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Emerging waterborne infections: contributing factors, agents, and detection tools.

Because microorganisms are easily dispersed, display physiological diversity, and tolerate extreme conditions, they are ubiquitous and may contaminate and grow in water. The presence of waterborne enteric pathogens (bacteria, viruses, and protozoa) in domestic water supplies represents a potentially significant human health risk. Even though major outbreaks of waterborne disease are comparatively rare, there is substantial evidence that human enteric pathogens that are frequently present in domestic water supplies are responsible for low-level incidence of waterborne microbial disease. Although these diseases are rarely debilitating to healthy adults for more than a few hours to a few days, enteric pathogens can cause severe illness, even death, for young children, the elderly, or those with compromised immune systems. As the epidemiology of waterborne diseases is changing, there is a growing global public health concern about new and reemerging infectious diseases that are occurring through a complex interaction of social, economic, evolutionary, and ecological factors. New microbial pathogens have emerged, and some have spread worldwide. Alternative testing strategies for waterborne diseases should significantly improve the ability to detect and control the causative pathogenic agents. In this article, we provide an overview of the current state of knowledge of waterborne microbial pathogens, their detection, and the future of new methods in controlling these infectious agents.

Adaptation, Physiological↗

The role of myeloperoxidase in the microbicidal activity of polymorphonuclear leukocytes.

Myeloperoxidase (MPO), H2O2 and a halide form a powerful antimicrobial system effective against bacteria, fungi, viruses and mammalian cells. After phagocytosis, MPO is released into the phagosome from adjacent granules where it interacts with H2O2 generated either by leukocytic or microbial metabolism and a halide such as chloride or iodide to form agents toxic to the ingested organisms. Evidence for H2O2 and MPO participation in the microbicidal activity of polymorphonuclear leukocytes (PMNs) has been obtained from patients with neutrophil dysfunction. In chronic granulomatous disease, PMNs have a microbicidal defect associated with the absence of the respiratory burst. The importance of H2O2 deficiency in the PMN dysfunction is emphasized by its reversal by H2O2. PMNs which lack MPO also have a major fungicidal and bactericidal defect. Bactericidal activity is particularly low during the early postphagocytic period, after which the organisms are killed. Although emphasizing the importance of MPO-mediated antimicrobial systems particularly during the early postphagocytic period, these findings also indicate the presence of MPO-independent systems which develop slowly but are ultimately effective. The MPO-independent antimicrobial systems may be oxygen-dependent or oxygen-independent. The acetaldehyde-xanthine oxidase system has been used as a model of the MPO-independent, oxygen-dependent antimicrobial systems of the PMN. A microbicidal effect by this system was observed which was inhibited by superoxide dismutase, catalase and scavengers of hydroxyl radicals (OH') and singlet oxygen (1O2). The microbicidal activity of acetaldehyde and xanthine oxidase is increased considerably by MPO and chloride. The formation of ethylene from methional or 2-oxo-4-methylthiobutyric acid by PMNs has been regarded as evidence for OH' formation. We have found ethylene formation to be largely dependent on MPO and evidence for the initiation of ethylene formation by 1O2 has been obtained. Both the xanthine oxidase system and the MPO-H2O2-halide system convert diphenylfuran into cis-dibenzoylethylene, an effect which is compatible with, although not proof of, the formation of 1O2 by these systems.

Blood Bactericidal Activity↗

Effects of preservatives, steroids, and ethylenediaminetetraacetate on the antimicrobial activity of sulfacetamide.

The effect of EDTA (ethylenediaminetetraacetate), steroids, and preservatives on the antimicrobial activity of 10% sodium sulfacetamide solutions was evaluated in this study by kill rate and minimum inhibitory concentration (MIC) using five representative microorganisms. The results indicate that thimerosal-preserved sulfacetamide solutions containing EDTA are more effective against Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus epidermidis, and Candida albicans than similar paraben-preserved solutions. Furthermore, the addition of EDTA improves the kill rate, but not the MIC, for the Pseudomonas, Serratia, and Candida species regardless of the preservative. The combination of a steroid with sulfacetamide does not affect its antimicrobial activity.

Anti-Infective Agents, Local↗

Comparative effects of selected phenothiazine tranquilizers and antihistaminics on bacterial cells and possible interactions with antibiotics.

