Acinetobacter baumannii is an opportunistic pathogen emerging as a major health threat in clinical and community settings worldwide. Comparative genome analysis of Acinetobacter spp. highlights the presence of many genomic islands (GIs), i.e. distinct regions of novelty acquired through lateral transfer. These GIs appear to encode adaptive traits implicated in properties such as virulence, pathogenicity and drug resistance in A. baumannii. 

Through access to some of the first Australian isolates of this gram-negative bacillus, I have identified GIs resident within community and clinical strains. As GI components tend to display highly novel protein sequences, their tertiary structure determination and subsequent fold recognition proves key to annotation of function. From 87 islands, 125 target sequences were selected as appropriate for structure determination in a high-throughput pipeline. 

I outline details for two crystal structures solved. The structure of A. baumannii epimerase WbjB (2.65 Å) reveals an enzyme of the extended short chain dehydrogenase/reductase (SDR) family in an unusual hexameric form, with cofactor NADP bound. The GI from which the enzyme derives clearly encodes discrete steps of lipopolysaccharide biosynthesis, so likely influencing virulence factors for its host pathogen. A second crystal structure, SDR-WM99c (2.4 Å) also proved to be an SDR enzyme, in this case of classical subtype. This structure shows homology to a group of uncharacterized dehydrogenase/ reductases appearing across several microbial organisms. The recurrence of the SDR family within my target pool signifies that the highly diverse substrates accommodated by this enzyme group generate diverse functions that are powerful adaptive features for pathogenic Acinetobacter spp.