Long‐distance early endosome motility in Aspergillus fumigatus promotes normal hyphal growth behaviors in controlled microenvironments but is dispensable for virulence

In filamentous fungi, early endosomes are continuously trafficked to, and from, the growing hyphal tip by microtubule‐based motor proteins, serving as platforms for the long‐distance transport of diverse cargos including mRNA, signaling molecules, and other organelles which hitchhike on them. While the cellular machinery for early endosome motility in filamentous fungi is fairly well characterized, the broader physiological significance of this process remains less well understood. We set out to determine the importance of long‐distance early endosome trafficking in Aspergillus fumigatus, an opportunistic human pathogenic fungus that can cause devastating pulmonary infections in immunocompromised individuals. We first characterized normal early endosome motile behavior in A. fumigatus, then generated a mutant in which early endosome motility is severely perturbed through targeted deletion of the gene encoding for FtsA, one of a complex of proteins that links early endosomes to their motor proteins. Using a microfluidics‐based approach we show that contact‐induced hyphal branching behaviors are impaired in ΔftsA mutants, but that FtsA‐mediated early endosome motility is dispensable for virulence in an invertebrate infection model. Overall, our study provides new insight into early endosome motility in an important human pathogenic fungus. Synopsis Early endosomes are well‐known to undergo long‐distance microtubule‐dependent trafficking in filamentous fungi, but the physiological importance of this phenomenon remains largely unclear. Here, we demonstrate, through targeted disruption of the FtsA/HookA/FhipA motor‐cargo tethering complex, that dynein‐dependent early endosome motility is dispensable for pathogenesis by the human opportunistic pathogen Aspergillus fumigatus, but is required for normal contact‐mediated hyphal growth behaviors within controlled microenvironments.