Evaluation of the antibacterial effect of phenothiazine antihistaminics (trimeprazine, promethazine, and fonazine) and phenothiazine tranquilizers (promazine, chlorpromazine, triflupromazine, and propiomazine) on Staphylococcus aureus showed that tranquilizers were more active [minimum inhibitory concentration (MIC) 0.5-1.6 micrograms/mL] than antihistaminics (MIC greater than 1.6 micrograms/mL). The antibacterial activity was found to correlate with both the rate of adsorption of these drugs on the bacterial cells and the surface tension of their solutions. Phenothiazine tranquilizers caused rapid and extensive leakage of potassium ions from bacterial cells, while phenothiazine antihistaminics produced relatively slower leakage of these ions. A study of the effect of the phenothiazines on the antibacterial activity of some antibiotics showed that all phenothiazines produced a synergistic effect with erythromycin and an antagonistic effect with tobramycin. Variable effects were observed with chloramphenicol, and no effect was observed with penicillin. Results were explained on the basis of structural characteristics of the phenothiazines.

Adsorption↗

Instar susceptibility of the monarch butterfly (Danaus plexippus) to the neogregarine parasite, Ophryocystis elektroscirrha.

The susceptibility of the monarch butterfly (Danaus plexippus) larvae to the neogregarine parasite, Ophryocystis elektroscirrha, was tested in the laboratory. Spore loads recovered from infected monarch butterflies were directly related to the inoculum level, larval stage of the host, and spore age. There was a linear relationship between spores ingested by first instar larvae and spore concentration. Larvae feeding on leaves treated with 0, 50, 500, 5000, or 50,000 spores averaged 0, 0, 193, 457, or 1,255 spores, respectively, on the abdomens of the adult butterflies. When first, third, and fifth instar larvae were given 14.5 spores/mg of body weight, there was no significant difference in the spore load of the adults resulting from the first and third instars. However, there were significant differences in the spore load from adults resulting from the first and third instars versus the fifth instar. In addition, 1-year-old spores were not as infectious as fresh spores. Our findings indicate that under field conditions, the first instar is most likely to become infected because one spore appears sufficient to produce a detectable spore load in the adult. Older instars are less susceptible and have fewer opportunities to encounter sufficient viable spores for infection to occur. Thus, vertical transmission appears to be the primary mode of parasite maintenance in natural populations of monarch butterflies.

Animals↗

Role of the innate immune system and host-commensal mutualism.

Host organisms live in intimate contact with indigenous microflora. The interactions between the host and commensal microbiota are highly complex and heterogeneous. A growing body of evidence indicates that commensal symbionts provide many benefits to the host physiology, particularly in the gastrointestinal system. The molecular mechanisms of the mutualistic interactions between the host and commensals are largely unknown but can be due either to bioactivity of the commensals or to the reaction of the host immune system to the commensal-derived products. Recent advances in our understanding of the innate immune system allow re-evaluation of some of the older findings regarding the mechanisms of benefits conferred by microflora. Here we review the examples of the benefits of host-commensal interactions that are due to recognition of commensal microbial products by the host innate immune system.

Animals↗

Modification of experimental colon carcinogenesis by dietary fibers.

The literature concerning the effect of individual dietary fibers on the experimental induction of colorectal cancer was reviewed. It has become increasingly apparent that the effect of dietary fibers on colon carcinogenesis depends on many factors, including the type and amount of fiber; the other dietary components, particularly fat; animal species, strain, and sex; and the type of carcinogen and its dose and route of administration. Despite such variations in design, most experiments with wheat bran and cellulose have shown evidence of a significant protective effect. In contrast, numerous other fiber supplements have been shown to enhance tumor development. These include pectin, corn bran, undegraded carageenan, agar, Metamucil, and alfalfa. Possible mechanisms by which fibers may inhibit colon tumorigenesis include dilution and adsorption of any carcinogens or promoters contained within the intestinal lumen and faster transit time and therefore less opportunity for carcinogen/promoter interaction with the intestinal epithelium. Modulation of colonic microbial metabolic activity by dietary fibers may also be important in the activation and detoxification of carcinogens and promoters. Dietary fibers produce structural and functional changes in the intestinal epithelium and modify rates of cell proliferation changes in the intestinal epithelium and modify rates of cell proliferation and migration. Evidence suggests that if this stimulus to cell proliferation occurs during the stage of initiation, it may lead to enhancement of the carcinogenic process. Dietary fibers bind not only carcinogens, bile acids, and other potentially toxic agents but also essential nutrients that themselves can modify the carcinogenic process. Fermentation of fibers within the large bowel results in production of volatile fatty acids, which in vitro have been shown to be antineoplastic. Fermentation also produces a lower luminal pH, which in turn affects colonic microbial populations and their metabolic activities. The presence of lignans in higher plants and their bacterial synthesis from precursors present in fiber-rich foods provide an additional source of antineoplastic agents, whose relative importance in colon carcinogenesis is unknown. Because dietary fibers differ in their physiochemical properties, it has been difficult to identify a single mechanism by which fibers prevent or inhibit colon carcinogenesis. Clearly, more investigation is needed regarding the mechanism(s) by which certain fibers inhibit while others enhance experimental colon carcinogenesis.

