Emergence and Evolution of Unique Plasmids Harboring
 bla
 IMP-70
 and
 bla
 CTX-M-253
 in Multidrug-Resistant Providencia rettgeri

Watanabe, Mako; Nakano, Ryuichi; Tanouchi, Ayako; Nakano, Akiyo; Suzuki, Yuki; Saito, Kai; Sakata, Ryuji; Ogawa, Miho; Yano, Hisakazu

doi:10.1128/spectrum.01204-22

Cited by 4 publications

(1 citation statement)

References 24 publications

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“…bla IMP-70 and bla CTX-M-253 in multidrug-resistant Providencia Rettgeri and suggested that the cointegration of plasmids in P . rettgeri may not be unusual and may play a role in the transmission of clinically relevant b-lactamases ( Watanabe et al, 2022 ). In our study, one class 1 integron was identified in p18004577_NDM, which harbored multiple resistance genes, such as bla O XA -10 , ant ( 2′ ) -Ia , catB8 , bla PER-4 , and two Δsul1 .…”

Section: Discussionmentioning

confidence: 99%

Conjugation of plasmid harboring blaNDM-1 in a clinical Providencia rettgeri strain through the formation of a fusion plasmid

Zhang

Wang

et al. 2023

Front. Microbiol.

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Providencia rettgeri has recently gained increased importance owing to the New Delhi metallo-β-lactamase (NDM) and other β-lactamases produced by its clinical isolates. These enzymes reduce the efficiency of antimicrobial therapy. Herein, we reported the findings of whole-genome sequence analysis and a comprehensive pan-genome analysis performed on a multidrug-resistant P. rettgeri 18004577 clinical strain recovered from the urine of a hospitalized patient in Shandong, China, in 2018. Providencia rettgeri 18004577 was found to have a genome assembly size of 4.6 Mb with a G + C content of 41%; a circular plasmid p18004577_NDM of 273.3 Kb, harboring an accessory multidrug-resistant region; and a circular, stable IncT plasmid p18004577_Rts of 146.2 Kb. Additionally, various resistance genes were identified in its genome, including blaNDM-1, blaOXA-10, blaPER-4, aph(3′)-VI, ant(2′′)-Ia, ant(3′)-Ia, sul1, catB8, catA1, mph(E), and tet. Conjugation experiments and whole-genome sequencing revealed that the blaNDM-1 gene could be transferred to the transconjugant via the formation of pJ18004577_NDM, a novel hybrid plasmid. Based on the genetic comparison, the main possible formation process for pJ18004577_NDM was the insertion of the [ΔISKox2-IS26-ΔISKox2]-aph(3′)-VI-blaNDM-1 translocatable unit module from p18004577_NDM into plasmid p18004577_Rts in the Russian doll insertion structure (ΔISKox2-IS26-ΔISKox2), which played a role similar to that of IS26 using the “copy-in” route in the mobilization of [aph(3′)-VI]-blaNDM-1. The array, multiplicity, and diversity of the resistance and virulence genes in this strain necessitate stringent infection control, antibiotic stewardship, and periodic resistance surveillance/monitoring policies to preempt further horizontal and vertical spread of the resistance genes. Roary analysis based on 30 P. rettgeri strains pan genome identified 415 core, 756 soft core, 5,744 shell, and 12,967 cloud genes, highlighting the “close” nature of P. rettgeri pan-genome. After a comprehensive pan-genome analysis, representative biological information was revealed that included phylogenetic distances, presence or absence of genes across the P. rettgeri bacteria clade, and functional distribution of proteins. Moreover, pan-genome analysis has been shown to be an effective approach to better understand P. rettgeri bacteria because it helps develop various tailored therapeutic strategies based on their biological similarities and differences.

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Section: Discussionmentioning

confidence: 99%

Conjugation of plasmid harboring blaNDM-1 in a clinical Providencia rettgeri strain through the formation of a fusion plasmid

Zhang

Wang

et al. 2023

Front. Microbiol.

