Iron uptake mechanisms of pathogenic bacteria

Abstract: Most of the iron in a mammalian body is complexed with various proteins. Moreover, in response to infection, iron availability is reduced in both extracellular and intracellular compartments. Bacteria need iron for growth and successful bacterial pathogens have therefore evolved to compete successfully for iron in the highly iron-stressed environment of the host's tissues and body fluids. Several strategies have been identified among pathogenic bacteria, including reduction of ferric to ferrous iron, occupation of intracellular niches, utilisation of host iron compounds, and production of siderophores. While direct evidence that high affinity mechanisms for iron acquisition function as bacterial virulence determinants has been provided in only a small number of cases, it is likely that many if not all such systems play a central role in the pathogenesis of infection.     

Virulence mechanisms of Gram-positive plant pathogenic bacteria

Actinobacteria and Firmicutes comprise a group of highly divergent prokaryotes known as Gram-positive bacteria, which are ancestral to Gram-negative bacteria. Comparative genomics is revealing that, though plant virulence genes are frequently located on plasmids or in laterally acquired gene clusters, they are rarely shared with Gram-negative bacterial plant pathogens and among Gram-positive genera. Gram-positive bacterial pathogens utilize a variety of virulence strategies to invade their plant hosts, including the production of phytotoxins to allow intracellular and intercellular replication, production of cytokinins to generate gall tissues for invasion, secretion of proteins to induce cankers and the utilization and manipulation of sap-feeding insects for introduction into the phloem sieve cells. Functional analysis of novel virulence genes utilized by Actinobacteria and Firmicutes is revealing how these ancient prokaryotes manipulate plant, and sometimes insect, metabolic processes for their own benefit.     

Molecular-genetic mechanisms of antigenic variability of pathogenic bacteria

The literature on the molecular genetic mechanisms for antigenic variability of pathogenic bacteria is reviewed. Ability to antigenic variability in any case discussed is considered to be a pathogenicity factor permitting efficient struggle against the immune system of the host-organism. The molecular basis for such variability is instability of the genome structure, coding for highly immunogenic bacterial proteins.     

Neuronal mechanisms of Caenorhabditis elegans and pathogenic bacteria interactions

Individuals interact with environment through different neuronal functions, such as olfaction and mechanosensation; experience shapes these physiological functions. It is not well understood how an individual senses and processes multiple cues of natural stimuli in the environment and how experience modulates these physiological mechanisms. Recent molecular genetics and behavioral studies on the interactions of the genetic model organism Caenorhabditis elegans with pathogenic bacteria have provided insights on the molecular and cellular mechanisms underlying these regulatory processes.     

Endobiotic bacteria and their pathogenic potential in cnidarian tentacles

Endobiotic bacteria colonize the tentacles of cnidaria. This paper provides first insight into the bacterial spectrum and its potential of pathogenic activities inside four cnidarian species. Sample material originating from Scottish waters comprises the jellyfish species Cyanea capillata and C. lamarckii, hydrozoa Tubularia indivisa and sea anemone Sagartia elegans. Mixed cultures of endobiotic bacteria, pure cultures selected on basis of haemolysis, but also lyophilized samples were prepared from tentacles and used for DGGE-profiling with subsequent phylogenetic analysis of 16S rDNA fragments. Bacteria were detected in each of the cnidarian species tested. Twenty-one bacterial species including four groups of closely related organisms were found in culture material. The species within these groups could not be differentiated from each other (one group of Pseudoalteromonas spp., two groups of Shewanella spp., one group of Vibrio spp.). Each of the hosts exhibits a specific endobacterial spectrum. Solely Cyanea lamarckii harboured Moritella viscosa. Only in Cyanea capillata, members of the Shewanella group #2 and the species Pseudoalteromonas arctica, Shewanella violacea, Sulfitobacter pontiacus and Arcobacter butzleri were detected. Hydrozoa Tubularia indivisa provided an amazingly wide spectrum of nine bacterial species. Exclusively, in the sea anemone Sagartia elegans, the bacterial species P. aliena was found. Overall eleven bacterial species detected were described recently as novel species. Four 16S rDNA fragments generated from lyophilized material displayed extremely low relationship to their next neighbours. These organisms are regarded as members of the endobiotic “terra incognita”. Since the origin of cnidarian toxins is unclear, the possible pathogenic activity of endobiotic bacteria has to be taken into account. Literature data show that their next neighbours display an interesting diversity of haemolytic, septicaemic and necrotic actions including the production of cytotoxins, tetrodotoxin and R-toxin. Findings of haemolysis tests support the literature data. The potential producers are Endozoicimonas elysicola, Moritella viscosa, Photobacterium profundum, P. aliena, P. tetraodonis, Shewanella waksmanii, Vibrio splendidus, V. aestuarius, Arcobacter butzleri.     