Animals↗

Antifungal activity of ovotransferrin towards genus Candida.

The inhibiting activity of ovotransferrin was tested towards different species belonging to genus Candida. Of one hundred strains tested, only C. krusei showed a noticeable resistance, while the other species appeared to be more sensitive than bacteria to the action of ovotransferrin. The influence of anions, such as bicarbonate and citrate, on the inhibiting activity of ovotransferrin was also investigated. Moreover it was observed that iron saturated ovotransferrin retained its activity, thus suggesting an interaction between the protein and Candida cells.

Antifungal Agents↗

In vitro interaction between the penem FCE 22101 and ceftazidime.

FCE 22101, a penem antimicrobial agent, was found to resist hydrolysis by bacterial beta-lactamases and to have a strong affinity for Type Ia enzymes. Like imipenem, FCE 22101 was shown to be capable of inducing resistance to a wide range of beta-lactam antibiotics. FCE 22101 antagonized the in vitro activity of ceftazidime against enteric bacilli that commonly produce inducible enzymes. This penem should not be combined with other beta-lactams for chemotherapeutic purposes.

Anti-Bacterial Agents↗

Structure and biological actions of lactoferrin.

Lactoferrin is an iron-binding glycoprotein of the transferrin family, first isolated from milk but also found in most exocrine secretions as well as in the secondary granules of neutrophils. The many reports on its antimicrobial and antiinflammatory activity in vitro identify lactoferrin as important in host defense against infection and excessive inflammation. Most if not all lactoferrin actions are mediated through iron sequestration and/or interaction with a large variety of ligands including microbial cell wall components and cellular receptors, through its highly positively charged N-terminus. Lactoferrin exerts its effects on glandular epithelia, secretions, mucosal surfaces as well as in the interstitium and vascular compartments where it has been postulated to participate in iron metabolism, disease defense, and modulation of inflammatory and immune responses. A need to understand the diverse biological actions of lactoferrin and the prospect of a wide variety of potential applications in human health care have stimulated studies of the relation between lactoferrin structure and function, the regulation of lactoferrin secretion and development of large scale production of recombinant human lactoferrin (hLf). This review provides a synthesis of our current understanding of lactoferrin. Space limitations have led us to refer to review articles whenever possible; the reader is advised to use these articles for access to the primary experimental literature.

Anti-Infective Agents↗

In vitro effects of essential oils from Ostericum koreanum against antibiotic-resistant Salmonella spp.

The essential oil fraction of Ostericum koreanum was analyzed by GC-MS. Inhibiting activities of this oil and its main components were tested by the broth dilution assay and disk diffusion test against one antibiotic-susceptible and two resistant strains of Salmonella enteritidis and S. typhimurium, respectively. The GC-MS analysis revealed thirty-four compounds; the main components were alpha-pinene (41.12%), rho-cresol (17.99%) and 4-methylacetophenone (7.90%). The essential oil of O. koreanum and its main components were significantly effective against the tested antibiotic-susceptible strains as well as against the resistant strains of the two Salmonella species, with MICs (minimum inhibitory concentrations) ranging from 2 mg/mL to 16 mg/mL. The anti-Salmonella effects of the oils were dose-dependent on Müller-Hinton agar plates in this experiment. Additionally, checkerboard titer test results demonstrated significant combined effects of streptomycin and O. koreanum oil or cresol, one of the main components of this oil, against the two streptomycin resistant strains of S. typhimurium, with FICIs ranging from 0.12 to 0.37.

Anti-Bacterial Agents↗

Plasmodium berghei: diet and drug dosage regimens influencing selection of drug-resistant parasites in mice.

Two different diets for the host and three drug dosage regimens were used to select lines resistant to sulfadoxine and pyrimethamine from the parent strain of the rodent malaria parasite Plasmodium berghei [the N (K173) strain]. A higher yield of resistance was obtained when a high parasitemia was present at the beginning of the drug pressure schedule. The development of resistance to the association of sulfadoxine plus pyrimethamine was accelerated by a relatively high para-aminobenzoic acid (PABA) content diet. Reproducibility was satisfactory when one of the dosage regimens was applied independently by two different technicians at different times.

4-Aminobenzoic Acid↗

The growth of pure and simple microbial competitors in a moving distributed medium.

The dynamics of pure and simple competition between two microbial species are examined for the case of interaction arising in a distributed and nonstagnant environment. The environment is modeled as a tubular reactor. It is shown that for relatively small values of the dispersion coefficient (i.e., for small, but nonzero, backmixing of the medium), the two competing populations can coexist in a stable steady state. It has been assumed that the species grow uninhibited and that if there are maintenance requirements they are satisfied from endogenous sources. From numerical studies it has been found that a necessary condition for coexistence is that the net specific growth rate curves of the two competitors cross each other at a positive value of the concentration of the rate-limiting substrate. The model equations have been numerically solved by using the methods of orthogonal and spline collocation.

