The effect of oxygen-dependent antimicrobial systems on strains of<i>Legionella pneumophila</i>of different virulence

Jepras, Robert; Fitzgeorge, R. B.

doi:10.1017/s0022172400064354

Cited by 21 publications

(13 citation statements)

References 37 publications

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“…L. pneumophila is susceptible to both the myeloperoxidase and xanthine oxidase pathways in cell-free systems (164,165), a susceptibility that may explain the limited bactericidal capacity of human PMNL (139) and the initial killing of a portion of the inoculum by monkey macrophages (141). Jepras and Fitzgeorge noted that virulent strains were resistant to killing by the xanthine oxidase system, whereas less virulent isolates were killed (142). Other investigators have found the two systems equally effective against avirulent and virulent isolates (165), so the issue remains unresolved.…”

Section: Microbiology and Immunologymentioning

confidence: 99%

Legionnaires disease: historical perspective

1988

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In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae. In retrospect, members of the family had been isolated from clinical specimens as early as 1943. Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens. In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease. The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented. Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources. The mode of transmission from drinking water is unclear. The Legionellaceae are gram-negative, facultative, intracellular pathogens. The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth. Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear. Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection.

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Section: Microbiology and Immunologymentioning

confidence: 99%

Legionnaires disease: historical perspective

1988

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“…A correlation between catalase activity and virulence has been noted for several pathogenic bacterial species, including Staphylococcus aureus (4), Neisseria meningitidis (5), Legionella pneumophila (6), Nocardia asteroides (7), and Mycobacterium tuberculosis (8,9). However, these studies were conducted using naturally occurring strains, raising the possibility that additional virulence determinants other than catalase might have differed between isolates.…”

Section: Introductionmentioning

confidence: 99%

DNA repair is more important than catalase for Salmonella virulence in mice.

Buchmeier¹,

Libby²,

Xu³

et al. 1995

J. Clin. Invest.

138

102

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Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites such as hydrogen peroxide (H202), which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxify reactive oxygen species, and DNA repair systems which repair damage resulting from oxidative stress. To determine the relative importance of these two potentially protective defense mechanisms against oxidative stress encountered by Salmonella during infection of the host, a Salmonella typhimurium double mutant unable to produce either the HPI or HPII catalase was constructed, and compared with an isogenic recA mutant deficient in DNA repair. The recA mutant was hypersusceptible to H202 at low cell densities in vitro, while the catalase mutant was more susceptible to high H202 concentrations at high cell densities. The catalase mutant was found to be resistant to macrophages and retained full murine virulence, in contrast to the recA mutant which previously was shown to be macrophagesensitive and attenuated in mice. These observations suggest that Salmonella is subjected to low concentrations of H202 while at relatively low cell density during infection, conditions requiring an intact DNA repair system but not functional catalase activity. (J. Clin. Invest. 1995. 95:1047-1053

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“…In fact, no catalase activity has been detected in strain Patoc1, and strain Hardjoprajitno hydrolyzes only 16 mol of H 2 O 2 per min per 10 9 cells (2). This is likely to be the reason that leptospires show a higher susceptibility to H 2 O 2 toxicity than other bacteria such as Staphylococcus aureus (21), Legionella pneumophila (12), Listeria monocytogenes (4), and E. coli (19). That H 2 O 2 is less reactive than other products of oxygen metabolism such as O 2 Ϫ , OH, and hypohalous acid allows it to pass intact through cell membranes (8), diffuse within biological fluids containing little or no catalase, and act as an oxidizing agent (18).…”

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confidence: 99%

Leptospires Are Killed In Vitro by Both Oxygen-Dependent and -Independent Reactions

2002

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This study reports for the first time that leptospires are killed by H 2 O 2 and by low-molecular-weight primary granule components, which are agents normally released by neutrophils upon stimulation. Although both pathogenic and nonpathogenic strains were sensitive to H 2 O 2 -mediated killing, nonpathogenic organisms were found to be more susceptible. In addition, the killing of leptospires by H 2 O 2 was found to be independent of the presence of the neutrophil primary granule component myeloperoxidase and therefore not a consequence of halogenation reactions. We have also determined that leptospires are significantly sensitive only to primary granule components and, among those, to proteins and/or peptides of less than 30 kDa.Leptospires are the etiological agents of leptospirosis, a zooanthroponosis widespread throughout the world. The course of human leptospirosis ranges from mild to severe; some forms can be fatal, depending on the serovar of Leptospira involved and its virulence.Although we are far from having a complete picture of the Leptospira pathogenic factors, it is clear that these organisms are invasive and that the success of their invasions is mainly due to their ability to survive and grow in tissues by escaping natural defense mechanisms such as phagocytic cells, the complement system, and pharmacologically active tissue peptides and mediators. In fact, pathogenic leptospires can survive in the nonimmune host by evading complement-mediated killing (6) and (probably) phagocytosis. Studies have shown that pathogenic leptospires bind nonopsonically to and are slowly internalized by guinea pig macrophages and human polymorphonuclear leucocytes (1,(5)(6)(7)20). Although nonpathogenic spirochetes are rapidly engulfed and killed by human polymorphonuclear phagocytes, there is no clear evidence of the killing of pathogenic spirochetes other than that mediated by specific antibodies directed against some of their surface components (5). Moreover, live pathogenic leptospires can partially escape uptake by Kupffer cells from perfused rat liver (16). Overall, these data indicate that survival of leptospires is due primarily to scarce uptake by phagocytes. However, whether those leptospires that have been engulfed through nonopsonic phagocytosis are susceptible to intracellular killing is not known.The bactericidal systems activated after uptake by phagocytes include the generation of oxygen metabolites (O 2 -dependent killing) and the release of granule components such as proteins and peptides with microbicidal activity (10, 15) into the phagocytic vacuole (O 2 -independent killing) and combinations of the two. Since it is not known which among the killing mechanisms of phagocytes are effective toward leptospires, we have investigated the in vitro sensitivity of pathogenic and nonpathogenic strains of leptospires to the O 2 -dependent and -independent killing machinery of neutrophils.The oxygen-dependent chlorinating system constitutes an important microbicidal strategy employed by neutrophils (13), and ...

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The effect of oxygen-dependent antimicrobial systems on strains ofLegionella pneumophilaof different virulence

Cited by 21 publications

References 37 publications

Legionnaires disease: historical perspective

Legionnaires disease: historical perspective

DNA repair is more important than catalase for Salmonella virulence in mice.

Leptospires Are Killed In Vitro by Both Oxygen-Dependent and -Independent Reactions

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