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Physiological and pathogenic characteristics of Nocardia brasiliensis isolated from human mycetomas.

A previous analysis of the physiological properties of Nocardia brasiliensis strains isolated from soil of Tucumán proves that non-pathogenic strains have a different behaviour pattern from the pathogenic strains. In the present paper, 16 Nocardia brasiliensis strains isolated from human mycetomas were studied in the same way. The object is to determine if any of the Nocardia brasiliensis present in soil can produce human mycetomas. The macro and micromorphological, biochemical (17 tests), physiological (4 tests) and pathological characteristics were determined for each of the strains. Experimental pathogenicity was determined using albino Swiss mice by inoculation into the footpads. The strains of Nocardia brasiliensis that cause human mycetomas have the same physiological pattern and experimental pathogenicity as the virulent strains present in soil.

Animals↗

Aggravation of pathogenicity of an avian influenza virus by adaptation to quails.

Influenza virus A/turkey/Ontario/7732/66 (H 5 N 9), which is highly pathogenic to chickens, is nonpathogenic to quails. After intratracheal or intramuscular inoculation of quails, virus replication was limited to the respiratory tract, genital organs, and pancreas. However, aggravation of the pathogenicity was achieved through adaptation only by several passages of lung homogenates in quails. The adapted virus caused a fatal generalized infection in quails as well as in chickens. The pathogenic change of the virus could not be explained by a change in the proteolytic cleavability of the hemagglutinin, because no difference was found in the cleavability between the original and the adapted viruses. The adapted virus formed larger plaques and grew a little faster than the original one in both chicken embryo and quail embryo cells. The faster multiplication of the adapted virus at the site of infection might be the reason for its change in pathogenicity. The original virus could circulate among quails by a direct contact transmission without causing disease. The shed virus, however, caused a fatal infection in chickens when they were kept in contact with the infected quails. The epidemiological significance of this observation is discussed.

Adaptation, Physiological↗

[Definition of the term "work with pathogenic microorganism" a problem of quality control in the food industry (author's transl)].

According to the Federal Communicable Disease Act a permission is required for work with pathogenic microorganisms. Current interpretations of these legal requirements, however, pose considerable problems. For example it is quite open whether the determination of total counts or sterility tests are to be considered as work with pathogenic organisms or not. In a recent article a prominent representative of the federal health authority has discussed some of the aspects of this topic Unfortunately no progress in defining the term "work with pathogenic microorganisms" has been achieved. Therefore it seemed necessary to come back to that issue. The discussion presented here shows that the wording of the Federal Communicable Disease Act implies a rather restrictive interpretation of these provisions. Total counts, sterility tests, microbial flora analysis and salmonella tests in food quality control should not be considered as work with pathogenic microorganisms at all. Because of the great importance of these legal provisions health authorities definitely should avoid vague interpretation. Instead, if necessary, proper amendment of the legislation should be considered.

Bacteria↗

Pathogen evolution within host individuals as a primary cause of senescence.

This paper discusses a novel theory of senescence: the community of pathogens within each host individual evolves during the life-time of the host, and in doing so progressively reduces host vigour. I marshal evidence that asymptomatic host individuals maintain persistent populations of viral pathogens; that these pathogens replicate; that they are often extremely variable; that selection within hosts causes the evolution of pathogens better able to exploit the host; that selection is host-specific; and that such evolving infections cause appreciable and progressive deterioration. Experimental approaches to testing the theory are discussed.

Aging↗

[Changes in the antibiotic sensitivity of urinary tract pathogens (author's transl)].

The resistance of 2,314 bacterial strains from 1968 to 1972 was investigated drawing on case histories from the Munich University Urological Clinic. Using the disc-diffusion method 12,160 sensitivity tests were conducted with these strains against gentamicin, co-trimoxazole, ampicillin, tetracycline and chloramphenicol. The material was compiled from 35,000 individual data by means of modern electronic data processing and evaluated according to variable criteria. As expected the incidence of resistance in hospital-acquired pathogens was considerably higher than that in community-acquired pathogens; however, the resistance pattern of hosptial-acquired pathogens remained essentially unchanged from 1968 to 1972, whereas a significant increase of resistance in community-acquired infections was recorded. It can thus be concluded that the methods used in this clinic for combatting hospital infection and a more critical attitude towards anti-bacterial therapy have had positive results. An express warning is issued against unspecific antibacterial therapy which is often administered outside the clinic on the pretext of long-term therapy. In the light of the resistance situation of urinary tract pathogens, antibiotics should be used sparingly, keeping in mind the acidification of urine and the wash-out principle by means of high fluid intake.

