The primary weakness of the infection as a whole (generally Spore Mobs and Blocks) is cold temperatures. Most spore-related things are affected in some way, but the primary facet is Mobs (excluding most Utility Abnormal besides Evoker Claws, Hexenmeister Claws, and Tentacles). This weakness is mainly facilitated though vanilla Minecraft freezing (present in the base game) and the Frostbite Effect (introduced by the mod).
Besides Powdered Snow, Spore Mobs will start freezing when hit by a Snowball. When Spore Mobs are freezing, they'll function like most mobs do when freezing; visibly shiver and take damage over time. Spore Mobs take x5 damage from freeze damage (5 damage (x2.5 hearts)). Additionally, they're unable to spawn a Scent upon death. Furthermore, some specific Mobs will have unique ailments when freezing:
The passive regeneration of Organoids is disabled.
Linked Mounds at Age 4 will be unable to send a Signal to a Proto Hivemind upon death.
Upon Infected, Evolved, Hyper Evolved, Experiments, Bairns, Scampers, and Gastgebers dying due to freeze damage, they have a chance to place Frozen Remains upon death.
An Infected Human shivering and freezing to death in a Frozen River.
The Frostbite Effect acts as a representation for a Spore Mob being ailed by frigid temperatures. When Spore Mobs have Frostbite, basic Evolution and Hyper Evolution timers will be paused until they no longer have Frostbite. Mobs are also damaged overtime, with the damage dealt being dynamic. This is fully explained on the Effects page in the Frostbite section.
Furthermore, if a biome is considered 'cold' (has an internal temperature value of 0.2 or lower), Spore Mobs will be unable to spawn naturally in said biome. This does not account for any cave biomes beneath the surface biome (Dripstone Caves, Lush Caves, etc.). If any Infected, Evolved, Hyper Evolved, Experiments, Bairns, Scampers, and Gastgebers do find themselves in a cold biome, they'll continually be given Frostbite. Below is a list of biomes that affect Spore Mobs:
Any modded biomes with a low enough temperature value
The infection's weakness to the cold can be exploited by players via C.D.U.s and P.C.I.s, fueled by Ice Canisters. C.D.U.s are extremely useful, being capable of giving nearby Spore Mobs increasing amplifiers of Frostbite, destroying Spore Foliage, un-infesting Infested Blocks, despawning Scents and Tendrils, and more. P.C.I.s are used to inject frigid liquid directly into Spore Mobs, giving them Frostbite V and even un-Linking them (if applicable). More info is available on their respective pages. The Cryogenic Aspect Enchantment is also effective at exploiting the Spore's cold weakness; it can be put on Spore Weapons (excluding Bioguns) via a Cryogenic Reagent. Weapons Enchanted with Cryogenic Aspect will, upon hitting living entities, cause them to freeze for 15 seconds.