{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:23:02Z","timestamp":1789431782174,"version":"build-2803163510"},"reference-count":83,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,3,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida glabrata<\/jats:italic>\n                      is an opportunistic fungal pathogen that causes both superficial and systemic infections in humans, accounting for 15%\u201325% of invasive candidiasis cases. Macrophages play a crucial role in antifungal immunity by internalizing\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      ; however, the fungus has evolved strategies to survive and even proliferate within phagosomes. It has been suggested that\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      may utilize its life within macrophages to evade immune detection and disseminate throughout the body. We observed that, compared to fungi like\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      only slowly escapes from macrophages, with host cells bursting after 2\u20133 days. This delay is fungal-driven rather than host-induced and is not solely due to replication in the yeast form\n                      <jats:italic toggle=\"yes\">per se<\/jats:italic>\n                      . We identified protein kinases involved in exit timing, especially the Ksp1 kinase, the deletion of which accelerates macrophage cell lysis. Its loss increases mitophagy and the formation of\n                      <jats:italic toggle=\"yes\">petites,<\/jats:italic>\n                      a respiration-deficient phenotype associated with resistance toward antifungals and, more importantly, to phagocytic killing. Moreover, deletion of\n                      <jats:italic toggle=\"yes\">KSP1<\/jats:italic>\n                      enhances resistance to multiple antifungals, suggesting that this kinase may be at the core of a broader cross-adaptive survival strategy by\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      . Collectively, our findings indicate that\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      may actively prolong its intramacrophagal phase, which could contribute to immune evasion, antifungal resistance, and potential recurrence of infection. Moreover, these results reinforce the notion of a critical role of\n                      <jats:italic toggle=\"yes\">petite<\/jats:italic>\n                      formation in persistent and recurrent infections. They also show the need to adapt clinical diagnostics and therapy to detect and manage these respiration-deficient variants.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Candida glabrata<\/jats:italic>\n                        is a major cause of invasive candidiasis and is difficult to treat due to its intrinsic resistance to antifungal drugs and its ability to survive inside host immune cells. How this pathogen regulates its intracellular lifestyle and exit from macrophages remains poorly understood. We show that\n                        <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                        actively modulates its interaction with macrophages through the protein kinase Ksp1, which regulates mitochondrial dysfunction and the formation of respiration-deficient cells. These variants display enhanced resistance to two antifungal drugs and killing by phagocytes. Our findings suggest that prolonging the intramacrophage phase and generating stress-resistant variants are key components of\n                        <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                        \u2019s survival strategy. Recognizing these processes has important implications for clinical diagnostics and the management of persistent and recurrent fungal infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03885-25","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:01:10Z","timestamp":1771596070000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["\u201cShould I stay or should I go\u201d\u2014a kinase delays escape of\n                    <i>Candida glabrata<\/i>\n                    from macrophages"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7932-8757","authenticated-orcid":false,"given":"Theresa","family":"Lange","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055s37c97","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of 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