A reporter system for detection of protein-protein interactions in the periplasm of a bacterial host cell, said system comprising: a first expression system comprising: a nucleic acid molecule encoding an alpha (α) fragment of a β-lactamase reporter protein molecule; a nucleic acid molecule encoding a first signal sequence; and a nucleic acid molecule encoding a first member of a putative binding pair, wherein said nucleic acid molecule encoding the alpha (α) fragment, said nucleic acid molecule encoding the first signal sequence, and said nucleic acid molecule encoding the first member of the putative binding pair are operatively coupled to permit their expression in a bacterial host cell as a first fusion protein and a second expression system comprising: a nucleic acid molecule encoding an omega (ω) fragment of the β-lactamase reporter protein molecule; a nucleic acid molecule encoding a second signal sequence; and a nucleic acid molecule encoding a second member of the putative binding pair, wherein said nucleic acid molecule encoding the omega (ω) fragment, said nucleic acid molecule encoding the second signal sequence, and said nucleic acid molecule encoding the second member of the putative binding pair are operatively coupled to permit their expression in a bacterial host cell as a second fusion protein, wherein the first and the second fusion proteins and the first and the second signal sequences are selected so that at least one of the first and the second signal sequences directs co-translational transport of at least one of the fusion proteins, when expressed in a bacterial host cell, into the host cell periplasm where, when present, the first and second members of the putative binding pair bind together and the alpha (α) and omega (ω) fragments of the β-lactamase reporter protein molecule are reconstituted, thereby producing an active β-lactamase reporter protein; wherein the bacterial host cell is a gram negative bacteria. a first expression system comprising: a nucleic acid molecule encoding an alpha (α) fragment of a β-lactamase reporter protein molecule; a nucleic acid molecule encoding a first signal sequence; and a nucleic acid molecule encoding a first member of a putative binding pair, wherein said nucleic acid molecule encoding the alpha (α) fragment, said nucleic acid molecule encoding the first signal sequence, and said nucleic acid molecule encoding the first member of the putative binding pair are operatively coupled to permit their expression in a bacterial host cell as a first fusion protein and a nucleic acid molecule encoding an alpha (α) fragment of a β-lactamase reporter protein molecule; a nucleic acid molecule encoding a first signal sequence; and a nucleic acid molecule encoding a first member of a putative binding pair, wherein said nucleic acid molecule encoding the alpha (α) fragment, said nucleic acid molecule encoding the first signal sequence, and said nucleic acid molecule encoding the first member of the putative binding pair are operatively coupled to permit their expression in a bacterial host cell as a first fusion protein and a second expression system comprising: a nucleic acid molecule encoding an omega (ω) fragment of the β-lactamase reporter protein molecule; a nucleic acid molecule encoding a second signal sequence; and a nucleic acid molecule encoding a second member of the putative binding pair, wherein said nucleic acid molecule encoding the omega (ω) fragment, said nucleic acid molecule encoding the second signal sequence, and said nucleic acid molecule encoding the second member of the putative binding pair are operatively coupled to permit their expression in a bacterial host cell as a second fusion protein, wherein the first and the second fusion proteins and the first and the second signal sequences are selected so that at least one of the first and the second signal sequences directs co-translational transport of at least one of the fusion proteins, when expressed in a bacterial host cell, into the host cell periplasm where, when present, the first and second members of the putative binding pair bind together and the alpha (α) and omega (ω) fragments of the β-lactamase reporter protein molecule are reconstituted, thereby producing an active β-lactamase reporter protein; a nucleic acid molecule encoding an omega (ω) fragment of the β-lactamase reporter protein molecule; a nucleic acid molecule encoding a second signal sequence; and a nucleic acid molecule encoding a second member of the putative binding pair, wherein said nucleic acid molecule encoding the omega (ω) fragment, said nucleic acid molecule encoding the second signal sequence, and said nucleic acid molecule encoding the second member of the putative binding pair are operatively coupled to permit their expression in a bacterial host cell as a second fusion protein, wherein the first and the second fusion proteins and the first and the second signal sequences are selected so that at least one of the first and the second signal sequences directs co-translational transport of at least one of the fusion proteins, when expressed in a bacterial host cell, into the host cell periplasm where, when present, the first and second members of the putative binding pair bind together and the alpha (α) and omega (ω) fragments of the β-lactamase reporter protein molecule are reconstituted, thereby producing an active β-lactamase reporter protein; wherein the bacterial host cell is a gram negative bacteria.