Ampicillin↗

Pathogenicity of entamoeba histolytica.

The pathogenicity of Entamoeba histolytica is discussed from an immunologic point of view. The evidence that there is some "trigger" mechanism which converts a commensal dwelling organism into a tissue invasive pathogen is rejected as inadequate. The number of liver abscess cases in comparison with the number of intestinal amebic infections in a population is so low that this in itself suggests that tissue invasion is a rare event in the life history of the ameba. A review is made of the experimental evidence that some type of sensitization is necessary before ameba can invade tissue. In postulating an immunologic basis for the pathogenicity of ameba, a parallel between the behavior of malignant cells in the body and an amebic infection in the gut is made. An appealing hypothesis which deserves further research effort is that an altered immune response is the basis for the pathogenic mechanism in the host.

Antibody Formation↗

Colonization pattern of the digestive tract by potentially pathogenic microorganisms: colonization-controlling mechanisms and consequences for antibiotic treatment.

An outline is given of the various host-related and flora-related parts of the colonization resistance of the digestive tract. The host-related part of the colonization resistance has been found to be somewhat decreased by sublethal irradiation and leukemia (or chemotherapy), while treatment with antibiotics active against gram-positive flora may severely decrease the colonization resistance (depending on the antibiotic concentration established within the digestive tract during antibiotic therapy). The flora-related part of the colonization resistance, which controls colonization by potentially pathogenic microorganisms, differs greatly from one individual to the next. This observation appears to be important for the host-related part of the colonization resistance. Finally, it is concluded that in the clinical situation preference should be given to antibiotics which do not affect the part of the flora constituting colonization resistance for two reasons: 1) to limit the spread of (multi-) resistant potentially pathogenic microorganisms and 2) for infection prophylaxis in immunocompromised patients. In the latter situation, the potentially pathogenic microorganisms in the flora are selectively eliminated from the digestive tract, provided the antimicrobial drugs used for selective decontamination are active against the endogenous potentially pathogenic microorganisms and given in sufficient (oral) doses.

Animals↗

Antimicrobial activities of Streptomyces pulcher, S. canescens and S. citreofluorescens against fungal and bacterial pathogens of tomato in vitro.

Thirty-seven actinomycete species isolated from fertile cultivated soils in Egypt were screened for the production of antimicrobial compounds against a variety of test organisms. Most of the isolates exhibited antimicrobial activities against Gram-positive, Gram-negative, and acid-fast bacteria, yeasts and filamentous fungi, with special attention to fungal and bacterial pathogens of tomato. On starch-nitrate agar, 14 strains were active against Fusarium oxysporum f.sp. lycopersici (the cause of Fusarium wilt), 18 against Verticillium albo-atrum (the cause of Verticillium wilt), and 18 against Alternaria solani (the cause of early blight). In liquid media, 14 isolates antagonized Pseudomonas solanacearum (the cause of bacterial wilt) and 20 antagonized Clavibacter michiganensis ssp. michiganensis (the cause of bacterial canker). The most active antagonists of the pathogenic microorganisms studied were found to be Streptomyces pulcher, S. canescens (syn. S. albidoflavus) and S. citreofluorescens (syn. S. anulatus). The antagonistic activities of S. pulcher and S. canescens against pathogenic fungi were assessed on solid media, and those of S. pulcher and S. citreofluorescens against pathogenic bacteria in liquid media under shaking conditions. The optimum culture conditions were determined.

Anti-Bacterial Agents↗

Pathogenic Neisseria--interplay between pro- and eukaryotic worlds.

