Aquarium-Borne Mycobacterium marinum Skin Infection

Huminer, David; Pitlik, Silvio; Block, Colin; Kaufman, Lea; Amit, Sami; Rosenfeld, Joseph B.

doi:10.1001/archderm.1986.01660180104026

Cited by 114 publications

(69 citation statements)

References 41 publications

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“…M. marinum granulomas in the frog share many features with human tuberculous ones, such as mature macrophages, epithelioid cells, and extracellular matrix components, yet lack caseation and giant cells. While M. marinum can cause caseous necrosis in humans, goldfish, and the toads Xenopus laevis and Xenopus borealis (9,28,57,58), this does not appear to be a feature of R. pipiens granulomas. This is likely due to differences in the host response to infection-many frog species fail to undergo caseation, a phenomenon for which a pathological basis is not clear (7).…”

Section: Discussionmentioning

confidence: 99%

Dynamic Nature of Host-Pathogen Interactions inMycobacterium marinumGranulomas

Bouley¹,

Ghori

Mercer³

et al. 2001

Infect Immun

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Mycobacterium marinum causes long-term subclinical granulomatous infection in immunocompetent leopard frogs (Rana pipiens). These granulomas, organized collections of activated macrophages, share many morphological features with persistent human tuberculous infection. We examined organs of frogs with chronic M. marinum infection using transmission electron microscopy in conjunction with immunohistochemistry and acid phosphatase cytochemistry to better define the bacterium-host interplay during persistent infection. Bacteria were always found within macrophage phagosomes. These phagosomes were often fused to lysosomes, in sharp contrast to those formed during in vitro infection of J774 macrophage-like cells by M. marinum. The infected macrophages in frog granulomas showed various levels of activation, as evidenced by morphological changes, including epithelioid transformation, recent phagocytic events, phagolysosomal fusion, and disintegration of bacteria. Our results demonstrate that even long-term granulomas are dynamic environments with regard to the level of host cell activation and bacterial turnover and suggest a continuum between constantly replicating bacteria and phagocytic killing that maintains relatively constant bacterial numbers despite an established immune response. Infection with a mutant bacterial strain with a reduced capacity for intracellular replication shifted the balance, leading to a greatly reduced bacterial burden and inflammatory foci that differed from typical granulomas.

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Section: Discussionmentioning

confidence: 99%

Dynamic Nature of Host-Pathogen Interactions inMycobacterium marinumGranulomas

Bouley¹,

Ghori

Mercer³

et al. 2001

Infect Immun

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“…Mycobacterium marinum causes primarily skin lesions on the extremities in humans (24,27). This is most likely due to its low temperature for optimal growth of between 25 and 35°C (9), since human skin temperatures are thought to be in the range of 33 to 35°C (43), which is similar to the case for another mycobacterial skin pathogen, Mycobacterium leprae (11).…”

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AMycobacterium marinum mel2Mutant Is Defective for Growth in Macrophages That Produce Reactive Oxygen and Reactive Nitrogen Species

et al. 2007

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Macrophages produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) in response to bacterial infections. Mycobacteria are relatively resistant to ROS, but RNS inhibit growth of, and possibly even kill, mycobacteria in activated macrophages. We recently constructed a Mycobacterium marinum mel2 locus mutant, which is known to affect macrophage infection. We found previously that the mel2 locus confers resistance to ROS and RNS in laboratory medium, suggesting that this locus might play a similar role during growth in macrophages. Since J774A.1 murine macrophages produce high levels of ROS and RNS upon activation with gamma interferon (IFN-␥), we examined the effects of IFN-␥ on ROS and RNS production by these cells as well as the effects on growth of M. marinum in these cells. We found that an M. marinum mutant with mutation of the first gene in the mel2 locus, melF, is defective for growth in IFN-␥-plus-lipopolysaccharidetreated J774A.1 cells and that this defect is abrogated by the presence of either inhibitors of nitric oxide synthase or ROS scavengers. Furthermore, the M. marinum melF mutant displays a defect at late stages in the mouse footpad model of infection. These phenotypic characteristics could be complemented fully by the entire mel2 locus but only partially by the presence of melF alone, supporting data suggesting that this insertion mutation has polar effects on downstream genes in the mel2 locus. These observations demonstrate that the M. marinum mel2 locus plays a role in resistance to ROS and RNS produced by activated macrophages.More than 150 Mycobacterium marinum infections are observed in humans each year (16), usually associated with aquatic sports, fishing, or aquarium maintenance. Mycobacterium marinum causes primarily skin lesions on the extremities in humans (24,27). This is most likely due to its low temperature for optimal growth of between 25 and 35°C (9), since human skin temperatures are thought to be in the range of 33 to 35°C (43), which is similar to the case for another mycobacterial skin pathogen, Mycobacterium leprae (11). During skin infections in humans (12) and mice (9, 13), M. marinum replicates within macrophages, and disease is characterized by granuloma formation, with some similarities to those in human tuberculosis (12,22). Macrophages from numerous species (4, 21, 33, 40) and epithelial cell lines (44, 45) can be efficiently infected by and allow growth of M. marinum. Thus, M. marinum, similar to other pathogenic mycobacteria, can resist or avoid the bactericidal mechanisms of macrophages.Mycobacteria are relatively resistant to the reactive oxygen species (ROS) produced by macrophages (8), but their intracellular growth is inhibited by activation with gamma interferon (IFN-␥) through the production of reactive nitrogen species (RNS) by nitric oxide synthase (7,18,31). Furthermore, mice that are respiratory burst deficient as a result of a defect in NADPH oxidase, similar to chronic granulomatous disease patients, whose macrophages do not produce sig...

