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In New Orleans, earthquakes caused by fracking unleash giant spiders. Various groups, including bus driver Charlie and his passengers, his family on a city tour, and swamp tour guide Paul, face the arachnid onslaught. Katelynn, a biologist, realizes the spiders operate as a hive mind and suggests killing the queen to stop them. Amidst chaos and sacrifices, they embark on a perilous mission to eradicate the queen and survive the spider-infested city.