Molecular Arms Race at the Host-Pathogen Interface

Reprogramming of Autophagy

Elucidating the enigmatic mechanisms through which pathogens exploit autophagy—a cellular self-digestion process. We have made groundbreaking discoveries, including identifying a pathogen effector that mimics a canonical motif—aka ATG8 interacting motif (AIM)—typically found in autophagy adaptors, to engage with ATG8/LC3 a key autophagy regulator conserved in plants and animals (Dagdas et al., 2016).

Building on this foundation, we unveiled a defense-related autophagy pathway, regulated by the autophagy receptor NBR1, targeting the pathogen interface (The extra-haustorial membrane) (Dagdas & Pandey et al., 2018).

More recently, our research has identified a defense-related secretory pathway and unveiled a strategy by which pathogens subvert this pathway by channelling it to the host autophagy machinery (Pandey et al., 2021).

Importantly, we’ve engineered an innovative molecular tool—a peptide derivative of the pathogen effector—that acts as a genetically encodable autophagy inhibitor (Pandey et al., 2021).

Remarkably, we have developed a high-throughput AI-guided computational pipeline for fast-forward discovery of new autophagy modulators, including those among pathogen effectors (Ibrahim et al., 2023).

NLR trafficking

Dynamic localization of NRC4 around P. infestans haustorium. During infection, the helper NLR NRC4 shifts its localization to accumulate at the extra-haustorial membrane (EHM) that envelopes the pathogen haustorium.

In the presence of the sensor NLR Rpiblb2, NRC4 gets activated and forms resistosome like puncta, representing its oligomeric state, that insert into the EHM (extra-haustorial membrane) and the plasma membrane (Duggan et al., 2021).

Our research have revealed that puncta formation is a general hallmark of activated helper NLRs (NRCs) (Contreras et al., 2023). Other studies also showed that activated NLRs form puncta that associate with the plasma membrane. This phenomenon is associated with the formation of membrane pores and calcium influx, leading to cell death (Jacob et al., 2021). We reason that these puncta are resistosomes or groups of membrane associated resistosomes.

Organelle and vesicle trafficking