The pathogenic Neisseria species constitute a multi-faceted infection model of a highly adapted pathogen-host relationship. Several bacterial and host-cell factors involved in the cellular cross-talk have been recently unraveled. Using Neisseria gonorrhoeae as a prototype, several structurally variable surface proteins, including pili and Opa proteins, have been revealed as adhesins recognizing distinct host-cell receptors. The Opa proteins, in particular, are important in facilitating interaction with heparan sulfate proteoglycan receptors and members of the CD66 and integrin receptor families. These interactions not only enable the pathogens' anchoring, and penetration into, the human mucosa but also stimulate cellular signaling cascades involving the phosphatidylcholine-dependent phospholipase C, acidic sphingomyelinase and protein kinase C in epithelial cells, and Src-related kinases, Rac1, p21-activated kinase and Jun N-terminal kinase in phagocytic cells. Activation of these pathways is essential for the entry and intracellular accommodation of the pathogens but also leads to an early induction of cytokine release, thus priming the immune response. It is believed that detailed knowledge of cellular signaling cascades activated by infection will aid us in applying known and novel interfering drugs, in addition to classical antibiotic therapy, to the therapeutic and prophylactic treatment of persistent or otherwise difficult-to-treat bacterial infections.

Epithelial Cells↗

Transformation: a tool for studying fungal pathogens of plants.

Plant diseases caused by plant pathogenic fungi continuously threaten the sustainability of global crop production. An effective way to study the disease-causing mechanisms of these organisms is to disrupt their genes, in both a targeted and random manner, so as to isolate mutants exhibiting altered virulence. Although a number of techniques have been employed for such an analysis, those based on transformation are by far the most commonly used. In filamentous fungi, the introduction of DNA by transformation typically results in either the heterologous (illegitimate) integration or the homologous integration of the transforming DNA into the target genome. Homologous integration permits a targeted gene disruption by replacing the wild-type allele on the genome with a mutant allele on transforming DNA. This process has been widely used to determine the role of newly isolated fungal genes in pathogenicity. The heterologous integration of transforming DNA causes a random process of gene disruption (insertional mutagenesis) and has led to the isolation of many fungal mutants defective in pathogenicity. A big advantage of insertional mutagenesis over the more traditional chemical or radiation mutagenesis procedures is that the mutated gene is tagged by transforming DNA and can subsequently be cloned using the transforming DNA. The application of various transformation-based techniques for fungal gene manipulation and how they have increased our understanding and appreciation of some of the most serious plant pathogenic fungi are discussed.

Agrobacterium tumefaciens↗

Pathogen, host and environmental factors contributing to the pathogenesis of listeriosis.

Listeriosis is a severe human and animal disease caused by two species of pathogenic bacteria from the genus Listeria, L. monocytogenes and L. ivanovii. In humans, listeriosis is overwhelmingly a foodborne disease, yet much remains to be learned regarding the transmission dynamics of pathogenic Listeria from the environment, through food, to humans. Similarly, our understanding of the various host, pathogen and environmental factors that impact the pathogenesis of listeriosis at the cellular and molecular level is incomplete. This review will summarize what is currently known about animal and human listeriosis, detail the pathogen, host and environmental factors that contribute to pathogenesis and, finally, examine the interactions among those factors that influence the occurrence of human infection.

Animals↗

[Detection of periodontal pathogenic microorganisms in atheromatous plaque. Preliminary results].

INTRODUCTION: Recent studies suggest that chronic infections, including those associated with periodontitis, increase the risk for coronary vascular disease. We hypothesize that oral microorganisms including periodontal bacterial pathogens enter the blood stream during transient bacteremias where they may play a role in the development and progression of atherosclerosis. MATERIALS AND METHODS: To test this hypothesis, 34 human specimens obtained during carotid endarterectomy or bypass procedures were examined by use of specific oligonucleotide primers for Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans and Bacteroides forsythus in polymerase chain reaction (PCR) assays. RESULTS: Twenty (59%) of the 34 specimens tested positive for bacterial 16S rDNA. Subsequent hybridization of the bacterial 16S rDNA positive specimens with species-specific oligonucleotide probes revealed that 32.4% of the 34 atheromas tested positive for at least one of the target periodontal pathogens. Further analysis of the results in the bacterial positive group (n = 20) shows that 55% of the atheromas tested positive for at least one of the target periodontal pathogens. CONCLUSION: These findings indicate that periodontal pathogens are present in atherosclerotic plaques, where they may play a role in the development and progression of atherosclerosis leading to coronary vascular disease and other clinical sequelae.

