Genome-Based Retrospective Analysis of a Providencia stuartii Outbreak in Rome, Italy: Broad Spectrum IncC Plasmids Spread the NDM Carbapenemase within the Hospital

Abstract

Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Whole-genome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the blaNDM-1 metallo-β-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most β-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment.

Genomic epidemiology and heterogeneity of Providencia and their bla NDM-1 -carrying plasmids

“…On the one hand, we identified five Inc groups of bla NDM-1 -carrying plasmids namely IncC [ 21 ], IncW [ 41 , 55 ], Inc pCHS4.1-3 , Inc pPROV114-NR , and Inc pPrY2001 , among which the last three were newly designated. IncC plasmids are mostly prevalent among Providencia , which is consistent with the previous study [ 21 , 22 ]. All these five Inc groups of bla NDM-1 -carrying plasmids contain the complete conjugation regions, which would accelerate the spread of bla NDM-1 within Providencia and to other bacteria [ 21 , 37 , 40 , 56 , 57 ].…”

“…Compared to the Providencia isolates from other countries, the Chinese isolates presented significantly higher resistance gene ratios in C01.S01 ( P -value = 0.0041) and C01.S02 ( P -value = 0.0015) (Figure S3), indicating different resistance-gene prevalence profiles between China and other countries [ 22 , 39 , 40 ]. Providencia strains harboured abundant antimicrobial resistance genes and might serve as reservoirs for resistance genes, exacerbating the spread of resistance genes among different bacteria.…”

“…It has been revealed that the frequent emergence of carbapenemase-producing Providencia strains is mainly due to the spread of bla NDM-1 gene [ 2 , 20 ]. IncC plasmids that carry bla NDM-1 have been widely detected in P. stuartii from distrust Romanian [ 21 ] and Italy hospitals [ 22 ], and several additional Inc (incompatible) groups of bla NDM-1 -harbouring plasmids have been identified in Providencia [ 18 , 23–26 ], indicating diverse types of plasmids contribute to the spread of bla NDM-1 in Providencia . However, a genomic view of the dissemination of bla NDM-1 -carrying plasmids among a large collection of Providencia strains is lacking.…”

Genomic revisitation and reclassification of the genus Providencia

“…Antibiotic resistance has been documented in various degrees among Providencia species in clinical settings ( 34 , 35 ). In an effort to understand the landscape of antibiotic-resistance genes (ARGs) in the Providencia genomes, we performed an analysis on 545 strains, primarily sourced from public databases.…”

Genome-Wide Exploration of the OpportunisticProvidencia stuartiiUnveils the Novel Genetic Interactions with the Virulence Gene of Diarrheal Pathogens

“…Following its emergence, P. stuartii led to numerous outbreaks documented in Brazil, China, Taiwan and Tunisia. Predominantly reported cases were within hospital facilities, particularly in intensive care units (ICUs), long-term care facilities (LTCFs), and burn units [24][25][26][27][28][29][30].…”