Reshuffling of Aspergillus fumigatus cell wall components chitin and ß-glucan under the influence of caspofungin or nikkomycin Z alone or in combination.

Chitin and ß-glucan are major cell wall components of Aspergillus spp. We investigated the antifungal activity of chitin synthesis inhibitors nikkomycin Z, polyoxin D, flufenoxuron, lufenuron, and teflubenzuron, alone and combined with the ß-glucan synthesis inhibitor caspofungin. Only nikkomycin Z and caspofungin were found to act synergistically. The nikkomycin Z-induced chitin decrease corresponded with a ß-glucan increase, while with the caspofungin-induced ß-glucan decrease, an increase in chitin was found. This could explain the synergistic activity of this combination of drugs.

[A body packer with cannabis]. / Een bodypacker met cannabis.

BACKGROUND: In recent years, numerous reports have been published on body packers, i.e. people who use their own body to transport drugs. Most body packers swallow small packages of cocaine or heroin. CASE DESCRIPTION: We describe the case of a patient who, two days after ingestion of packages containing cannabis, was admitted for dizziness and drowsiness. Urinalysis was positive for cannabis and negative for other drugs. The deterioration in clinical status possibly indicated a burst package. The packages were surgically removed and the patient made a full recovery. CONCLUSION: Some body packers transport other drugs than cocaine or heroin, such as cannabis. In body packers who ingest cannabis, depressed consciousness is a main symptom of intoxication. They should be admitted and monitored for symptoms of intoxication or paralytic ileus. Laboratory tests provide qualitative support when interpreting clinical symptoms. Surgical intervention is indicated in cases of bowel obstruction or when intoxication due to package leakage is suspected.

A Polymorphism in the Chitotriosidase Gene Associated with Risk of Mycetoma Due to Madurella mycetomatis Mycetoma--A Retrospective Study.

BACKGROUND: Madurella mycetomatis is the most prevalent causative agent of eumycetoma in Sudan, an infection characterized by the formation of grains. Many patients are exposed to the causative agent, however only a small number develop infection. M. mycetomatis contains chitin in its cell wall, which can trigger the human immune system. Polymorphisms in the genes encoding for the chitin-degrading enzymes chitotriosidase and AMCase were described, resulting in altered chitinase activity. We investigated the association between 4 of these polymorphisms and the incidence of M. mycetomatis mycetoma in a Sudanese population. METHODOLOGY: Polymorphisms studied in 112 eumycetoma patients and 103 matched controls included a 24-bp insertion in the chitotriosidase gene (rs3831317), resulting in impaired chitinase activity and single nucleotide polymorphism (SNP) in the AMCase gene (rs61756687), resulting in decreased AMCase activity. Also, a SNP (rs41282492) and a 10-bp insertion in the 5'UTR region of the AMCase gene (rs143789088) were studied, both resulting in increased AMCase activity. DNA was isolated from blood and genotypes were determined using PCR-RFLP. PRINCIPAL FINDINGS: Histological staining proved the presence of chitin in the fungal grain. The polymorphism resulting in decreased chitotriosidase activity was associated with increased odds of eumycetoma (odds ratio 2.9; p = 0.004). No association was found for the polymorphisms in the genes for AMCase (all p>0.05). CONCLUSION: Decreased chitotriosidase activity was associated with increased risk of M. mycetomatis mycetoma.

Evidence supporting a role for mammalian chitinases in efficacy of caspofungin against experimental aspergillosis in immunocompromised rats.

OBJECTIVES: Caspofungin, currently used as salvage therapy for invasive pulmonary aspergillosis (IPA), strangely only causes morphological changes in fungal growth in vitro but does not inhibit the growth. In vivo it has good efficacy. Therefore the question arises how this in vivo activity is reached. Caspofungin is known to increase the amount of chitin in the fungal cell wall. Mammals produce two chitinases, chitotriosidase and AMCase, which can hydrolyse chitin. We hypothesized that the mammalian chitinases play a role in the in vivo efficacy of caspofungin. METHODS: In order to determine the role of chitotriosidase and AMCase in IPA, both chitinases were measured in rats which did or did not receive caspofungin treatment. In order to understand the role of each chitinase in the breakdown of the caspofungin-exposed cells, we also exposed caspofungin treated fungi to recombinant enzymes in vitro. RESULTS: IPA in immunocompromised rats caused a dramatic increase in chitinase activity. This increase in chitinase activity was still noted when rats were treated with caspofungin. In vitro, it was demonstrated that the action of both chitinases were needed to lyse the fungal cell wall upon caspofungin exposure. CONCLUSION: Caspofungin seemed to alter the cell wall in such a way that the two chitinases, when combined, could lyse the fungal cell wall and assisted in clearing the fungal pathogen. We also found that both chitinases combined had a direct effect on the fungus in vitro.