Bacteria evolve resistance to antimicrobials secreted by other bacteria and fungi and gain fitness advantage in their natural habitat. Anthropogenic activities typically increase the level of antibiotics in the environment and exaggerate the magnitude of this fitness advantage, thus selecting for bacteria that carry resistance. But the evolution of resistance is a natural process and has been shown to occur even in the absence of any antibiotic in the environment. We study such de novo resistance evolution in complex, and sometimes fluctuating, environments. Of particular interest are the antimicrobials that are termed as alternatives to antibiotics. We know little about the potential of bacteria to evolve de novo resistance against these alternatives. We investigate this potential, its molecular underpinnings as well as cross-resistance profiles of bacteria using experimental evolution. Â