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Identification of a novel Providencia species showing multi-drug-resistant in three patients with hospital-acquired infection

Yang,

Chen,

Yang

et al. 2024

International Journal of Antimicrobial Agents

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Identification and Functional Annotation of Hypothetical Proteins of Pan-Drug-Resistant Providencia rettgeri Strain MRSN845308 Toward Designing Antimicrobial Drug Targets

Pal,

Anik,

Rahman

et al. 2024

Bioinform Biol Insights

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Providencia rettgeri has increasingly been responsible for several infections, including urinary tract, post-burn wounds, neonatal sepsis, and others. The emergence of drug-resistant isolates of P rettgeri, accompanied by intrinsic and acquired antibiotic resistance, has exacerbated the challenge of treating such infections, necessitating the development of novel therapeutics. Hypothetical proteins (HPs) form a major portion of cellular proteins and can be targeted by these novel therapeutics. In this study, 410 HPs from a pan-drug-resistant (PDR) P rettgeri strain (MRSN845308) were functionally annotated and characterized by physicochemical properties, localization, virulence, essentiality, druggability, and functionality. Among 410 HPs, the VirulentPred 2.0 tool and VICMpred combinedly predicted 33 HPs as virulent, whereas 48 HPs were highly interacting proteins based on the STRING v12 database. BlastKOALA and eggNOG-mapper v2.1.12 predicted 13 HPs involved in several metabolic pathways like Riboflavin metabolism and Lipopolysaccharide biosynthesis. Overall, 83 HPs were selected as primary drug targets; however, only 80 remained after nonhomology searching and essentiality analysis. In addition, all were detected as novel drug targets according to DrugBank 5.1.12. Considering the potential of membrane and extracellular proteins, 29 HPs (extracellular, outer, and inner membrane) were selected based on the combined prediction from PSORTb v3.0.3, CELLO v.2.5, BUSCA, SOSUIGramN, and PSLpred. According to the prevalence of those HPs in different strains of P rettgeri sequences in National Center for Biotechnology Information Identical Protein Groups (NCBI-IPG), 5 HPs were selected as final drug targets. In addition, 5 other HPs annotated as transporter proteins were also added to the list. As no crystal structures of our targets are present, 3-dimensional structures of selected HPs were predicted by the AlphaFold Server powered by AlphaFold 3. Our findings might facilitate a better understanding of the mechanism of virulence and pathogenesis, and up-to-date annotations can make uncharacterized HPs easy to identify as targets for novel therapeutics.

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Emergence and Evolution of Unique Plasmids Harboring bla _IMP-70 and bla _CTX-M-253 in Multidrug-Resistant Providencia rettgeri

Cited by 4 publications

References 24 publications

Conjugation of plasmid harboring blaNDM-1 in a clinical Providencia rettgeri strain through the formation of a fusion plasmid

Conjugation of plasmid harboring blaNDM-1 in a clinical Providencia rettgeri strain through the formation of a fusion plasmid

Identification of a novel Providencia species showing multi-drug-resistant in three patients with hospital-acquired infection

Identification and Functional Annotation of Hypothetical Proteins of Pan-Drug-Resistant Providencia rettgeri Strain MRSN845308 Toward Designing Antimicrobial Drug Targets

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Emergence and Evolution of Unique Plasmids Harboring bla IMP-70 and bla CTX-M-253 in Multidrug-Resistant Providencia rettgeri

Cited by 4 publications

References 24 publications

Conjugation of plasmid harboring blaNDM-1 in a clinical Providencia rettgeri strain through the formation of a fusion plasmid

Conjugation of plasmid harboring blaNDM-1 in a clinical Providencia rettgeri strain through the formation of a fusion plasmid

Identification of a novel Providencia species showing multi-drug-resistant in three patients with hospital-acquired infection

Identification and Functional Annotation of Hypothetical Proteins of Pan-Drug-Resistant Providencia rettgeri Strain MRSN845308 Toward Designing Antimicrobial Drug Targets

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Emergence and Evolution of Unique Plasmids Harboring bla _IMP-70 and bla _CTX-M-253 in Multidrug-Resistant Providencia rettgeri