Adult↗

Autophagy in innate and adaptive immunity against intracellular pathogens.

Autophagy delivers cytoplasmic constituents for lysosomal degradation. Recent studies have demonstrated that this pathway mediates resistance to pathogens and is targeted for immune evasion by viruses and bacteria. Lysosomal degradation products, including pathogenic determinants, are then surveyed by the adaptive immune system to elicit antigen-specific T cell responses. CD4(+) T helper cells have been shown to recognize nuclear and cytosolic antigens via presentation by major histocompatibility complex (MHC) class II molecules after autophagy. Furthermore, some sources of natural MHC class II ligands display characteristics of autophagy substrates, and autophagosomes fuse with late endosomes, in which MHC class II loading is thought to occur. Although MHC class II antigen processing via autophagy has so far mainly been described for professional antigen-presenting cells like B cells, macrophages, and dendritic cells, it might be even more important for cells with less endocytic potential, like epithelial cells, when these express MHC class II at sites of inflammation. Therefore, autophagy might contribute to immune surveillance of intracellular pathogens via MHC class II presentation of intracellular pathogen-derived peptides.

Adaptation, Physiological↗

[Spectrum of pathogens and resistance to antibiotics in urinary tract infections and the consequences for antibiotic treatment: study of urology inpatients with urinary tract infections (1994-2001)].

From 1994 to 2001 all uropathogens of urology inpatients were identified and the sensitivity to 14 antibiotics was tested [trimethoprim (TMP)/sulfamethoxazole (SMZ), ciprofloxacin, ampicillin, mezlocillin, ampicillin/sulbactam, piperacillin/tazobactam, cefuroxime, cefpodoxime, cefotaxime, ceftazidime, gentamicin, penicillin, oxacillin, and vancomycin]. The following results were obtained: 1. No general trend toward an increase in resistance was noted during the observation period except for E. coli resistance to TMP/SMZ (25.1% in 2000) and ciprofloxacin (10.4% in 2000). 2. Vancomycin-intermediary staphylococci or vancomycin-resistant enterococci played no role. 3. The lowest resistance to all pathogens was found for piperacillin/tazobactam (8.4% in 2001); carbapenems were not tested. 4. If uropathogens are stratified into gram-positive and gram-negative bacteria, for oral administration, ciprofloxacin is the antibiotic with the lowest resistance rate for urinary tract infections with gram-negative pathogens and ampicillin/sulbactam for gram-positive pathogens. 5. Subsequent to further differentiation of the pathogens with simple tests that can be performed after overnight incubation of the culture, empirical antibiotic therapy can then be effectively employed. To draw the correct conclusions from these data, the urologist must either be personally involved in the analytical procedure or receive the interim results promptly.

Anti-Bacterial Agents↗

The Rxo1/ Rba1 locus of maize controls resistance reactions to pathogenic and non-host bacteria.

Infiltration of different maize lines with a variety of bacterial pathogens of maize, rice and sorghum identified qualitative differences in resistant reactions. Isolates from two bacterial species induced rapid hypersensitive reactions (HR) in some maize lines, but not others. All isolates of the non-host pathogen Xanthomonas oryzae pv. oryzicola (bacterial leaf streak disease of rice) and some isolates of the pathogenic bacterium Burkholderia andropogonis induced HR when infiltrated into maize line B73, but not Mo17. Genetic control of the HR to both bacteria segregated as a single dominant gene. Surprisingly, both phenotypes mapped to the same locus, indicating they are either tightly linked or controlled by the same gene. The locus maps on the short arm of maize chromosome six near several other disease-resistance genes. Results indicate the same type of genes may contribute to both non-host resistance and resistance to pathogens.

