Hyaluronidase from infective Ancylostoma hookworm larvae and its possible function as a virulence factor in tissue invasion and in cutaneous larva migrans

Abstract

During skin penetration, infective hookworm larvae encounter hyaluronic acid as they migrate between epidermal keratinocytes and through the ground substance of the dermis. A hyaluronidase would facilitate passage through the epidermis and dermis during larval invasion. Zoonotic hookworm larvae of the genus Ancylostoma were shown to contain a hyaluronidase activity that migrated on modified sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) hyaluronic acid gels with an apparent Mr of 49,000. A second form with an M, of 87,000 was also identified. The major etiologic agent of cutaneous larva migrans, A. braziliense, was shown to have the greatest enzyme activity, hydrolyzing up to 3.3 Kg of hyaluronic acid per h per ,ug of total parasite protein at pH 6.0, whereas A. caninum and A. tubaeforme each had much less enzyme activity. The differences in enzyme activities between species correlated with differences in the intensities of the lytic zones at 49 and 87 kDa on SDS-PAGE hyaluronic acid gels. Hookworm hyaluronidase activity exhibited a broad pH optimum between 6.0 and 8.0 and did not hydrolyze chondroitin sulfate, two features that suggest that the hookworm enzyme is more like the invertebrate leech hyaluronidase than mammalian testicular or lysosomal hyaluronidase. Larvae of A. braziliense were shown to release hyaluronidase activity and degrade radiolabeled hyaluronic acid in vitro. Gold sodium thiomalate was identified as an enzyme inhibitor. The hyaluronidase is the second major virulence factor that we have identified from infective hookworm larvae. * Corresponding author. sively in the basal layer of the epidermis to cause cutaneous larva migrans (7, 27-29).

Determining the occurrence of the Uncinaria stenocephala and Ancylostoma caninum nematode invasion in dogs in Poland, with special emphasis on the Lublin region

“…W tym przypadku larwy docierają do gruczołów Liberkühna w dwunastnicy i dojrzewają płciowo, prowadząc do podostrego lub chronicznego nieżytowego zapalenia jelita (2,18,54). Natomiast larwy A. caninum mogą także penetrować do głębiej położonych błon jelita oraz innych narządów, a z powodu silnej aktywności proteolitycznej dominuje tu droga zarażenia per cutis (2,15,31,62). Po pokonaniu bariery skórnej larwy docierają do żylnych lub limfatycznych naczyń włosowatych i przemieszczają się do serca, a następnie drogą krążenia do płuc i drogą drzewa oskrzelowego do tchawicy i krtani.…”

Cutaneous larva migrans: clinical features and management of 44 cases presenting in the returning traveller

“…The larvae hatch from the eggs and are able to penetrate the human epidermis and less often into the upper dermis, possibly mediated by the production and secretion of hyaluronidase. 1 The larvae are not able to complete their life cycle within humans and die after weeks or months. The typical clinical picture is characterized by an erythematous linear or serpiginous tract, which is intensely itchy and may enlarge by a few centimetres each day.…”

Very High‐ and High‐Frequency Ultrasound Features of Cutaneous Larva Migrans

“…Then, the larvae presumably die because they lack collagenase, which is an enzyme needed to disrupt this basement membrane in human hosts . However, it has been reported that larvae can penetrate the dermis and lymphatic channels in their natural hosts because of the generation of hyaluronidase . Moreover, histologic evidence of larva specimens in deeper layers has been previously described in the literature, which has shown these parasites within the human sebaceous glands of the scalp and the follicular regions …”