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The big challenge of drug resistance! How does N. glabratus defeat the most common antifungal drugs?
In the 21st century, with medical advances and the increase in patients with immune system diseases, the yeast N. glabratus has gradually received more and more attention. N. glabratus was once known as Candida glabrata, and although its sexual reproductive cycle has not been documented to date, the presence of multiple pair-type strains makes it somewhat adaptable to the human commensal environment. This yeast is commonly found in human mucosal tissue, but in people with compromised immune systems, its role as an opportunistic pathogen becomes increasingly apparent, becoming the second or third most common cause of various infections.
Infections caused by N. glabratus can affect the genitourinary tract and even cause systemic infection (candidemia) by entering the bloodstream, especially in immunosuppressed patients. The clinical importance of this yeast is increasingly recognized, especially in hospital-acquired infections, not only because of its inherent high antifungal resistance but also because of its potential causative agent.
The inherent resistance of N. glabratus to antifungal drugs makes it a huge challenge in treatment, especially the increasing resistance to common triazole drugs.
Clinical relevance
The growth of N. glabratus in medical settings is closely related to its highly significant drug resistance, especially to triazoles. In addition to its inherent resistance to antifungal drugs, this yeast possesses a range of potential pathogenic factors. One of them is the expression of adhesion factors. These genes are mainly located in the sub-terminal regions of chromosomes and are highly activated by environmental signals, allowing them to adhere to biotic and abiotic surfaces.
The biofilm formation of N. glabratus makes it more resistant to antifungal drugs, which is why conventional antifungal treatments often fail when faced with this pathogen.
Diagnosis
For non-Candida vaginal infections, culture methods are considered an effective way to identify them, but urine tests are relatively less accurate. Although cultures take several days to proliferate, once the yeast is isolated, identification is relatively quick. Diagnosis of skin diseases is often difficult because culture results from swabs and biopsies may appear negative and require special testing. N. glabratus is listed in the "rare disease" database of the National Institutes of Health, and its pathogenicity compared with other Candida species has increasingly highlighted the problem of drug resistance.
Treatment options
A major phenotypic and potential pathogenic factor of N. glabratus is its low-level intrinsic resistance to common triazole antifungals. Even antifungal drugs like fluconazole and ketoconazole are only effective in treating N. glabratus in 15-20% of cases. Although it is relatively sensitive to polyene drugs (such as amphotericin B and flucytosine), the side effects of some drugs limit its clinical application. The first choice for treating vaginal infections may be a seven-day course of terconazole cream, but the efficacy is only about 40%, and recurrences are quite common.
Evolutionary relationship
N. glabratus has profound evolutionary connections with other yeasts. It is reported that it is more closely related to the yeast genus Saccharomyces cerevisiae, showing its biological similarity. However, the frequent recombination of the genome of N. glabratus gives it a stronger ability to survive in the face of stressful environments. Some scholars believe that this is related to its pathogenic potential.
After discussing the drug resistance and pathogenicity of N. glabratus, we should not only pay attention to its resistance to existing antifungal drugs, but also think about the deeper biological mechanisms and evolutionary processes.
In the face of the challenge of drug resistance in N. glabratus, the scientific community needs to continue exploration and research to find more effective solutions. In this competition for antifungal drugs, can we find an effective strategy against N. glabratus to protect the health and safety of patients?