Lessons from signature-tagged mutagenesis on the infectious mechanisms of pathogenic bacteria

Studies on the genetic basis of bacterial pathogenicity have been undertaken for almost 30 years, but the development of new genetic tools in the past 10 years has considerably increased the number of identified virulence factors. Signature-tagged mutagenesis (STM) is one of the most powerful general genetic approaches, initially developed by David Holden and colleagues in 1995, which has now led to the identification of hundreds of new genes requested for virulence in a broad range of bacterial pathogens. We have chosen to present in this review, the most recent and/or most significant contributions to the understanding of the molecular mechanisms of bacterial pathogenicity among over 40 STM screens published to date. We will first briefly review the principle of the method and its major technical limitations. Then, selected studies will be discussed where genes implicated in various aspects of the infectious process have been identified (including tropism for specific host and/or particular tissues, interactions with host cells, mechanisms of survival and persistence within the host, and the crossing of the blood brain barrier). The examples chosen will cover intracellular as well as extracellular Gram-negative and Gram-positive pathogens.     

AIDS dementia and HIV-1-induced neurotoxicity: Possible pathogenic associations and mechanisms

AIDS Dementia Complex (ADC) is a syndrome of cognitive, behavioral, and motor deficits resulting from HIV-1 infection within the brain. ADC is characterized by variable degrees of neuronal cell death and gliosis that likely result, at least, in part from release of metabolic products, cytokines, and viral proteins from infected macrophages, although a unifying explanation for the neurological dysfunction has yet to be established. Major unanswered questions include: (i) do neurologic symptoms result from neuronal cell death and/or dysfunction in surviving neurons?; (ii) are viral genomic sequences determinants of neurotoxicity?; (iii) is HIV infection of neurons and astrocytes relevant to pathogenesis?, and (iv) what circulating factors within the brain affect neuronal cell survival and function? This review addresses the association between HIV-1 replication within the brain, production of potential neurotoxins and possible mechanisms of induction of neurotoxicity and neuronal dysfunction contributing to the pathogenesis of ADC.     

Proteomic analysis of a drosophila IBMPFD model reveals potential pathogenic mechanisms

IBMPFD, Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia, is a hereditary degenerative disorder due to single missense mutations in VCP (Valosin-Containing Protein). The mechanisms of how mutations of VCP lead to IBMPFD remain mysterious. Here we utilize two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry to study the IBMPFD disorder at the protein level. With this set-up, we are able to employ comparative proteomics to analyze IBMPFD disease using Drosophila melanogaster as our disease model organism. Head proteome of transgenic D. melanogaster expressing wild type VCP is compared, respectively, with the head proteome of transgenic mutant type VCPs that correspond to human IBMPFD disease alleles (TER94(A229E), TER94(R188Q), and TER94(R152H)). Of all the proteins identified, a significant fraction of proteins altered in TER94(A229E) and TER94(R188Q) mutants belong to the same functional categories, i.e. apoptosis and metabolism. Among these, Drosophila transferrin is observed to be significantly up-regulated in mutant flies expressing TER94(A229E). A knock-down experiment suggests that fly transferrin might be a potential modifier in IBMPFD disease. The molecular analysis of IBMPFD disease may benefit from the proteomics approach which combines the advantages of high throughput analysis and the focus on protein levels.     

Possible mechanisms of dendritic potential habituation in the cat association cortex

The effect of application of strychnine and calcium and of post-tetanic potentiation on the dynamics of gradual decay of dendritic potentials in the association cortex, which is regarded as monosynaptic habituation, was studied in acute experiments on cats anesthetized with pentobarbital. Despire a significant increase in amplitude of dendritic potentials after strychnine application or calcium enrichment of the physiological saline, the time course of habituation was unchanged. The course of habituation also remained unchanged during post-tetanic potentiation. It is concluded that habituation of dendritic potentials is due to processes taking place in the postsynaptic dendrite membrane itself and is independent of postsynaptic inhibition or transmitter exhaustion in presynaptic endings.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 208–213, March–April, 1984.     

Possible pathogenic mechanisms on trimethyltin-induced lesions in the hippocampus of adult and neonatal rats

The extent of trimethyltin (TMT) induced lesions in the rat hippocampal formation was reviewed. Adult rats were treated with a single dose of 6.0 mg TMT/kg body wt and were sacrificed between 3–60 d following exposure. In the hippocampal formation, the granule cells of fascia dentata showed early changes, which subsided considerably at a later time of the intoxication. On the other hand, destruction of the pyramidal neurons in the Ammon’s horn became more pronounced with time, resulting in an extensive destruction of this structure. It is interesting to note that the CA₃ neurons in the septal portion of the Ammon’s horn were more vulnerable than those located more temporally, whereas the reverse pattern was observed for the dentate granule cells as well as for the CA_1,2 neurons of the Ammon’s horn. Special stain for zinc (Timm’s method) also revealed a progressive depletion of zinc in the mossy fibers. When neonatal rats were treated at various times with a single injection of TMT, rapid and progressive destruction of the Ammon’s horn was observed in animals injected between postnatal day (PND) 5–15. The progression of neuronal involvement was CA_3b →CA_{3a, b} →CA_3(a,b,c)→CA₃+CA₂→entire Ammon’s horn (CA_1,2,3). This pattern of pathological lesion was in good concert with morphological development and functional maturity of the hippocampal formation. Destruction of the Ammon’s horn neurons was proposed to be the result of hyperexcitation of the dentate granule neurons under the influence of TMT. Other possible mechanisms are also discussed. Author to whom all correspondence and reprint requests should be addressed.     

