Learn Spanish (Latin America): Con este trabajo extenuante, el sudor le molesta a uno. - With this grueling work, the sweat bothers one.

Because uno is the indirect object of the sentence, not the subject. The verb molestar works like gustar: el sudor (the sweat) is the subject doing the bothering to "one". When uno is the object receiving the action, it requires the preposition a, becoming a uno.

Why is there a le before molesta if we already specify a uno?

In Spanish, when an indirect object is explicitly stated using a (like a uno), you generally must include the matching indirect object pronoun before the verb. Since uno is grammatically third-person singular, we need the pronoun le.

If a woman is speaking, would she say a una instead of a uno?

Yes! While uno is often used as a generic default by people of any gender, female speakers will frequently use una (as in le molesta a una) to make a generic statement that still connects to their own perspective.

Why is the verb molesta singular if "grueling work" implies a lot of intense effort?