Blotting, Northern↗

MgtC as a horizontally-acquired virulence factor of intracellular bacterial pathogens: evidence from molecular phylogeny and comparative genomics.

MgtC is a virulence factor required for intramacrophage survival and growth in low Mg2+ medium in two pathogens that are not phylogenetically related, Salmonella typhimurium and Mycobacterium tuberculosis. In S. typhimurium, mgtC is carried by the SPI-3 pathogenicity island and hybridization studies have suggested that the distribution of mgtC among enterobacteria is limited. In the present study, we searched for the presence of mgtC-like sequences in eubacterial genomes. Analyses of MgtC-like proteins phylogeny and mgtC-like chromosomal context support the hypothesis that mgtC has been acquired by horizontal gene transfer repeatedly throughout bacterial evolution. In addition, the phylogenetic analysis revealed the existence of a subgroup of proteins, that includes the S. typhimurium and M. tuberculosis MgtC proteins, as well as MgtC-related proteins from other pathogens that are able to survive in macrophages, B. melitensis and Y. pestis. We propose that MgtC has a similar function in all these distantly related pathogens, most likely providing the ability to grow in a low Mg2+ environment.

Amino Acid Sequence↗

Detection of microbial pathogens in shellfish with multiplex PCR.

Multiplex PCR amplification of uidA, cth, invA, ctx, and tl genes was developed enabling simultaneous detection in shellfish of Escherichia coli, an indicator of fecal contamination and microbial pathogens, Salmonella typhimurium, Vibrio vulnificus, V. cholerae, and V. parahaemolyticus, respectively. Each of the five pairs of oligonucleotide primers was found to support PCR amplifications of only its targeted gene. The optimized multiplex PCR reaction utilized a PCR reaction buffer containing 2.5 mM MgCl2 and primer annealing temperature of 55 degrees C. Oyster tissue homogenate seeded with these microbial pathogens was subjected to DNA purification by the Chelextrade mark 100 (BioRad) method. The sensitivity of detection for each of the microbial pathogens was </=10(1)-10(2) cells following a "double" multiplex PCR amplification approach. Amplified target genes in a multiplex PCR reaction were subjected to a colorimetric GeneCombtrade mark (BioRad) DNA-DNA hybridization assay. This assay was rapid and showed sensitivity of detection comparable to the agarose gel electrophoresis method. The colorimetric GeneCombtrade mark assay avoids use of hazardous materials inherent in conventional gel electrophoresis and radioactive-based hybridization methods. Multiplex PCR amplification, followed by colorimetric GeneCombtrade mark DNA-DNA hybridization, has been shown to be an effective, sensitive, and rapid method to detect microbial pathogens in shellfish.

Animals↗

Characterizing the symmetric equilibrium of multi-strain host-pathogen systems in the presence of cross immunity.

We investigate the population dynamics of host-pathogen systems in which the pathogen has a potentially arbitrary number of antigenically distinct strains interacting via cross-immunity. The interior equilibrium configuration of the symmetric multiple strain SIR model with cross-immunity is characterized. We develop an efficient iterative method for numerically solving the equilibrium equation together with a number of informative analytical approximations to the full solution. Equilibrium properties are studied as a function of the number of strains, reproduction number, infectious period, and cross immunity profile. We establish that the prevalence in the system increases monotonically with the number of strains and the reduction in cross immunity. Moreover, we demonstrate the existence of a phase transition separating high prevalence and low prevalence parameter regions, with the critical point being defined by sigmaR0 congruent with1, where sigma is the level of cross-immunity and R0 is the reproduction number. Above the threshold, prevalence saturates with increasing numbers of strains as a result of the inclusion of prohibition of co-infection in the model. Below the threshold, prevalence saturates much more rapidly as the number of strains increases--indicating that when cross-protection is sufficiently intense, the selective advantage for a pathogen to increase its diversity is substantially less than in the threshold region. Similarly, there is limited benefit to increased transmissibility (or decreased cross-immunity) both for the high and low diversity pathogen systems compared with systems at the threshold sigmaR0 congruent with1 where small increase in transmissibility can result in significant increase in prevalence.

Animals↗