TY - JOUR
T1 - Too much of a good thing
T2 - Overproduction of virulence factors impairs cryptococcal pathogenicity
AU - Reuwsaat, Julia C.V.
AU - Doering, Tamara L.
AU - Kmetzsch, Livia
N1 - Funding Information:
During the period of data collection JCVR was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil) and the Advanced Network of Computational Biology - RABICÓ - Biocomputational Grant 23038.010041/2013-13; she is now supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil ? Grant 150414/2020-0). The experiments summarized here were largely supported by National Institutes of Health grants AI087794 and AI140979 to TLD and grants from CAPES, CNPq (310510/2018-0), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil) to LK. We thank Liza Loza for helpful comments on the manuscript and Heryk Motta for contributions to Figure 2.
Publisher Copyright:
© 2021 Shared Science Publishers OG. All rights reserved.
PY - 2021
Y1 - 2021
N2 - The regulation of virulence factor production and deployment is crucial for the establishment of microbial infection and subsequent pathogenesis. If these processes are not properly coordinated, the infecting pathogen is less likely to both survive the immune response and cause damage to the host. One key virulence factor of the opportunistic fungal pathogen Cryptococcus neoformans, which kills almost 200,000 people each year worldwide, is a polysaccharide capsule that surrounds the cell wall; this structure helps the fungal cells resist engulfment and elimination by host phagocytes. Another important virulence trait is the development of a giant (Titan) cell morphotype that increases fungal resistance to phagocytosis, oxidative stress, and antifungal treatment. We recently identified the transcription factor Pdr802 as essential for C. neoformans adaptation to and survival under host conditions both in vitro and in vivo (Reuwsaat et al., mBio, doi: 10.1128/mBio.03457-20). Cryptococci lacking Pdr802 display enlarged capsules and enhanced Titan cell production, along with dramatically reduced virulence in a mouse model of infection. These results demonstrate that more is not necessarily better when it comes to virulence factors. Instead, precise regulation of these traits, to avoid both under- and overexpression, is critical for the success of this pathogen as it faces the challenges imposed by the host environment.
AB - The regulation of virulence factor production and deployment is crucial for the establishment of microbial infection and subsequent pathogenesis. If these processes are not properly coordinated, the infecting pathogen is less likely to both survive the immune response and cause damage to the host. One key virulence factor of the opportunistic fungal pathogen Cryptococcus neoformans, which kills almost 200,000 people each year worldwide, is a polysaccharide capsule that surrounds the cell wall; this structure helps the fungal cells resist engulfment and elimination by host phagocytes. Another important virulence trait is the development of a giant (Titan) cell morphotype that increases fungal resistance to phagocytosis, oxidative stress, and antifungal treatment. We recently identified the transcription factor Pdr802 as essential for C. neoformans adaptation to and survival under host conditions both in vitro and in vivo (Reuwsaat et al., mBio, doi: 10.1128/mBio.03457-20). Cryptococci lacking Pdr802 display enlarged capsules and enhanced Titan cell production, along with dramatically reduced virulence in a mouse model of infection. These results demonstrate that more is not necessarily better when it comes to virulence factors. Instead, precise regulation of these traits, to avoid both under- and overexpression, is critical for the success of this pathogen as it faces the challenges imposed by the host environment.
KW - Capsule
KW - Cryptococcus neoformans
KW - Fungal pathogenesis
KW - Pdr802
KW - Titan cells
KW - Virulence factors
UR - http://www.scopus.com/inward/record.url?scp=85106370506&partnerID=8YFLogxK
U2 - 10.15698/MIC2021.05.750
DO - 10.15698/MIC2021.05.750
M3 - Review article
AN - SCOPUS:85106370506
SN - 2311-2638
VL - 8
SP - 108
EP - 110
JO - Microbial Cell
JF - Microbial Cell
IS - 6
ER -