AUTHOR=Huang Zhenzhou , Zhang Guozhong , Zheng Zhibei , Lou Xiuqin , Cao Feifei , Zeng Lingyi , Wang Duochun , Yu Keyi , Li Jun 

TITLE=Genomic insights into the evolution, pathogenicity, and extensively drug-resistance of emerging pathogens Kluyvera and Phytobacter

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1376289

DOI=10.3389/fcimb.2024.1376289

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p><italic>Kluyvera</italic> is a Gram-negative, flagellated, motile bacillus within the <italic>Enterobacteriaceae</italic>. The case reports of clinical infections shed light on the importance of this organism as an emerging opportunistic pathogen. The genus <italic>Phytobacter</italic>, which often be misidentified with <italic>Kluyvera</italic>, is also an important clinically relevant member of the <italic>Enterobacteriaceae</italic>. However, the identification of <italic>Kluyvera</italic> and <italic>Phytobacter</italic> is problematic, and their phylogenetic relationship remains unclear.</p></sec><sec><title>Methods</title><p>Here, 81 strains of <italic>Kluyvera</italic> and 16 strains of <italic>Phytobacter</italic> were collected. A series of comparative genomics approaches were applied to the phylogenetic relationship reconstruction, virulence related genes profiles description, and antibiotic resistance genes prediction.</p></sec><sec><title>Results</title><p>Using average nucleotide identity (ANI) and <italic>in silico</italic> DNA-DNA hybridization (<italic>is</italic>DDH), we offered reliable species designations of 97 strains, in which 40 (41.24%) strains were incorrectly labeled. A new <italic>Phytobacter</italic> genomospecies-1 were defined. <italic>Phytobacter</italic> and <italic>Kluyvera</italic> show great genome plasticity and inclusiveness, which may be related to their diverse ecological niches. An intergenomic distances threshold of 0.15875 was used for taxonomy reassignments at the phylogenomic-group level. Further principal coordinates analysis (PCoA) revealed 11 core genes of <italic>Kluyvera</italic> (<italic>pelX, mdtL, bglC, pcak-1, uhpB, ddpA-2, pdxY, oppD-1, cptA, yidZ, csbX</italic>) that could be served as potential identification targets. Meanwhile, the <italic>Phytobacter</italic> specific virulence genes <italic>clbS, csgA-C, fliS, hsiB1_vipA and hsiC1_vipB</italic>, were found to differentiate from <italic>Kluyvera</italic>. We concluded that the evolution rate of <italic>Kluyvera</italic> was 5.25E-6, approximately three times higher than that of <italic>Phytobacter</italic>. Additionally, the co-existence of ESBLs and carbapenem resistance genes were present in approximately 40% strains, suggesting the potential development of extensively drug-resistant or even fully drug-resistant strains.</p></sec><sec><title>Discussion</title><p>This work provided a better understanding of the differences between closely related species <italic>Kluyvera</italic> and <italic>Phytobacter</italic>. Their genomes exhibited great genome plasticity and inclusiveness. They not only possess a potential pathogenicity threat, but also a risk of multi-drug resistance. The emerging pathogens <italic>Kluyvera</italic> and <italic>Phytobacter</italic> warrant close attention.</p></sec>