Staphylococcus aureus has long been recognized as an important pathogen in human disease. Due to an increasing number of infections caused by methicillin-resistant S. aureus (MRSA) strains, therapy has become problematic. Therefore, prevention of staphylococcal infections has become more important. Carriage of S. aureus appears to play a key role in the epidemiology and pathogenesis of infection. The ecological niches of S. aureus are the anterior nares. In healthy subjects, over time, three patterns of carriage can be distinguished: about 20% of people are persistent carriers, 60% are intermittent carriers, and approximately 20% almost never carry S. aureus. The molecular basis of the carrier state remains to be elucidated. In patients who repeatedly puncture the skin (e.g., hemodialysis or continuous ambulatory peritoneal dialysis [CAPD] patients and intravenous drug addicts) and patients with human immunodeficiency virus (HIV) infection, increased carriage rates are found. Carriage has been identified as an important risk factor for infection in patients undergoing surgery, those on hemodialysis or CAPD, those with HIV infection and AIDS, those with intravascular devices, and those colonized with MRSA. Elimination of carriage has been found to reduce the infection rates in surgical patients and those on hemodialysis and CAPD. Elimination of carriage appears to be an attractive preventive strategy in patients at risk. Further studies are needed to optimize this strategy and to define the groups at risk.

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Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks.

worked for the smallpox eradi-cation programme in western Africa in 1962-1963 as a member of the staff of the W H O Regional Office for Africa. In 1964 he was transferred t o W H O Headquarters in Geneva, and in 1966 he joined the Smallpox Eradication unit, of which he was Chief from 1977 until 1984. He is now Director of the Kumamoto National Hospital in Japan and a member of the advisory group on international health of the Ministry of Health and Welfare of Japan. while at the Communicable Disease Center in the USA, was responsible in 1965-1 966 for the planning of the western and central African smallpox eradication-measles control programme, conducted with the support of the United States Agency for International Development. USSR from 1983 until his death in 1987. T h e authors alone are responsible for t h e views expressed i n t h i s publication. The World Health Organization welcomes such applications. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

Smallpox and its eradication

Slime production is not a generally recognized feature of Staphylococcus epidermidis. In a recent outbreak of S. epidermidis intravascular catheter-associated sepsis, we noted that 63% of clinically implicated strains grew as a slimy film coating the culture tube walls when propagated in tryptic soy broth. Only 37% of randomly collected blood culture contaminants and skin isolates demonstrated a similar phenomenon (p less than 0.05). Transmission electron micrographs of these coating bacteria showed them to be encased in an extracellular matrix that stained with alcian blue. Slime production was most evident in autoclaved media containing Casamino Acids and glucose supplementation (0.25% wt/vol). There were strain and media preparation variability of slime production in the presence of other carbohydrates. Some strains were not able to produce slime under any of the tested conditions. The production or nonproduction of slime did not influence growth rate. When grown in vitro, slime producers accumulated on the surface of intravascular catheters as macrocolonies, whereas non-slime, producers did not. Transmission and scanning electron micrographs showed slime producers to be encased in an adhesive layer on the catheter surface, whereas nonproducers were not encased. These results suggest that slime-mediated adherence may be a critical factor in the pathogenesis of S. epidermidis infections of medical devices.

Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces.

The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes.

The nucleoids of Escherichia coli, independently of the physiological state of the bacteria, are shown to be preserved as a fine-stranded fibrillar nucleoplasm by an OsO(4) fixation under defined conditions: acetate-veronal buffer pH 6, presence of Ca(++) and amino acids, stabilization with uranyl-acetate before dehydration. The same fixation procedure applied to the DNA of vegetative phage reveals a pool of homogeneous fibrillar structure very similar to the nucleoplasm. The "versene test," which produces a coarse coagulation of these plasms, emphasizes the similar behaviour of the pool and the nucleoids. The heads of mature phage are preserved in their true polyhedral shape by the standard fixation procedure, although they may be badly distorted when fixed under different conditions. Lanthanum nitrate and uranyl-acetate are shown to increase markedly the contrast of both phage and cytoplasm. The consequences of the fibrillar structure of the genetic material are discussed in relation to the probable division process.

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Electron microscope study of DNA-containing plasms. II. Vegetative and mature phage DNA as compared with normal bacterial nucleoids in different physiological states.

Summary Procedure and apparatus for the preservation of biological products in lyophile form have been described in detail. The method is one of rapid freezing and rapid dehydration from the frozen state. The product is vacuum sealed in the final container in which it is to be stored and distributed. The apparatus is simple in operation. Models have been described for use in research laboratories, for board of health and hospital work and for industrial scale production. Normal and convalescent human sera, animal antisera and complement, miscellaneous proteins, enzymes, viruses, bacteria and other materials have been preserved. Complement may be preserved without detectable deterioration for at least ten months, and indications are that many types of antisera may probably be preserved unaltered for an indeterminate number of years.

Procedure and Apparatus for Preservation in " Lyophile " Form of Serum and Other Biological Substances.

