Background: Enterobacter is a major nosocomial genus of Enterobacteriaceae responsible for a variety of nosocomial infections, particularly in prolonged hospitalized patients in the intensive care units. Since current antibiotics have failed treating colistin- and carbapenem-resistant Enterobacteriaceae, efforts are underway to find suitable alternative strategies. Therefore, this study conducted a reverse vaccinology (RV) to identify novel and putative immunogenic targets using core proteome of 20 different sequence types (STs) of clinical Enterobacter spp. Moreover, we introduced a structural-based approach for exploration of potential vaccine candidates against the Enterobacteriaceae family using their conserved domain analysis.

Results: A number of 2616 core coding sequences (CDSs) were retrieved from 20 clinical strains of Enterobacter spp. with a similarity of ≥ 50%. Nine proteins with a score of ≥ 20 considered as the shortlisted proteins based on the quartile scoring method, including three TonB-dependent receptors, WP_008500981.1, WP_058690971.1 and WP_058679571.1; one YjbH domain-containing protein, WP_110108068.1; three flagellar proteins, WP_088207510.1, WP_033145204.1 and WP_058679632.1; one spore-coat U domain-containing protein, WP_039266612.1; and one DD-metalloendopeptidase family protein, WP_025912449.1. In this study, proteins WP_058690971.1 and WP_110108068.1 were detected as the top candidates with regard to immune stimulation and interactions with TLRs. However, their efficacy is remaining to be evaluated experimentally.

Conclusions: Our investigation introduced common ferrichrome porins with high sequence similarity as potential vaccine candidates against the Enterobacteriaceae family. These proteins belong to the iron acquisition system and possess all criteria of suitable vaccine targets. Therefore, they need to be specifically paid attention for vaccine development against clinically important members of Enterobacteriaceae family.