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Such infections have been frequently reported worldwide and are currently gaining clinical research relevance owing to their resistant character, representing a bottleneck in treating affected people. Resistant fungi are an emergent public health threat. The upsurge of such pathogens has led to new research toward unraveling the destructive potential evoked by these species. Some fungi\u2014grouped into Candida, Aspergillus, and Cryptococcus\u2014are causative agents of severe and systemic infections. They are associated with high mortality rates and have recently been described as sources of coinfection in COVID-hospitalized patients. Despite the efforts to elucidate the challenges of colonization, dissemination, and infection severity, the immunopathogenesis of fungal diseases remains a pivotal characteristic in fungal burden elimination. The struggle between the host immune system and the physiological strategies of the fungi to maintain cellular viability is complex. In this brief review, we highlight the relevance of drug resistance phenotypes in fungi of clinical significance, taking into consideration their physiopathology and how the scientific community could orchestrate their efforts to avoid fungal infection dissemination and deaths.<\/jats:p>","DOI":"10.3390\/pathogens12020293","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:33:27Z","timestamp":1675996407000},"page":"293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Addressing Microbial Resistance Worldwide: Challenges over Controlling Life-Threatening Fungal Infections"],"prefix":"10.3390","volume":"12","author":[{"given":"Leonardo","family":"Martins-Santana","sequence":"first","affiliation":[{"name":"Department of Genetics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Patini","family":"Rezende","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1951-4741","authenticated-orcid":false,"given":"Antonio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-4276","authenticated-orcid":false,"given":"Nilce Maria","family":"Martinez-Rossi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-3698","authenticated-orcid":false,"given":"Fausto","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fmicb.2019.00214","article-title":"The Still Underestimated Problem of Fungal Diseases Worldwide","volume":"10","author":"Fausto","year":"2019","journal-title":"Front. 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