, vaccine targets, and infection-related metabolic pathways. Furthermore, we introduce the Bacterial Pathogenic Capacity Landscape, which reveals patterns linked to host condition, infection site, microbial antagonism, and environmental origin. AVAILABILITY: The model is freely available online at https://genepi.dk/pathogenfinder2, or as a standalone program (https://github.com/genomicepidemiology/PathogenFinder2).

Genome, Bacterial↗