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“…M. marinum causes infections in humans and in fish (7,31). Large outbreaks of infection due to M. marinum have been described in association with swimming pools (swimming pool granuloma) (42) and fish tanks (fish tank granuloma) (13,14,17,19). M. ulcerans and M. marinum, once cultured, are readily identified by conventional mycobacterial characterization methods (46).…”

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GenotypingMycobacterium ulceransandMycobacterium marinumby Using Mycobacterial Interspersed Repetitive Units

et al. 2005

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A novel category of variable tandem repeats (VNTR) called mycobacterial interspersed repetitive units (MIRUs) has been identified for Mycobacterium ulcerans (n ‫؍‬ 39), M. marinum (n ‫؍‬ 27), and one related organism. Fifteen MIRU loci were identified in the genome of M. marinum and were used to genotype M. ulcerans, M. marinum, and an M. marinum-like organism that is considered a possible missing link between M. marinum and M. ulcerans. Seven MIRU loci were polymorphic, and locus-specific PCRs for four of these loci differentiated seven M. ulcerans genotypes, four M. marinum genotypes, and a unique genotype for the missing link organism. The seven M. ulcerans genotypes were related to six different geographic origins of isolates. All isolates from West and Central Africa, including old and recent isolates, belonged to the same genotype, emphasizing the great spatiotemporal homogeneity among African isolates. Unlike the M. ulcerans genotypes, the four M. marinum genotypes could not be clearly related to the geographic origins of the isolates. According to MIRU-VNTR typing, all M. ulcerans and M. marinum isolates of American origin were closely related, suggesting a common American ancestor for these two pathogenic species on the American continents. MIRU typing has significant potential value for discriminating between reoccurrence and reinfection for M. ulcerans disease.Mycobacterium ulcerans causes Buruli ulcer (BU), a disease that represents, after tuberculosis and leprosy, the third most common mycobacterial disease in humans (23,27). BU has been observed in many tropical areas, but most patients have come from Central and West Africa and Australia (5,11,27). Epidemiologically, the disease is associated with riverine and swampy terrains (27). BU is a devastating disease characterized by necrotizing, ulcerative lesions of subcutaneous tissues and the overlying skin. The main specific genomic characteristics of M. ulcerans are the IS2404 element (34) and a 174-kb plasmid(s) that houses the genes for mycolactone, a polyketide toxin (39). M. marinum causes infections in humans and in fish (7,31). Large outbreaks of infection due to M. marinum have been described in association with swimming pools (swimming pool granuloma) (42) and fish tanks (fish tank granuloma) (13,14,17,19). M. ulcerans and M. marinum, once cultured, are readily identified by conventional mycobacterial characterization methods (46). Various DNA-based techniques have been used to type mycobacteria (6,33,35). Such studies have demonstrated a close taxonomic relationship between M. ulcerans and M. marinum, although M. ulcerans harbors IS2404 and M. marinum does not (34). Recently, however, IS2404 was found in an unusual mycobacterial isolate with phenotypic properties closely related to those of M. marinum (4).Previous studies showed limited genotypic diversity in M. ulcerans, especially among isolates from a given geographic region. PCR-restriction profile analyses of 16S rRNAs showed four different genotypic profiles of M. ulcerans, i.e., the ...

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Aquarium-Borne Mycobacterium marinum Skin Infection

Cited by 114 publications

References 41 publications

Dynamic Nature of Host-Pathogen Interactions inMycobacterium marinumGranulomas

Dynamic Nature of Host-Pathogen Interactions inMycobacterium marinumGranulomas

AMycobacterium marinum mel2Mutant Is Defective for Growth in Macrophages That Produce Reactive Oxygen and Reactive Nitrogen Species

GenotypingMycobacterium ulceransandMycobacterium marinumby Using Mycobacterial Interspersed Repetitive Units

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