Animals↗

The symbiotic microbial community of the Sonoran Desert termite: Pterotermes occidentis.

Pterotermes occidentis is a large, obscure, very primitive dry wood termite limited to the Sonoran desert of North America. Its development, caste system and behavior are discussed in relation to aspects of its ecology. What appear to be single wood-digesting individual termites are in fact insect hosts which harbor extensive microbial communities estimated to contain more than 40 interacting species. All healthy, wood-eating Pterotermes contain these densely populated communities of highly motile symbionts suggesting that species diversity is necessary for termite survival. A morphological catalogue of the major hindgut microbes is presented here. From 10(7) to 10(11) bacteria and from 10(3) to 10(6) protists/ml of hindgut fluid are found in an average nymph or larva. The species of four wood-ingesting mastigotes (genera Trichonympha, Metadevescovina, Tricercomitus and Microrhopalodina) and nearly 30 morphologically distinct types of bacteria are described. The description of this morphological diversity observed with light, scanning and transmission electron microscopy is a prerequisite to functional analyses of the symbioses. Since Pterotermes is easily maintained in the laboratory and is so large it is hoped that it will provide a useful model for symbiosis research.

Animals↗

Antistaphylococcal activity of amoxicillin and ticarcillin when combined with clavulanic acid. Evaluation of oxacillin-resistant and oxacillin-susceptible isolates.

The beta-lactamase inhibitor, clavulanic acid, was combined with amoxicillin and with ticarcillin for in vitro studies with 586 staphylococci: 97 stock cultures of oxacillin-resistant strains recovered before 1982, and 489 blood or wound isolates collected from 40 separate medical centers during 1987-1988 (300 were oxacillin resistant). Over 92% of the staphylococci produced beta-lactamase enzymes and were thus resistant to both penicillins. However, with the addition of clavulanic acid, oxacillin-susceptible strains were rendered susceptible to low concentrations of amoxicillin and ticarcillin. Staphylococcus aureus strains with borderline or partial borderline resistance to penicillinase-resistant penicillins occurred infrequently (72 of 325 S. aureus isolates). Those strains were susceptible to both clavulanic acid combinations, because their methicillin resistance is thought to be due to an excess beta-lactamase production. Strains with chromosomally mediated intrinsic heteroresistance were relatively resistant to both drug combinations. Minimal inhibitory concentration (MIC) breakpoints that best separated those heteroresistant strains from oxacillin-susceptible isolates were as follows: amoxicillin/clavulanic acid, less than or equal to 2.0/1.0 micrograms/ml for susceptible; and ticarcillin/clavulanic acid, less than or equal to 4.0/2.0 micrograms/ml for susceptible. When the broth was supplemented by 2% NaCl, MICs for both drug combinations were increased by less than one doubling dilution. Although oxacillin and methicillin broth microdilution tests were more reliable when 2% NaCl was added, tests with the two drug combinations were only minimally improved by adding 2% NaCl to the broth medium.

Amoxicillin↗

Iron acquisition in microbial pathogenesis.

Successful competition for iron by potential pathogens is essential to establish infection. The roles of the various types of microbial iron acquisition systems in host-pathogen interactions depend on the nature of the infection and the location of the pathogen within the host. Microbes infecting the extracellular spaces of the host employ different strategies for iron acquisition than those that invade and multiply within host cells.

Animals↗

Commensals upon us.

A battle to control and curtail bacterial infectious diseases is being waged in our hospitals and communities through antibiotic therapies and vaccines targeting specific species. But what effects do these interventions have on the epidemiology of infections caused by the organisms that are part of our natural microbial flora? Gram-positive and gram-negative bacteria appear as new disease agents from among commensal flora. These include vancomycin resistant enterococci (VRE), community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), non-vaccine invasive serotypes of Streptococcus pneumoniae, new strains of non-type b Haemophilus influenzae and multi-drug resistant Escherichia coli. These examples illustrate how clinical improvements and widespread use and misuse of antibiotics have pushed evolution, allowing normally non-pathogenic strains to become infectious disease threats to human health.

Anti-Bacterial Agents↗

Potent DNA gyrase inhibitors; novel 5-vinylpyrazole analogues with Gram-positive antibacterial activity.

In this study, we designed and synthesized novel 5-vinylpyrazole analogues by decreasing the lipophilicity of the parent compounds 1a,b; 3-[(3-methoxycarbonyl)cyclohexylaminomethyl]indazoles while keeping the van der Waals interaction with the lipophilic area of DNA gyrase B. The selected compound 8bb exhibited good antibacterial activity against staphylococci and enterococci, including multi-drug resistant strains.

Anti-Bacterial Agents↗