Although the mechanism of antibody formation has naturally been a principal problem of immunology from its beginning, it remains still unsolved. Even a tentative hypothesis, giving a rational chemical picture of how antibody formation may occur should at least serve to focus though t and suggest experiment upon this problem. It would seem that the specific correspondence of antigen and antibody can best be explained by some sort of directing mechanism in antibody synthesis. A hypothesis involving such a mechanism ishere proposed and certain of its implications are pointed out. “By definition an antigen is any substance which, introduced into the tissues orcirculating fluids of an animal, causes the appearance in these fluids, sooner or later, of substances which react specifically with the antigenic substance; i.e., specific antibodies” (1). The essential fact to be explained is that every or nearly every known sort of soluble protein which contains its full quota of amino acids is antigenic, i.e., gives rise on injection to antibodies which possess specific elective combining affinity with itself.

A Hypothetical Mechanism of Antibody Formation

The granules which are so readily demonstrable in mycobacteria were interpreted by Robert Koch (1884) as spores.4 More recently they have been interpreted, with minor variations, as reserve particles, fat droplets, degeneration products, reproductive (Much) granules, conidia, gonidia, \"sporide,\" and nuclei. The literature has been well reviewed among others by Wessel (1942), Knaysi (1929), and Knaysi, Hillier, and Fabricant (1950). The present work demonstrates that these granules are loci of enzymatic oxidative-reductive activities, contain phospholipid, and give in high dilutions of Janus green B the succession of colors characteristic for the staining of mitochondria. The granules have smooth spheroidal to ellipsoidal contours and, except when deformed by adjacent structures, have surfaces of minimal areas. When the granules have been volatilized by intense electronic bombardment, definite limiting surface membranes remain. The essential attributes of these granules are characteristic of the mitochondria of the cells of higher animals and plants.

Evidence suggesting that the granules of mycobacteria are mitochondria.

The dark-field microscope may be used to observe directly the characteristics of composite films. The liquid phases, one or both of them containing suspended solid particles as test objects (in these experiments bacteria were used), are spread between slide and cover-glass and examined with any desired lenses. The liquid-liquid interfaces appear as bright lines and the solid particles as shining motes. An interfacial kinetic mechanism has been observed in films of all composition studied. The bacteria are transported along the phase boundary lines in a striking and characteristic manner and quite independently of movements in the adjoining organic or aqueous phases. These movements in the interface are interpreted as essentially due, according to the composition of the films, to local inequalities in interfacial surface tension, or to minute currents from mixing of the two phases across and along their boundary line, or to both forces acting together. The bacteria (non-motile in these experiments) reached the interface by brownian movement or currents or shifts in the position of the boundary line. Once in the interface they tended to remain, and accumulated there, in instances where the liquid-liquid interfacial tension was high at least, in higher concentration than in the contiguous phases. Bacteria could, however, escape from the interface in a variety of ways detailed above. With liquids which differ markedly in interfacial tension and miscibility with water, these properties may be correlated with the characteristics of the preparation. With cyclohexane-water films, for instance, (immiscible, interfacial tension high), the boundary was less readily drawn out into projections, the interfacial trapping mechanism was more efficient, and brownian movement of bacteria in the interface was less free than with cyclohexanol-water films (miscible, interfacial tension low). Analysis of the mechanism of the phenomena herein described will be given in the paper following.

https://rupress.org/jem/article-pdf/40/5/633/1177060/633.pdf

The penetration of bacteria through capillary spaces : iv. a kinetic mechanism in interfaces.

Evidence is accumulating to suggest that in yeasts polyphosphates furnish both phosphorus and energy required for nucleic acid synthesis. A cyclic interrelationship between polyphosphate accumulation and utilization on the one hand and growth and cell division on the other is beginning to be discernible in yeasts (Chayen et al., 1955; Schmidt et al., 1956); and in the mold Aspergillus niger, (Krishnan et al., 1957). See also Esposito and Wilson (1956). A reciprocal relationship between the intracellular distribution of phosphorus in polyphosphates and in ribonucleic acid (RNA) of Corynebacterium diphtheriae was found by Sall et al. (1956). Polyphosphate accumulation and disappearance in a species of Mycobacterium were found to respond to metabolic conditions in a pattern similar to that in Corynebacterium (Mudd et al., 1956). Synthesis of nucleic acids has recently been shown in cultures of bacteria dividing synchronously to be a discontinuous process (Scott et al., 1956), whereas respiration is a continuous process. The possibility is suggested, therefore, that accumulation and utilization of polyphosphates may be intimately concerned in the cyclic metabolism of energy and of building materials in bacterial growth and cell division. It seems important to explore these possibilities much further. In the present study the exchange of phosphorus between RNA and polyphosphate (metaphosphate) in Mycobacteria is confirmed under particular metabolic conditions, and in the presence of dinitrophenol and azaserine as inhibitors. A second focus of interest in this study has been a comparison of the information yielded

Stuart Mudd

Papers

Procedure and Apparatus for Preservation in " Lyophile " Form of Serum and Other Biological Substances.

A Hypothetical Mechanism of Antibody Formation

Evidence suggesting that the granules of mycobacteria are mitochondria.

The penetration of bacteria through capillary spaces : iv. a kinetic mechanism in interfaces.

Polyphosphate as accumulator of phosphorus and energy.