Relationship between the Antifungal Susceptibility Profile and the Production of Virulence-Related Hydrolytic Enzymes in Brazilian Clinical Strains ofCandida glabrata

Abstract

Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C. glabrata. All C. glabrata strains were susceptible to flucytosine. However, some of these strains showed resistance to amphotericin B (9.9%), fluconazole (15.4%), itraconazole (5.5%), or micafungin (15.4%). Overall, C. glabrata strains were good producers of catalase, aspartic protease, esterase, phytase, and hemolysin. However, caseinase and phospholipase in vitro activities were not detected. Statistically significant correlations were identified between micafungin minimum inhibitory concentration (MIC) and esterase production, between fluconazole and micafungin MIC and hemolytic activity, and between amphotericin B MIC and phytase production. These results contribute to clarify some of the C. glabrata mechanisms of pathogenicity. Moreover, the association between some virulence attributes and the regulation of antifungal resistance encourage the development of new therapeutic strategies involving virulence mechanisms as potential targets for effective antifungal drug development for the treatment of C. glabrata infections.

Virulence Attributes of Clinical Candida glabrata (Sensu Stricto) Isolates in the West Region of Cameroon

“…This result is very close to the results obtained in our study, as 37.04% of our isolates displayed a positive phospholipase activity. On the other hand, our results for phospholipase and protease activities differ from those obtained by Figueiredo-Carvalho et al [19] in Brazil, who detected phospholipase and protease activities in 0% and 95.6% (87) of strains respectively, among 91 C. glabrata strains isolated from a great diversity of samples including stool, urine, cervico-vaginal and oropharyngeal swabs. It was interesting to notice that 41.17% of the high producers of phospholipase (Pz < 0.7) in our study originated from the oro-pharyngeal swabs of diabetic patients and pregnant women.…”

“…No (0%) esterase activity was detected among our isolates, contrary to the positive esterase activity detected in 56.0% of C. glabrata sensu stricto strains in a study conducted by Figueiredo-Carvalho et al [19]. Results for esterase activity in our study concord with those of a study in Turkey which revealed that only one strain out of 14 C. glabrata sensu stricto strains isolated from bloodstream infection, had a positive esterase activity [19].…”

In Vitro Determination of Hydrolytic Enzymes and Echinocandin Susceptibility in Mexican Clinical Isolates of Candida glabrata Sensu Stricto

“…Thus, this putative virulence factor enables pathogen survival and persistence in the host (37). In the present study only five isolates were unable to produce HM, these findings are in agreement with previous publications (27,32,33), reflecting the importance of this key virulence attribute for C. glabrata. In fact, the hemolytic activity has been demonstrated as necessary for virulence in this yeast (38).…”

“…In the present study, the researchers found that all strains showed proteolytic activity, with an elevated percentage of isolates with very strong activity of AP (97.2%). As depicted in Table 2 dida spp., possibly through damage to the host cell membrane by digestion of lipids, facilitating tissue invasion as well as nutrient acquisition (35) In this work, the researchers detected 84 isolates (78.5%) with PP activity at different production levels, with these observations agreeing closely with certain studies (26,29) and more distantly with some additional reports (21,31); as opposed, other authors did not find PP activity (23,24,27,28,30,32), even in collections of numerous strains of C. glabrata (33). Otherwise, as expected, a limited number of isolates (12.1%) exhibited ES activity, agreeing with some studies (20,28,30,31) and in contrast to the work of Figueiredo-Carvalho et al (33), who reported an incidence of 56%, and further suggested that the production of this enzyme may vary according to the clinical source or the geographic region, from which the strains were iso-lated.…”

Molecular Epidemiology, Antifungal Susceptibility, and Virulence Evaluation of Candida Isolates Causing Invasive Infection in a Tertiary Care Teaching Hospital

“…Several virulence factors in Candida species are indispensable for their ability to cause disease, and these include extracellular hydrolytic enzymes, particularly proteases, phospholipases, and hemolysins, which facilitate food acquisition, adherence, colonization, invasion, diffusion, and escape from host immune responses ( Abbes et al., 2017 ; Figueiredo-Carvalho et al., 2017 ). Accurate identification of putative virulence factors in Candida spp.…”