Context: Late blight caused by Phytophthora infestans remains the most damaging potato disease. While single-site fungicides often lose efficacy due to target-site mutations, multi-site (non-specific) fungicides like mancozeb have long been considered more durable because they disrupt multiple biochemical targets at once. A new experimental-evolution study directly observes how resistance to a multi-site fungicide can emerge and then recede under changing selection pressure—offering rare, data-driven guidance for resistance management.

Study Design (in brief)

• Pathogen material: 10 distinct P. infestans genotypes combined into 98 populations with varying genetic complexity (1–10 genotypes per population).
• Selection regime: Continuous exposure on media with different mancozeb doses for 200 days (“acclimation”), followed by 200 days without mancozeb (“reversal”). Total observation window = 400 days.
• Measurements: Changes in resistance were quantified via colony growth; fitness costs were assessed through aggressiveness; and RNA-seq compared resistant vs sensitive isolates (± mancozeb) to map pathways involved.

Key Findings

• Resistance can arise to a multi-site fungicide: Populations developed measurable mancozeb resistance within ~200 days of continuous exposure.
• Reversibility after selection is removed: When mancozeb was withdrawn, resistance declined over the next ~200 days. Gains during acclimation and losses during reversal were approximately symmetrical, indicating a reversible phenotype over this timeframe.
• Mechanistic signals—efflux & endocytosis: Transcriptomics implicated ABC transporters (membrane efflux) and endocytosis-linked pathways in resistance development, consistent with non-target-site mechanisms for multi-site fungicides.
• Genetic diversity accelerates adaptation: Higher genotype complexity (i.e., more diverse populations) accelerated resistance evolution compared with simpler populations.
• Dose matters: Adequate/high doses inhibited resistance evolution relative to lower doses—likely by reducing population sizes and/or imposing stronger fitness penalties on resistant phenotypes.
• Trade-offs exist: Resistant isolates showed fitness costs (e.g., reduced aggressiveness). On removal of mancozeb, populations appeared to recover aggressiveness while shedding resistance, aligning with classic resistance-cost dynamics.
• Dose independence of resistance level: Once established, resistance expressed in one dose environment tended to generalize across doses, which aligns with broad efflux-based mechanisms.

What This Means for Field Management (evidence-led)

• Use label-appropriate doses: Sustained low-dose exposure favors selection; adequate dosing reduces the chance that partially tolerant subpopulations persist and adapt.
• Rotation & mixtures remain essential: Combine multi-site fungicides with single-site modes of action judiciously; avoid repeated selection in the same direction.
• “Drug holidays” may be viable—case by case: The observed reversibility suggests that re-introducing a multi-site after a sufficiently long break could restore efficacy. The exact pause length is pathogen- and chemistry-specific; field validation is required.
• Monitor population diversity: Regions or seasons with higher genotype diversity may require more conservative resistance-management (tighter rotations, fewer consecutive sprays with the same MoA).
• Track non-target-site markers: ABC transporter expression signatures and endocytosis-related responses merit exploration as molecular indicators of emerging multi-site resistance.

Forward-Looking Considerations

• Climate and resistance: Larger pathogen populations during warmer seasons and stress-triggered sexual recombination can increase genetic variation, accelerating adaptive responses. Surveillance should accordingly be season- and climate-aware.
• Decision support: Integrate dose optimization, interval planning, and weather-based risk into spray programs; pair with host resistance and cultural controls to reduce selection pressure.
• Research gaps: Field-scale confirmation of reversibility windows, quantitative fitness-cost curves, and validated molecular markers for early detection will sharpen resistance stewardship.

Limitations (for interpretation)

• Lab system: Agar-plate evolution under controlled conditions may not capture all field complexities (microclimate, canopy coverage, spray deposition, mixed chemistries).
• Chemistry scope: Findings relate to mancozeb (multi-site). Extrapolation to other multi-site fungicides should be hypothesis-driven and tested.
• Time horizon: The 400-day window demonstrates reversibility in this study; longer-term stability (multi-year in field) remains to be characterized.