The present invention relates to methods of treating Mycobacterium pathogen infection in a subject that involve: inhibiting proteasomal activity in a pathogen under conditions effective to make the pathogen susceptible to antibacterial host defenses; inhibiting enzyme activity in a pathogen under conditions effective to make the pathogen susceptible to antibacterial host defenses, where the enzyme is a DNA repair enzyme or a flavin-like co-factor synthesis enzyme, or inhibiting proteasomal and enzyme activity under conditions to make the pathogen susceptible to antibacterial host defenses. The present invention also relates to methods for screening compounds that inhibit proteasomal and protease activity, DNA repair enzyme activity, or flavin-like co-factor synthesis enzyme activity, where the inhibitory compounds have an ability to sensitize bacteria to the antibacterial effects of oxidative/nitrosative stress.