Genome-based analyses from four clinically-isolated strains refined the taxonomy of Proteus genomosp. 6 and revealed their underestimated role in gastrointestinal diseases.

Background: Proteus spp. have long been recognized for their role in urinary tract infections, while recent evidence disclosed their implications in gastrointestinal diseases. Despite this, the taxonomy of clinically-derived Proteus spp., particularly those from gastrointestinal samples, remains understudied and is frequently mis-assigned, which limits our understanding of infections caused by these species.

Results: Four Proteus strains (i.e., DFP240708, LHD240705, TSJ240517 and WDL240414) were isolated from the appendiceal pus of patients with acute appendicitis, whole-genome average nucleotide identity (ANI) analysis identified all of them as Proteus genomosp. 6, different from that identified using the automated bacterial identification instrument (VITEK^®-32). Based on ANI and the core-genomic phylogenetic tree, we found that 87.5% of clinically-related strains previously identified as P. columbae should be re-classified as Proteus genomosp. 6. Additionally, the Proteus genomosp. 6 genomes all carry one or more beta-lactam resistance genes, but none carry aminoglycoside resistance genes, and antibiotic susceptibility testing conducted on the four strains isolated in this study confirmed these findings. Among the genomes analyzed, only four (two from this study (TSJ240517 and WDL240414)) carried virulence genes, specifically the hlyA, hlyB, and hlyD genes encoding hemolysin.

Conclusion: Our study highlights inaccuracies in the taxa classification of Proteus species under clinical settings, underscoring the necessity of using genomic-based taxonomic assignment methods. We revealed that the prevalence of Proteus genomosp. 6 in clinical infections has likely been underestimated. Furthermore, given the resistance-gene absence and their sensitivity to aminoglycosides, aminoglycosides may serve as a promising first-line treatment option for infections caused by this species.