Structural analysis of lipopolysaccharides from Gram-negative bacteria

This review covers data on composition and structure of lipid A, core, and O-polysaccharide of the known lipopolysaccharides from Gram-negative bacteria. The relationship between the structure and biological activity of lipid A is discussed. The data on roles of core and O-polysaccharide in biological activities of lipopolysaccharides are presented. The structural homology of some oligosaccharide sequences of lipopolysaccharides to gangliosides of human cell membranes is considered.     

Sialic acid-containing lipopolysaccharides in purple nonsulfur bacteria

Lipopolysaccharides (LPS) from a number of purple nonsulfur bacteria and of phylogenetically related species were analyzed for the presence of sialic acid by gas chromatography/mass spectrometry. Species and strains of the genera Rhodobacter, Rhodopseudomonas, Rhodomicrobium, Rhodospirillum, Rhodocyclus and Rhodopila were investigated, sialic acid, however, was found only in the genus Rhodobacter. It occurs in strains of Rhodobacter capsulatus, R. sphaeroides, R. sulfidophilus and R. veldkampii. All these species belong to the -3 subgroup of purple bacteria as defined by 16S rRNA catalogues. Approximately equimolar ratios of sialic acid and of 2-keto-3-deoxy-octonate (KDO) were found in isolated LPSs. Sodium deoxycholate gel electrophoresis of these LPS-samples also suggested a location of sialic acid in the LPS core region. Sialic acid was present only in those LPSs, which exhibited a complete core region.Abbreviations LPS Lipopolysaccharide - Neu5Ac N-acetylneuraminic acid - KDO 2-Keto-3-deoxy-octonate - Neuß2Me neuraminic acid-2-methyl glycoside - DOC sodium deoxycholate - PAGE polyacrylamide gel electrophoresis - HPLC high performance liquid chromatography - TLC thin layer chromatography     

Occurrence and pathogenic potential of Bacillus cereus group bacteria in a sandy loam

The major part (94%) of the Bacillus cereus-like isolates from a Danish sandy loam are psychrotolerant Bacillus weihenstephanensis according to their ability to grow at temperatures below 7 °C and/or two PCR-based methods, while the remaining 6% are B. cereus. The Bacillus mycoides-like isolates could also be␣divided into psychrotolerant and mesophilic isolates. The psychrotolerant isolates of B. mycoides could␣be discriminated from the mesophilic by the two PCR-based methods used to characterize B.␣weihenstephanensis. It is likely that the mesophilic B. mycoides strains are synonymous with Bacillus pseudomycoides, while psychrotolerant B. weihenstephanensis, like B. mycoides, are B. mycoides senso stricto. B. cereus is known to produce a number of factors, which are involved in its ability to cause gastrointestinal and somatic diseases. All the B. cereus-like and B. mycoides like isolates from the sandy loam were investigated by PCR for the presence of 12 genes encoding toxins. Genes for the enterotoxins (hemolysin BL and nonhemolytic enterotoxin) and the two of the enzymes (cereolysin AB) were present in the major part of the isolates, while genes for phospolipase C and hemolysin III were present in fewer isolates, especially among B. mycoides like isolates. Genes for cytotoxin K and the hemolysin II were only present in isolates affiliated to B. cereus. Most of the mesophilic B. mycoides isolates did not possess the genes for the nonhemolytic enterotoxin and the cereolysin AB. The presence of multiple genes coding for virulence factors in all the isolates from the B. cereus group suggests that all the isolates from the sandy loam are potential pathogens.     

Antibacterial potential of some Saudi honeys from Asir region against selected pathogenic bacteria

Honey is a nutrient rich natural product and has been utilized as traditional and complementary medicine since ancient times. In this study, antibacterial activity of Sider (Ziziphus spina-christi), Dharm (Lavandula dentata), and Majra (Hypoestes forskaolii) honey samples collected from Asir region of Saudi Arabia was in vitro evaluated at 80% and 50% w/v concentrations against five pathogenic bacteria i.e. Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Shigella flexneri, and Staphylococcus epidermidis. Well diffusion assays to measure the average zone of inhibition (ZOI) and minimum inhibitory concentration (MIC) values were employed in the experiments. All the tested honey samples showed antibacterial activity in a dose-dependent manner. Sider and Dharm exhibited a good antibacterial activity at high concentrations while, Majra honey of Apis mellifera jemenitica and of Apis florea showed comparatively low antibacterial activity. The average MIC values of Sider, Dhram from Rijal Alma, Dharm from Al-Souda, Majra (A.m. jemenitica), and Majra (A. florea) honey against all tested bacteria were 22%, 16%, 18%, 32%, and 28% (v/v) respectively. Dharm and Sider honeys showed better antibacterial activity than Majra honey. Saudi honey can be considered as a promising future antimicrobial agent and should be further investigated as an alternative candidate in the management of resistant bacterial pathogens.