Studies on a Certain Spreading Factor Existing in Bacteria and Its Significance for Bacterial Invasiveness

Duran-Reynals, F.

doi:10.1084/jem.58.2.161

Cited by 139 publications

(45 citation statements)

References 8 publications

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“…Consistent with this view, S. aureus hysA mutants exhibit a hypovirulent phenotype in models of acute pulmonary and cutaneous infection (22,23). In addition, hyaluronidases from numerous Gram-positive pathogens have been shown to promote tissue penetrance of bacteria, toxins, and large-molecular-mass dyes in the vicinity of the challenge site (25,57). In the present study, we employed a medical device-associated infection model to show that S. aureus-derived HysA is an important virulence factor within the context of chronic biofilm infection.…”

Section: Discussionmentioning

confidence: 82%

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

et al. 2016

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Staphylococcus aureus is a leading cause of chronic biofilm infections. Hyaluronic acid (HA) is a large glycosaminoglycan abundant in mammalian tissues that has been shown to enhance biofilm formation in multiple Gram-positive pathogens. We observed that HA accumulated in an S. aureus biofilm infection using a murine implant-associated infection model and that HA levels increased in a mutant strain lacking hyaluronidase (HysA). S. aureus secretes HysA in order to cleave HA during infection. Through in vitro biofilm studies with HA, the hysA mutant was found to accumulate increased biofilm biomass compared to the wild type, and confocal microscopy showed that HA is incorporated into the biofilm matrix. Exogenous addition of purified HysA enzyme dispersed HA-containing biofilms, while catalytically inactive enzyme had no impact. Additionally, induction of hysA expression prevented biofilm formation and also dispersed an established biofilm in the presence of HA. These observations were corroborated in the implant model, where there was decreased dissemination from an hysA mutant biofilm infection compared to the S. aureus wild type. Histopathology demonstrated that infection with an hysA mutant caused significantly reduced distribution of tissue inflammation compared to wild-type infection. To extend these studies, the impact of HA and S. aureus HysA on biofilm-like aggregates found in joint infections was examined. We found that HA contributes to the formation of synovial fluid aggregates, and HysA can disrupt aggregate formation. Taken together, these studies demonstrate that HA is a relevant component of the S. aureus biofilm matrix and HysA is important for dissemination from a biofilm infection.

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Section: Discussionmentioning

confidence: 82%

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

et al. 2016

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“…Duran-Reynals (1933) observed that culture extracts of S. aureus increased permeability of rabbit tissue to vaccinia virus, toxins and dyes. Subsequently, the 'spreading factor' was identified as a HL (Linker et al, 1955).…”

Section: Introductionmentioning

confidence: 99%

The hyaluronate lyase of Staphylococcus aureus – a virulence factor?

et al. 2004

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The hyaluronate lyase (HL) gene of Staphylococcus aureus 8325-4 (hysA) was inactivated in vitro with the insertion of the erythromycin determinant, ermC, from plasmid pE194. The hysA : : ermC mutation was introduced into S. aureus via a temperature-sensitive shuttle vector, where it underwent homologous recombination with the wild-type (w.t.) allele. The insertion of ermC in the chromosomal hysA locus was confirmed by Southern blot hybridization and the loss of HL activity was demonstrated macroscopically by a plate assay. The importance of HL for pathogenicity was assessed by comparing the virulence of the HL " mutant strain to that of the w.t. in an established mouse abscess model of S. aureus infection. A significantly higher cell recovery was obtained from lesions infected with the w.t. strain compared to the lesions infected with the HL " strain (P =0?01). Although the lesion areas from both groups were not significantly different (P=0?9) they were of different morphology. A colorimetric assay was used to measure HL activity from culture supernatants of the S. aureus 8325-4 strains w.t., WA250 (agr) and PC1839 (sar) grown in a chemically defined medium. HL activity reached a maximum in the w.t. strain during mid-exponential phase (t=5 h) and while it showed a 16-fold decrease in the agr mutant it increased 35-fold in the sar mutant background. These results strongly suggest that HL is a virulence factor which is important in the early stages of subcutaneous infections.

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“…Both of these strains of streptococcus contain the specific carbohydrate and are very active producers of the spreading factor. 2 years ago from an abscess in man. Both are very active in production of the spreading factor.…”

Section: Pneumococcus R Variant--this Was the Strain 1/192/r Obtaimentioning

confidence: 99%

The Extent of Local Dispersion of Infectious Agents as a Factor in Resistance to Infection

Duran-Reynals

1935

Journal of Experimental Medicine

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The reactions of the host to bacterial and virus infections have been measured in terms of the minimal lethal dose for different sites of inoculations, and they have been appraised in terms of damage to tissues and in terms of tissue specificity; but the extent of dispersion of the infective agents as affecting the results has in the past been accorded little attention. In recent work from this laboratory a chemical fraction which causes dispersion of particulate matter injected with it into the skin and extracts from testicle (1) and from invasive bacteria (2), which have the same effect, served as a tool to show that the extent of dispersion of the infectious agent importantly influences the size of the lesions due to infection. It was found that intracutaneous inoculations into rabbits of testicle extract together with concentrated suspensions of bacteria resulted in more widespread lesions than inoculations of equally concentrated suspensions of bacteria in isotonic saline (3). It was later observed that inoculations of testicle extract with dilute suspensions of staphylococcus either produced lesions which were less widespread than those produced by saline suspensions or failed to produce a lesion (4). These results led to the supposition that in the case of bacteria there could be determined a critical concentration, the minimal effective concentration per unit area of infection, below which no reaction would occur, and above which the intensity of the reaction would be roughly proportional to the concentration. The critical concentration is presumably the resultant of local resistance of the host tissues, and of local virulence of the bacteria.

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Studies on a Certain Spreading Factor Existing in Bacteria and Its Significance for Bacterial Invasiveness

Cited by 139 publications

References 8 publications

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

The hyaluronate lyase of Staphylococcus aureus – a virulence factor?

The Extent of Local Dispersion of Infectious Agents as a Factor in Resistance to Infection

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